semaglutide (Ozempic, Rybelsus, Wegovy)

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Indications

* > 1/2 of all adults in the U.S. are eligible for semaglutide[54]

* semaglutide improves HgbA1c more than canagliflozin 1.5 vs 1.0%[8]

Contraindications

Dosage

  • 0.25 mg SC once weekly for 4 weeks, then increase to 0.5 mg once weekly
  • if glycemic control is not achieved after at least 4 weeks on 0.5-mg dose, the dose may be increased to 1 mg once weekly
  • 2.4-mg dose weekly induces weight reduction of 10% of body weight in patients with type-2 diabetes[13]
  • 7.2 mg superior to 24 mg for bodyweight reduction in adults with obesity[74]

Adverse effects

* not such association was found with liraglutide[44]

Mechanism of action

Clinical trials

  • 6 months, almost all participants achieved 5% weight loss, 1/2 lost >10%, & a 1/4 lost >15% of their body weight[16]
  • STEP 1 & STEP 4 trials:[14][48]
    • 1 year after withdrawal of once-weekly subcutaneous semaglutide 2.4 mg & lifestyle intervention, participants regained 2/3 of their prior weight loss, with similar changes in cardiometabolic measures[48]

Notes

  • cost $10,000 annually (2019)
  • cost for Wegovy (weight loss) is $1349 for 4 weekly injections[19]
  • Novo Nordisk has not announced pricing on oral semiglutide
  • the price of Wegovy would need to be cut by over 80% to $127/month to become costs effective[61]

