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Review of Efficacy and Safety of Semaglutide in the Management of Obesity

비만 치료에서 semaglutide의 효능 및 안전성에 대한 고찰

  • Received : 2024.01.23
  • Accepted : 2024.03.05
  • Published : 2024.03.31

Abstract

This review examines the pivotal clinical trials that evaluated the efficacy and safety of semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, in the management of obesity. The reported findings underscore significant and sustained weight loss achieved with semaglutide in diverse patient groups, although gastrointestinal disorders occurred frequently, leading to therapy discontinuation. Overall, the studies demonstrated the potential of semaglutide as a therapeutic option not only for type 2 diabetes but also for obesity. The treatment landscape in obesity is evolving, as reflected in changing regulatory approvals and clinical guidelines, suggesting a paradigm shift toward personalized approaches in this chronic disease states to achieve optimal treatment outcomes for patients.

Keywords

References

  1. Korean Society for the Study of Obesity. Clinical practice guidelines for obesity, 8th edition. 2022:1-17.
  2. Korean Society for the Study of Obesity. 2021 obesity fact sheet. Available from https://www.kosso.or.kr/file/2021_Obesity_Fact_Sheet_web_kor.pdf?v=2307210355. Accessed July 21, 2023.
  3. Korean Diabetes Association. Clinical practice guidelines for diabetes. 2023:21-183.
  4. Drucker DJ, Nauck MA. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet. 2006;368(9548):1696-705. https://doi.org/10.1016/S0140-6736(06)69705-5
  5. Holst JJ. Glucagonlike peptide 1: a newly discovered gastrointestinal hormone. Gastroenterology 1994;107(6):1848-55. https://doi.org/10.1016/0016-5085(94)90831-1
  6. Vilsboll T, Krarup T, Deacon CF, Madsbad S, Holst JJ. Reduced postprandial concentrations of intact biologically active glucagon-like peptide 1 in type 2 diabetic patients. Diabetes 2001;50(3):609-13. https://doi.org/10.2337/diabetes.50.3.609
  7. Clarke T. FDA approves Novo Nordisk diabetes drug Ozempic. Reuters. 2017. Available from https://www.reuters.com/article/idUSKBN1DZ2O8/. Accessed December 18, 2023.
  8. U.S. Food and Drug Administration. FDA approves new drug treatment for chronic weight management, first since 2014. 2021. Available from https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-treatment-chronic-weight-managementfirst-2014. Accessed December 18, 2023.
  9. Ministry of Food and Drug Safety. Ozempic prefilled pen (semaglutide). Available from https://nedrug.mfds.go.kr/pbp/CCBBB01/getItemDetailCache?cacheSeq=202201737aupdateTs2023-07-03%2017:55:00.0b. Accessed December 18, 2023.
  10. Ministry of Food and Drug Safety. Wegovy prefilled pen (semaglutide). Available from https://nedrug.mfds.go.kr/pbp/CCBBB01/getItemDetailCache?cacheSeq=202301387aupdateTs2023-12-15%2013:45:40.397763b. Accessed December 18, 2023.
  11. U.S. Food and Drug Administration. FDA approves first oral GLP-1 treatment for type 2 diabetes. 2019. Available from https://www.fda.gov/news-events/press-announcements/fda-approves-first-oral-glp-1-treatment-type-2-diabetes. Accessed December 18, 2023.
  12. Ministry of Food and Drug Safety. Rybelsus (semaglutide). Available from https://nedrug.mfds.go.kr/pbp/CCBBB01/getItemDetailCache?cacheSeq=202201785aupdateTs2023-11-09%2011:24:14.969223b. Accessed December 18, 2023.
  13. Sorli C, 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 Endocrinol 2017;5(4):251-60. https://doi.org/10.1016/S2213-8587(17)30013-X