More general terms

Component of

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 Marso SP, Bain SC, Consoli A et al Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. September 16, 2016 <PubMed> PMID: https://pubmed.ncbi.nlm.nih.gov/27633186 Free Article <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1607141
  2. ↑ 2.0 2.1 2.2 Sorli S, Harashima SI, Tsoukas GM et al Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes (SUSTAIN 1): a double-blind, randomised, placebo-controlled, parallel-group, multinational, multicentre phase 3a trial. Lancet Diabetes & Endocrinology. Jan 16, 2017 <PubMed> PMID: https://pubmed.ncbi.nlm.nih.gov/28110911 <Internet> http://www.thelancet.com/journals/landia/article/PIIS2213-8587(17)30013-X/fulltext
    Scheen AJ Semaglutide: a promising new glucagon-like peptide-1 receptor agonist. Lancet Diabetes & Endocrinology. Jan 16, 2017 <PubMed> PMID: https://pubmed.ncbi.nlm.nih.gov/28110912 <Internet> http://www.thelancet.com/journals/landia/article/PIIS2213-8587(17)30012-8/fulltext (industry-funded study)
    Novo Nordisk News Release. Dec. 5, 2016 Novo Nordisk Files for Regulatory Approval of Once-Weekly Semaglutide with the FDA for the Treatment of Type 2 Diabetes. http://press.novonordisk-us.com/2016-12-05-Novo-Nordisk-Files-for-Regulatory-Approval-of-Once-Weekly-Semaglutide-with-the-FDA-for-the-Treatment-of-Type-2-Diabetes
  3. ↑ 3.0 3.1 Frieden J FDA Panel Urges Approval of Semaglutide for T2D. Vote was 16-0 with one abstention. MedPage Today. October 18, 2017 https://www.medpagetoday.com/Endocrinology/Diabetes/68642
    Tucker ME FDA Approves Semaglutide for Type 2 Diabetes Medscape - Dec 05, 2017. https://www.medscape.com/viewarticle/889631
    Windle ML. FDA New Drug and Biologic Approvals -- 2017 Year-in-Review Medscape - Jan 11, 2018. https://reference.medscape.com/viewarticle/890871
    U.S. Food and Drug Administration. Novel Drug Approvals for 2017. https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DrugInnovation/ucm537040.htm
  4. ↑ 4.0 4.1 4.2 Pratley RE, Aroda VR, Lingvay I et al Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial. Lancet Diabetes & Endocrinology. Jan 31, 2018 <PubMed> PMID: https://pubmed.ncbi.nlm.nih.gov/29397376 <Internet> http://www.thelancet.com/journals/landia/article/PIIS2213-8587(18)30024-X/abstract
    Tahrani AA, Bellary S, Barnett AH. Once-weekly GLP-1R agonists: moving the goal posts. Lancet Diabetes & Endocrinology. Jan 31, 2018 <PubMed> PMID: https://pubmed.ncbi.nlm.nih.gov/29397375 <Internet> http://www.thelancet.com/journals/landia/article/PIIS2213-8587(18)30049-4/fulltext
  5. ↑ 5.0 5.1 Rosenstock J, Allison D, Birkenfeld AL et al Effect of Additional Oral Semaglutide vs Sitagliptin on Glycated Hemoglobin in Adults With Type 2 Diabetes Uncontrolled With Metformin Alone or With SulfonylureaThe PIONEER 3 Randomized Clinical Trial. JAMA. 2019;321(15):1466-1480. https://jamanetwork.com/journals/jama/fullarticle/2729339
  6. ↑ 6.0 6.1 Husain M, Birkenfeld AL, Donsmark M et al. Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med 2019 Jun 11 PMID: https://pubmed.ncbi.nlm.nih.gov/31185157 https://www.nejm.org/doi/10.1056/NEJMoa1901118
  7. ↑ 7.0 7.1 Pratley R, Amod A, Hoff ST et al. Oral semaglutide versus subcutaneous liraglutide and placebo in type 2 diabetes (PIONEER 4): A randomised, double-blind, phase 3a trial. Lancet 2019 Jul 6; 394:39. PMID: https://pubmed.ncbi.nlm.nih.gov/31186120 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31271-1/fulltext
    Holst JJ. Which to choose, an oral or an injectable glucagon-like peptide-1 receptor agonist? Lancet 2019 Jul 6; 394:4. PMID: https://pubmed.ncbi.nlm.nih.gov/31186119 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31350-9/fulltext
  8. ↑ 8.0 8.1 Lingvay I, Catarig AM, Frias JP et al Efficacy and safety of once-weekly semaglutide versus daily canagliflozin as add-on to metformin in patients with type 2 diabetes (SUSTAIN 8): a double-blind, phase 3b, randomised controlled trial. Lancet Diabetes & Endocrinology. Sept 17, 2019 PMID: https://pubmed.ncbi.nlm.nih.gov/3154086 https://www.thelancet.com/journals/landia/article/PIIS2213-8587(19)30311-0/fulltext
    Scheen AJ SGLT2 inhibitor or GLP-1 receptor agonist in type 2 diabetes? Lancet Diabetes & Endocrinology. Sept 17, 2019 PMID: https://pubmed.ncbi.nlm.nih.gov/31540866 https://www.thelancet.com/journals/landia/article/PIIS2213-8587(19)30310-9/fulltext
  9. ↑ 9.0 9.1 Tucker ME FDA OKs 'Game-Changer' Oral GLP-1 Agonist for Type 2 Diabetes. Medscape - Sep 20, 2019. https://www.medscape.com/viewarticle/918772
  10. ↑ 10.0 10.1 10.2 Newsome PN, Buchholtz K, Cusi K et al A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis. N Engl J Med. 2020 Nov 13. PMID: https://pubmed.ncbi.nlm.nih.gov/33185364 https://www.nejm.org/doi/full/10.1056/NEJMoa2028395
  11. ↑ 11.0 11.1 Wilding JPH, Batterham RL, Calanna S et al Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl H Med. 2021. Feb 10 PMID: https://pubmed.ncbi.nlm.nih.gov/33567185 https://www.nejm.org/doi/full/10.1056/NEJMoa2032183
    Ingelfinger JR, Rosen CJ STEP 1 for Effective Weight Control - Another First Step? N Engl H Med. 2021. Feb 10 PMID: https://pubmed.ncbi.nlm.nih.gov/33567184 https://www.nejm.org/doi/full/10.1056/NEJMe2101705
  12. ↑ 12.0 12.1 Wadden TA, Bailey TS, Billings LK et al. Effect of subcutaneous semaglutide vs placebo as an adjunct to intensive behavioral therapy on body weight in adults with overweight or obesity: The STEP 3 randomized clinical trial. JAMA 2021 Feb 24:e211831 PMID: https://pubmed.ncbi.nlm.nih.gov/33625476 PMCID: PMC7905697 Free PMC article https://jamanetwork.com/journals/jama/fullarticle/2777025
  13. ↑ 13.0 13.1 Davies M, Faerch L, Jeppesen OK, et al. Semaglutide 2 4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): A randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. Lancet 2021 Mar 2; [e-pub]. PMID: https://pubmed.ncbi.nlm.nih.gov/33667417 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00213-0/fulltext
  14. ↑ 14.0 14.1 14.2 14.3 Rubino D, Abrahamsson N, Davies M et al Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity. The STEP 4 Randomized Clinical Trial. JAMA. Published online March 23, 2021 PMID: https://pubmed.ncbi.nlm.nih.gov/33755728 https://jamanetwork.com/journals/jama/fullarticle/2777886
  15. ↑ 15.0 15.1 Busko M FDA Approves 'Gamechanger' Semaglutide for Weight Loss. Medscape - Jun 04, 2021. https://www.medscape.com/viewarticle/952441
  16. ↑ 16.0 16.1 Ghusn W et al. Weight loss outcomes associated with semaglutide treatment for patients with overweight or obesity. JAMA Netw Open 2022 Sep 19; 5:e2231982. PMID: https://pubmed.ncbi.nlm.nih.gov/36121652 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2796491
  17. ↑ 17.0 17.1 Perreault L et al. Changes in glucose metabolism and glycemic status with once-weekly subcutaneous semaglutide 2.4 mg among participants with prediabetes in the STEP program. Diabetes Care 2022 Oct; 45:2396 PMID: https://pubmed.ncbi.nlm.nih.gov/35724304 https://diabetesjournals.org/care/article/45/10/2396/147113/Changes-in-Glucose-Metabolism-and-Glycemic-Status
  18. ↑ 18.0 18.1 Weghuber D et al. Once-weekly semaglutide in adolescents with obesity. N Engl J Med 2022 Nov 2; [e-pub] PMID: https://pubmed.ncbi.nlm.nih.gov/36322838 https://www.nejm.org/doi/10.1056/NEJMoa2208601
  19. ↑ 19.0 19.1 AMA Morning Rounds. Dec 5, 2022 American Medical Society
  20. ↑ 20.0 20.1 20.2 Nainggolan L FDA Approves Wegovy (Semaglutide) for Obesity in Teens 12 and Up. Medscape. January 03, 2023 https://www.medscape.com/viewarticle/986403
  21. ↑ 21.0 21.1 Medical Knowledge Self Assessment Program (MKSAP) 19 American College of Physicians, Philadelphia 2022
  22. ↑ 22.0 22.1 22.2 Tucker ME Eye check important before starting semaglutide for diabetes. Internal Medicine News. Jan 26, 2023 https://www.mdedge.com/internalmedicine/article/260856/diabetes/eye-check-important-starting-semaglutide-diabetes