  14. Rodbard HW, Lingvay I, Reed J, et al. Semaglutide Added to Basal Insulin in Type 2 Diabetes (SUSTAIN 5): A Randomized, Controlled Trial. J Clin Endocrinol Metab 2018;103(6):2291-301. https://doi.org/10.1210/jc.2018-00070
  15. Zinman B, Bhosekar V, Busch R, et al. Semaglutide once weekly as add-on to SGLT-2 inhibitor therapy in type 2 diabetes (SUSTAIN 9): a randomised, placebo-controlled trial. Lancet Diabetes Endocrinol 2019;7(5):356-67. https://doi.org/10.1016/S2213-8587(19)30066-X
  16. Ahmann AJ, Capehorn M, Charpentier G, et al. Efficacy and safety of once-weekly semaglutide versus exenatide ER in subjects with type 2 diabetes (SUSTAIN 3): A 56-week, open-label, randomized clinical trial. Diabetes Care 2018;41(2):258-66. https://doi.org/10.2337/dc17-0417
  17. 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 Endocrinol 2018;6(4):275-86. https://doi.org/10.1016/S2213-8587(18)30024-X
  18. Capehorn MS, Catarig AM, Furberg JK, et al. Efficacy and safety of once-weekly semaglutide 1.0mg vs once-daily liraglutide 1.2mg as add-on to 1-3 oral antidiabetic drugs in subjects with type 2 diabetes (SUSTAIN 10). Diabetes Metab 2020;46(2):100-9. https://doi.org/10.1016/j.diabet.2019.101117
  19. 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 Endocrinol 2019;7(11):834-44. https://doi.org/10.1016/S2213-8587(19)30311-0
  20. Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med 2021;384(11):989-1002. https://doi.org/10.1056/NEJMoa2032183
  21. 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 2021;325(14):1414-25. https://doi.org/10.1001/jama.2021.3224
  22. 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;325(14):1403-13. https://doi.org/10.1001/jama.2021.1831
  23. Garvey WT, Batterham RL, Bhatta M, et al. Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. Nat Med 2022;28(10):2083-91. https://doi.org/10.1038/s41591-022-02026-4
  24. Weghuber D, Barrett T, Barrientos-Perez M, et al. Once-weekly semaglutide in adolescents with obesity. N Engl J Med 2022;387(24):2245-57. https://doi.org/10.1056/NEJMoa2208601
  25. Rubino DM, Greenway FL, Khalid U, et al. Effect of weekly subcutaneous semaglutide vs daily liraglutide on body weight in adults with overweight or obesity without diabetes: The STEP 8 randomized clinical trial. JAMA 2022;327(2):138-50. https://doi.org/10.1001/jama.2021.23619
  26. Frias JP, Davies MJ, Rosenstock J, et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med 2021;385(6):503-15. https://doi.org/10.1056/NEJMoa2107519
  27. McGowan BM, Houshmand-Oeregaard A, Laursen PN, Zeuthen N, Baker-Knight J. Impact of BMI and comorbidities on efficacy of once-weekly semaglutide: Post hoc analyses of the STEP 1 randomized trial. Obesity (Silver Spring) 2023;31(4):990-28.
  28. Wilding JPH, Batterham RL, Davies M, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab 2022;24(8):1553-64. https://doi.org/10.1111/dom.14725
  29. Aroda VR, Rosenstock J, Terauchi Y, et al. PIONEER 1: Randomized clinical trial of the efficacy and safety of oral semaglutide monotherapy in comparison with placebo in patients with type 2 diabetes. Diabetes Care 2019;42(9):1724-32. https://doi.org/10.2337/dc19-0749
  30. Mosenzon O, Blicher TM, Rosenlund S, et al. Efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment (PIONEER 5): a placebo-controlled, randomised, phase 3a trial. Lancet Diabetes Endocrinol 2019;7(7):515-27. https://doi.org/10.1016/S2213-8587(19)30192-5
  31. 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;394(10192):39-50. https://doi.org/10.1016/S0140-6736(19)31271-1