    Albert SG, Wood ME, Ahir V Glucagon-like peptide 1-receptor agonists and A1c: Good for the heart but less so for the eyes? Diabetes Metab Syndr. 2022. Dec 28;17(1):102696 PMID: https://pubmed.ncbi.nlm.nih.gov/36596264 https://www.sciencedirect.com/science/article/abs/pii/S1871402122003137
  23. ↑ 23.0 23.1 NEJM Knowledge+ Endocrinology
  24. ↑ 24.0 24.1 Aroda VR et al. Efficacy and safety of once-daily oral semaglutide 25 mg and 50 mg compared with 14 mg in adults with type 2 diabetes (PIONEER PLUS): A multicentre, randomised, phase 3b trial. PMID: https://pubmed.ncbi.nlm.nih.gov/37385279 Lancet 2023 Jun 25; [e-pub]. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)01127-3/fulltext
    Knop FK et al. Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): A randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2023 Jun 25; [e-pub] PMID: https://pubmed.ncbi.nlm.nih.gov/37385278 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)01185-6/fulltext
  25. ↑ 25.0 25.1 25.2 Goodman B They took blockbuster drugs for weight loss and diabetes. Now their stomachs are paralyzed. CNN. July 25, 2023 https://www.cnn.com/2023/07/25/health/weight-loss-diabetes-drugs-gastroparesis/index.html
    Moniuszko M Ozempic, Mounjaro manufacturers sued over claims of "stomach paralysis" side effects. CBS News. August 3, 2023 https://www.cbsnews.com/news/ozempic-mounjaro-lawsuit-gastroparesis-stomach-paralysis-side-effect/
  26. ↑ 26.0 26.1 Zoler ML Wegovy Scores HFpEF Benefits in People With Obesity. Medscape. August 25, 2023 https://www.medscape.com/viewarticle/995844
    Kosiborod MN, Abildstrom SZ, Borlaug BA et al Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity. N Engl J Med. 2023. August 25. PMID: https://pubmed.ncbi.nlm.nih.gov/37622681 https://www.nejm.org/doi/full/10.1056/NEJMoa2306963
    Butler J, Abildstrom S, Borlaug B et al. Semaglutide in Patients With Obesity and Heart Failure Across Mildly Reduced or Preserved Ejection Fraction J Am Coll Cardiol. 2023. Nov 28;82(22):2087-2096. PMID: https://pubmed.ncbi.nlm.nih.gov/37993201 Free article https://www.jacc.org/doi/abs/10.1016/j.jacc.2023.09.811
    Borlaug BA, Kitzman DW, Davies MJ et al Semaglutide in HFpEF across obesity class and by body weight reduction: a prespecified analysis of the STEP-HFpEF trial. Nat Med. 2023 Sep;29(9):2358-2365. Epub 2023 Aug 27. PMID: https://pubmed.ncbi.nlm.nih.gov/37635157 PMCID: PMC10504076 Free PMC article.
  27. ↑ 27.0 27.1 27.2 Putka S FDA Adds Intestinal Blockage Reports to Ozempic Labeling. Joins other approved GLP-1 receptor agonists in noting the potential adverse reaction. MedPage Today September 28, 2023 https://www.medpagetoday.com/endocrinology/diabetes/106535
  28. ↑ 28.0 28.1 Lincoff AM et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med 2023 Nov 11; [e-pub]. PMID: https://pubmed.ncbi.nlm.nih.gov/37952131 https://www.nejm.org/doi/10.1056/NEJMoa2307563
  29. ↑ 29.0 29.1 Butler J, Abildstrom SZ, Borlaug BA et al. Semaglutide in Patients With Obesity and Heart Failure Across Mildly Reduced or Preserved Ejection Fraction. J Am Coll Cardiol. 2023 Nov 28;82(22):2087-2096. PMID: https://pubmed.ncbi.nlm.nih.gov/37993201 Free article https://www.sciencedirect.com/science/article/pii/S0735109723075964
  30. ↑ 30.0 30.1 Wang W et al. Association of semaglutide with risk of suicidal ideation in a real-world cohort. Nat Med 2024 Jan; 30:168 PMID: https://pubmed.ncbi.nlm.nih.gov/38182782 https://www.nature.com/articles/s41591-023-02672-2
  31. ↑ 31.0 31.1 Kosiborod MN, Verma S, Borlaug BA, et al. Effects of Semaglutide on Symptoms, Function, and Quality of Life in Patients With Heart Failure With Preserved Ejection Fraction and Obesity: A Prespecified Analysis of the STEP-HFpEF Trial. Circulation. 2024 Jan 16;149(3):204-216. PMID: https://pubmed.ncbi.nlm.nih.gov/37952180 PMCID: PMC10782938 Free PMC article https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.123.067505
  32. ↑ Yao H et al. Comparative effectiveness of GLP-1 receptor agonists on glycaemic control, body weight, and lipid profile for type 2 diabetes: Systematic review and network meta-analysis. BMJ 2024 Jan 29; 384:e076410. PMID: https://pubmed.ncbi.nlm.nih.gov/38286487 PMCID: PMC10823535 Free PMC article https://www.bmj.com/content/384/bmj-2023-076410
  33. ↑ 33.0 33.1 Hansen MK et al Eligibility for and Preventive Potential of Semaglutide in Overweight and Obese Patients With Myocardial Infarction. J Am Coll Cardiol. 2024 2024 Mar 5;83(9):956-958. PMID: https://pubmed.ncbi.nlm.nih.gov/38418010 https://www.jacc.org/doi/10.1016/j.jacc.2023.12.029
  34. ↑ 34.0 34.1 Monaco K Wegovy Approved for Major Heart Disease Prevention. New indication for patients with obesity or overweight and a history of cardiovascular disease. MedPage Today March 8, 2024 https://www.medpagetoday.com/cardiology/prevention/109090
  35. ↑ 35.0 35.1 Freiden J Medicare to Cover Weight-Loss Drug Wegovy for Certain Patients. News comes in the wake of FDA approval to reduce risk of heart attacks, stroke. MedPage Today March 21, 2024 https://www.medpagetoday.com/publichealthpolicy/medicare/109305
  36. ↑ 36.0 36.1 Kosiborod MN, Petrie MC, Borlaug BA et al. Semaglutide in patients with obesity-related heart failure and type 2 diabetes. N Engl J Med 2024 Apr 6; [e-pub]. PMID: https://pubmed.ncbi.nlm.nih.gov/38587233 https://www.nejm.org/doi/10.1056/NEJMoa2313917
  37. ↑ 37.0 37.1 Butler J, Shah SJ, Petrie MC et al Semaglutide versus placebo in people with obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomised trials. Lancet. 2024 Apr 4:S0140-6736(24)00469-0 PMID: https://pubmed.ncbi.nlm.nih.gov/38599221
  38. ↑ 38.0 38.1 Perkovic V et al Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes. N Engl J Med. 2024. May 23 PMID: https://pubmed.ncbi.nlm.nih.gov/38785209 https://www.nejm.org/doi/full/10.1056/NEJMoa2403347
  39. ↑ 39.0 39.1 Hathaway JT, Shah MP, Hathaway DB et al Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide. JAMA Ophthalmol. 2024 Jul 3. PMID: https://pubmed.ncbi.nlm.nih.gov/38958939 https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2820255
  40. ↑ 40.0 40.1 Schou M, Petrie MC, Borlaug BA, et al. Semaglutide and NYHA Functional Class in Obesity-Related Heart Failure With Preserved Ejection Fraction: The STEP-HFpEF Program. J Am Coll Cardiol. 2024 Jun 12:S0735-1097(24)07126-2. PMID: https://pubmed.ncbi.nlm.nih.gov/38913004 Free article
  41. ↑ 41.0 41.1 Rodriguez PJ, Goodwin Cartwright BM, Gratzl S et al Semaglutide vs Tirzepatide for Weight Loss in Adults With Overweight or Obesity. JAMA Intern Med. Published online July 8, 2024. PMID: https://pubmed.ncbi.nlm.nih.gov/38976257 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2821080
  42. ↑ 42.0 42.1 Lingvay I, Deanfield J, Kahn SE Semaglutide and Cardiovascular Outcomes by Baseline HbA1c and Change in HbA1c in People With Overweight or Obesity but Without Diabetes in SELECT. Diabetes Care. 2024 Jun 22:dc240764. PMID: https://pubmed.ncbi.nlm.nih.gov/38907684
  43. ↑ 43.0 43.1 Kahn SE, Deanfield JE, Jeppesen OK, et al. Effect of Semaglutide on Regression and Progression of Glycemia in People With Overweight or Obesity but Without Diabetes in the SELECT Trial. Diabetes Care. 2024 Jun 22:dc240491 PMID: https://pubmed.ncbi.nlm.nih.gov/38907683
  44. ↑ 44.0 44.1 44.2 Schoretsanitis G, Weiler S, Barbui C, Raschi E, Gastaldon C. Disproportionality Analysis From World Health Organization Data on Semaglutide, Liraglutide, and Suicidality. JAMA Netw Open. 2024 Aug 1;7(8):e2423385. PMID: https://pubmed.ncbi.nlm.nih.gov/39163046 PMCID: PMC11337067 Free PMC article.
  45. ↑ 45.0 45.1 Chaitoff A, Bendicksen L, Feldman WB, Zheutlin AR, Lalani HS Estimating new eligibility and maximum costs of expanded Medicare coverage of semaglutide for cardiovascular risk prevention. Ann Intern Med 2024 Aug 27 PMID: https://pubmed.ncbi.nlm.nih.gov/39186788 https://www.acpjournals.org/doi/10.7326/ANNALS-24-00308