  32. Rodbard HW, Rosenstock J, Canani LH, et al. Oral semaglutide versus empagliflozin in patients with type 2 diabetes uncontrolled on metformin: The PIONEER 2 trial. Diabetes Care 2019;42(12):2272-81. https://doi.org/10.2337/dc19-0883
  33. Yabe D, Nakamura J, Kaneto H, et al. Safety and efficacy of oral semaglutide versus dulaglutide in Japanese patients with type 2 diabetes (PIONEER 10): an open-label, randomised, active-controlled, phase 3a trial. Lancet Diabetes Endocrinol 2020;8(5):392-406. https://doi.org/10.1016/S2213-8587(20)30074-7
  34. Yamada Y, Katagiri H, Hamamoto Y, et al. Dose-response, efficacy, and safety of oral semaglutide monotherapy in Japanese patients with type 2 diabetes (PIONEER 9): a 52-week, phase 2/3a, randomised, controlled trial. Lancet Diabetes Endocrinol 2020;8(5):377-91. https://doi.org/10.1016/S2213-8587(20)30075-9
  35. Zinman B, Aroda VR, Buse JB, et al. Efficacy, safety, and tolerability of oral semaglutide versus placebo added to insulin with or without metformin in patients with type 2 diabetes: The PIONEER 8 trial. Diabetes Care 2019;42(12):2262-71. https://doi.org/10.2337/dc19-0898
  36. Knop FK, Aroda VR, do Vale RD, 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;402(10403):705-19.
  37. American Diabetes Association. Standards of care in diabetes - 2023. Diabetes Care 2023;46(Suppl. 1).
  38. Blonde L, Umpierrez GE, Reddy SS, et al. American Association of Clinical Endocrinology clinical practice guideline: developing a diabetes mellitus comprehensive care plan - 2022 update. Endocr Pract 2022;28(10):923-1049.
  39. Korean Diabetes Association. Clinical practice guidelines for diabetes, 7th edition. 2021:89.
  40. Korean Diabetes Association. Clinical practice guidelines for diabetes, 8th edition. 2023:125.
  41. Grunvald E, Shah R, Hernaez R, et al. AGA clinical practice guideline on pharmacological interventions for adults with obesity. Gastroenterology 2022;163(5):1198-225. https://doi.org/10.1053/j.gastro.2022.08.045
  42. DrFirst. Ozempic this, Wegovy that: no matter what you call it, semaglutide is having a moment. 2023. Available from https://drfirst.com/press-releases/ozempic-this-wegovy-that-no-matter-what-youcall-it-semaglutide-is-having-a-moment/. Accessed February 13, 2024.
  43. McPhillips D. CNN exclusive: prescriptions for popular diabetes and weight-loss drugs soared, but access is limited for some patients. CNN. 2023. Available from https://edition.cnn.com/2023/09/27/health/semaglutide-equitable-access/index.html. Accessed February 13, 2024.
  44. American Society of Health-System Pharmacists. Semaglutide injection. 2024. Available from https://www.ashp.org/drug-shortages/current-shortages/drug-shortage-detail.aspx?id=813&loginreturnUrl=SSOCheckOnly. Accessed February 13, 2024.
  45. Klein HE. An ongoing crisis: semaglutide shortage raises dual concerns for obesity and diabetes treatment. American Journal of Managed Care. 2023. Available from https://www.ajmc.com/view/an-ongoing-crisis-semaglutide-shortage-raises-dual-concerns-for-obesity-and-diabetes-treatment. Accessed February 13, 2024.
  46. Leitner DR, Fruhbeck G, Yumuk V, et al. Obesity and type 2 diabetes: two diseases with a need for combined treatment strategies - EASO can lead the way. Obes Facts 2017;10(5):483-92. https://doi.org/10.1159/000480525
  47. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med 2023;389(24):2221-32. https://doi.org/10.1056/NEJMoa2307563
  48. Wegovy (semaglutide) [Package Insert] Novo Nordis; Bagsvaerd, Denmark: 2022.
  49. Park ET. Finally, a survey?...Is misuse of 'obesity treatment' okay? Medipana. 2023. Available from: https://www.medipana.com/article/view.php?news_idx=317626. Accessed February 29, 2024.