  46. ↑ 46.0 46.1 Scirica BM, Lincoff AM, Lingvay I et al The Effect of Semaglutide on Mortality and COVID-19-Related Deaths: An Analysis From the SELECT Trial. J Am Coll Cardiol. 2024 Aug 27:S0735-1097(24)08156-7. PMID: https://pubmed.ncbi.nlm.nih.gov/39217559 Free article https://www.sciencedirect.com/science/article/pii/S0735109724081567
  47. ↑ 47.0 47.1 Deanfield J et al. Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: A prespecified analysis of the SELECT trial. Lancet 2024 Aug 24; 404:773-786 PMID: https://pubmed.ncbi.nlm.nih.gov/39181597 Free article. Clinical Trial. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)01498-3/fulltext
  48. ↑ 48.0 48.1 48.2 48.3 Henderson J The Data Are Clear: Patients Regain Weight After Stopping GLP-1 Drugs. Other than staying on drug, there's no evidence-based strategy to maintain weight loss. MedPage Today September 26, 2024 https://www.medpagetoday.com/special-reports/exclusives/112138
    Wilding JPH, Batterham RL, Davies M et al for the STEP 1 Study Group Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab. 2022 Aug;24(8):1553-1564. PMID: https://pubmed.ncbi.nlm.nih.gov/35441470 PMCID: PMC9542252 Free PMC article. Clinical Trial.
  49. ↑ 49.0 49.1 Wang W, Wang Q, Qi X et al Associations of semaglutide with first-time diagnosis of Alzheimer's disease in patients with type 2 diabetes: Target trial emulation using nationwide real-world data in the US. Alzheimers Dement. 2024 Oct 24. PMID: https://pubmed.ncbi.nlm.nih.gov/39445596
  50. ↑ 50.0 50.1 Dotinga R Wegovy Reduced Pain From Knee Osteoarthritis Patients taking the GLP-1 drug also had greater improvement in physical function. MedPage Today October 30, 2024 https://www.medpagetoday.com/rheumatology/arthritis/112646
    Watson T Anti-obesity drug has life-changing benefits for arthritis Clinical-trial participants saw their knee pain abate and could engage better with activities that got them up and going. Nature News. 2024. Oct 30. https://www.nature.com/articles/d41586-024-03512-0
    Bliddal H, Bays H, Czernichow S et al Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis. N Engl J Med. 2024 Oct 31;391(17):1573-1583. PMID: https://pubmed.ncbi.nlm.nih.gov/39476339 Clinical Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2403664
  51. ↑ 51.0 51.1 Mahaffey KW, Tuttle KR, Arici M et al Cardiovascular outcomes with semaglutide by severity of chronic kidney disease in type 2 diabetes: the FLOW trial. Eur Heart J. 2024 Aug 30:ehae613. PMID: https://pubmed.ncbi.nlm.nih.gov/39211948 https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehae613/7745056
  52. ↑ 52.0 52.1 Tucker ME Semaglutide 2.4 mg Reduces All-Cause Hospital Admissions. Medscape. Nov 4, 2024 https://www.medscape.com/viewarticle/semaglutide-2-4-mg-reduces-all-cause-hospital-admissions-2024a1000k3a
  53. ↑ Monaco K GLP-1 Drugs Could Help People With Alcohol Use Disorder. Real-world data suggested semaglutide, liraglutide reduced AUD-related hospitalizations. MedPage Today November 13, 2024 https://www.medpagetoday.com/psychiatry/addictions/112890
    Lahteenvuo M, Tiihonen J, Solismaa A Repurposing Semaglutide and Liraglutide for Alcohol Use Disorder. JAMA Psychiatry. 2024 Nov 13. PMID: https://pubmed.ncbi.nlm.nih.gov/39535805 https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2825650
  54. ↑ 54.0 54.1 Shi I, Khan SS, Yeh RW et al Semaglutide Eligibility Across All Current Indications for US Adults. JAMA Cardiol. 2024 Nov 18. PMID: https://pubmed.ncbi.nlm.nih.gov/39556764 https://jamanetwork.com/journals/jamacardiology/fullarticle/2826358
  55. ↑ 55.0 55.1 Hansen N Danish diabetes medicine increases the risk of severely debilitating eye condition. University of Southern Denmark. 2024. Dec 16 https://www.sdu.dk/en/om-sdu/fakulteterne/sundhedsvidenskab/nyheder/dansk-diabetesmedicin-oger-risikoen-for-svaert-invaliderende-ojensygdom
    Grauslund J, Taha AA, Molander LD et al Once-weekly semaglutide doubles the five-year risk of nonarteritic anterior ischemic optic neuropathy in a Danish cohort of 424,152 persons with type 2 diabetes. Int J Retina Vitreous. 2024 Dec 18;10(1):97. PMID: https://pubmed.ncbi.nlm.nih.gov/39696569 PMCID: PMC11657653 Free PMC article.
  56. ↑ Highights of Prescribing Information Ozempic (semaglutide) injection https://www.novo-pi.com/ozempic.pdf
  57. ↑ Highights of Prescribing Information Rybelsus (semaglutide) tablets for oral use https://www.novo-pi.com/rybelsus.pdf
  58. ↑ 58.0 58.1 Hendershot CS, Bremmer MO, Paladino MB et al Once-Weekly Semaglutide in Adults With Alcohol Use Disorder. A Randomized Clinical Trial. JAMA Psychiatry. Published online February 12, 2025 Not yet indexed in PubMed https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2829811
  59. ↑ 59.0 59.1 Monaco K Semaglutide Tied to Small Risk of Potentially Blinding Eye Condition Risk was smaller than previously reported, researchers say MedPage Today February 20, 2025 https://www.medpagetoday.com/ophthalmology/generalophthalmology/114293
    Cai CX, Hribar M, Baxter S et al Semaglutide and Nonarteritic Anterior Ischemic Optic Neuropathy. JAMA Ophthalmol. Published online February 20, 2025. PMID: https://pubmed.ncbi.nlm.nih.gov/39976940 PMCID: PMC11843465 Free PMC article. https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2830475
    Rizzo JF 3rd, Hathaway JT. Semaglutide and risk of NAION - Additional insights. JAMA Ophthalmol 2025 Feb 20; [e-pub]. PMID: https://pubmed.ncbi.nlm.nih.gov/39976950 https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2830477
  60. ↑ 60.0 60.1 Monaco K Wegovy Before Bariatric Surgery Not Tied to Greater Weight Loss. "The most effective weight-loss strategy isn't as simple as 1 + 1 = 2," says study author. MedPage Today March 5, 2025 https://www.medpagetoday.com/endocrinology/obesity/114516
  61. ↑ 61.0 61.1 Hwang JH, Laiteerapong N, Huang ES, Kim DD. Lifetime Health Effects and Cost-Effectiveness of Tirzepatide and Semaglutide in US Adults. JAMA Health Forum. 2025 Mar 7;6(3):e245586. PMID: https://pubmed.ncbi.nlm.nih.gov/40085108 PMCID: PMC11909610 Free PMC article. https://jamanetwork.com/journals/jama-health-forum/fullarticle/2831205
  62. ↑ 62.0 62.1 Lou N STRIDE: Semaglutide Shows it Has Legs in Peripheral Artery Disease. Plus, oral version of GLP-1 drug boasts cardiovascular efficacy in SOUL. MedPage Today March 29, 2025 https://www.medpagetoday.com/meetingcoverage/acc/114883
    Bonaca MP, Catarig AM, Houlind K et al for the STRIDE Trial Investigators. Semaglutide and walking capacity in people with symptomatic peripheral artery disease and type 2 diabetes (STRIDE): a phase 3b, double-blind, randomised, placebo-controlled trial. Lancet. 2025 Mar 28:S0140-6736(25)00509-4. PMID: https://pubmed.ncbi.nlm.nih.gov/40169145
  63. ↑ 63.0 63.1 McGuire DK et al. Oral semaglutide and cardiovascular outcomes in high-risk type 2 diabetes. N Engl J Med 2025 Mar 29; [e-pub] PMID: https://pubmed.ncbi.nlm.nih.gov/40162642 https://www.nejm.org/doi/10.1056/NEJMoa2501006
  64. ↑ 64.0 64.1 No authors listed Phase 3 ESSENCE Trial: Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis. Gastroenterol Hepatol (N Y). 2024. PMID: https://pubmed.ncbi.nlm.nih.gov/39896971 PMCID: PMC11784563 Free PMC article.
    Sanyal AJ, et al. Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis. N Engl J Med. 2025. PMID: https://pubmed.ncbi.nlm.nih.gov/40305708 https://www.nejm.org/doi/10.1056/NEJMoa2413258
  65. ↑ 65.0 65.1 Lovegrove MC, Stone ND, Geller AI, Weidle NJ, Lind JN, Cohen PA. U.S. Emergency Department Visits Attributed by Clinicians to Semaglutide Adverse Events, 2022-2023. Ann Intern Med. 2025 Apr 8. PMID: https://pubmed.ncbi.nlm.nih.gov/40194288 No abstract available. https://www.acpjournals.org/doi/10.7326/ANNALS-24-03258
  66. ↑ 66.0 66.1 Chen JC, Huang YN, Tsou MY et al Comparative analysis of GLP-1 receptor agonists, traditional glucose-lowering medications and traditional anti-obesity medications on skeletal outcomes in obese individuals with and without type 2 diabetes: a five-year propensity- score matched cohort study. Endocrine Abstracts (2025) 110 P684 Not yet indexed in Pubmed https://www.endocrine-abstracts.org/ea/0110/ea0110p684
  67. ↑ 67.0 67.1 67.2 Dotinga R Semaglutide Linked to Age-Related Macular Degeneration Risk. Another ocular condition tied to GLP-1 drugs when taken by patients with diabetes. MedPage Today June 5, 2025 https://www.medpagetoday.com/ophthalmology/generalophthalmology/115919
    Shor R, Mihalache A, Noori A et al Glucagon-Like Peptide-1 Receptor Agonists and Risk of Neovascular Age-Related Macular Degeneration. JAMA Ophthalmol. 2025 Jun 5. PMID: https://pubmed.ncbi.nlm.nih.gov/40471562 https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2834964
  68. ↑ 68.0 68.1 Rossing P, Bakris G, Perkovic V for the FLOW Investigator Group Effects of Semaglutide With or Without Concomitant Mineralocorticoid Receptor Antagonist Use in Participants With Type 2 Diabetes and Chronic Kidney Disease: A FLOW Trial Prespecified Secondary Analysis. Diabetes Care. 2025 Jul 29:dc250472. . PMID: https://pubmed.ncbi.nlm.nih.gov/40730031
  69. ↑ Wharton S et al Once-weekly semaglutide 72 mg in adults with obesity (STEP UP): a randomised, controlled, phase 3b trial. Lancet Diabetes & Endocrinology. 2025. Sept 14 Not yet indexed in PubMed https://www.thelancet.com/journals/landia/article/PIIS2213-8587(25)00226-8/abstract
    Lingvay I et al Once-weekly semaglutide 72 mg in adults with obesity and type 2 diabetes (STEP UP T2D): a randomised, controlled, phase 3b trial. Lancet Diabetes & Endocrinology. 2025. Sept 14 Not yet indexed in PubMed https://www.thelancet.com/journals/landia/article/PIIS2213-8587(25)00225-6/abstract
  70. ↑ Sanyal AJ et al. Phase 3 trial of semaglutide in metabolic dysfunction-associated steatohepatitis. N Engl J Med 2025 Jun 5; 392:2089 PMID: https://pubmed.ncbi.nlm.nih.gov/40305708 https://www.nejm.org/doi/10.1056/NEJMoa2413258
  71. ↑ 71.0 71.1 Wharton S, Lingvay I, Bogdanski P, et al. Oral Semaglutide at a Dose of 25 mg in Adults with Overweight or Obesity. N Engl J Med. 2025 Sep 18;393(11):1077-1087 https://www.nejm.org/doi/10.1056/NEJMoa2500969
  72. ↑ Medscape: semaglutide (Rx) https://reference.medscape.com/drug/ozempic-rybelsus-wegovy-semaglutide-1000174
  73. ↑ U.S. Food and Drug Administration. WEGOVY (semaglutide) injection, for subcutaneous use: Official prescribing information. Aug 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215256s024lbl.pdf
  74. ↑ 74.0 74.1 74.2 Lingvay I, Bergenheim SJ, Buse JB, et al. Once-weekly semaglutide 7.2 mg in adults with obesity and type 2 diabetes (STEP UP T2D): a randomised, controlled, phase 3b trial. Lancet Diabetes Endocrinol. 2025 Sep 14:S2213-8587(25)00225-6. PMID: https://pubmed.ncbi.nlm.nih.gov/40961953
    Wharton S, Freitas P, Hjelmesaeth J, et al. Once-weekly semaglutide 7.2 mg in adults with obesity (STEP UP): a randomised, controlled, phase 3b trial. Lancet Diabetes Endocrinol. 2025 Sep 14:S2213-8587(25)00226-8. PMID: https://pubmed.ncbi.nlm.nih.gov/40961952
  75. ↑ 75.0 75.1 Deanfield J et al Semaglutide and cardiovascular outcomes by baseline and changes in adiposity measurements: a prespecified analysis of the SELECT trial. Lancet 2025 Oct 25 Not yet indexed in PubMed https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)01375-3/fulltext
  76. ↑ Guo H, Guo Q, Li Z, Wang Z. Association between different GLP-1 receptor agonists and acute pancreatitis: case series and real-world pharmacovigilance analysis. Front Pharmacol. 2024 Nov 13;15:1461398. PMID: https://pubmed.ncbi.nlm.nih.gov/39605914 PMCID: PMC11600108 Free PMC article. https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1461398/full

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