Comparison of the Effectiveness and Safety of GLP-1 Receptor Agonists in Type 2 Diabetes Mellitus Patients with Overweight or Obesity
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Background: Glucagon-like peptide-1 receptor agonists improve glycemic control and support body weight reduction in patients with type 2 diabetes mellitus, but local comparative evidence between semaglutide and liraglutide in patients with overweight or obesity remains limited. Objective: To compare the 24-week effectiveness and short-term safety of once-weekly semaglutide versus once-daily liraglutide among adults with type 2 diabetes mellitus and overweight or obesity. Methods: This prospective, non-randomized, two-arm comparative study was conducted at Nishtar Hospital, Multan, Pakistan, from January 2025 to December 2025. Ninety-two adults with type 2 diabetes mellitus, HbA1c 7.0–10.0%, and body mass index ≥25 kg/m² were assigned by systematic alternate allocation to semaglutide (n=46) or liraglutide (n=46), alongside lifestyle counseling and background antidiabetic care. Outcomes were assessed at 24 weeks. Results: Semaglutide was associated with greater HbA1c reduction than liraglutide (-1.55 ± 0.62% vs -1.08 ± 0.59%; mean difference -0.47%, 95% CI -0.72 to -0.22; p<0.001) and greater body weight reduction (-5.8 ± 3.1 kg vs -3.2 ± 2.6 kg; mean difference -2.60 kg, 95% CI -3.79 to -1.41; p<0.001). At least 5% body weight reduction was achieved by 58.7% versus 32.6% of participants, respectively (p=0.012). Gastrointestinal symptoms were the most frequent adverse events and were comparable between groups. No severe hypoglycemia, confirmed pancreatitis, or acute gallbladder event was observed. Conclusion: Semaglutide was associated with greater glycemic and weight reduction than liraglutide over 24 weeks, with broadly comparable short-term tolerability. Treatment selection should consider efficacy, safety, cost, availability, renal status, adherence likelihood, and patient preference
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1. Davies MJ, Aroda VR, Collins BS, Gabbay RA, Green J, Maruthur NM, et al. Management of hyperglycemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2022;45(11):2753-86. doi:10.2337/dci22-0034.
2. Nauck MA, Quast DR, Wefers J, Meier JJ. GLP-1 receptor agonists in the treatment of type 2 diabetes: state-of-the-art. Mol Metab. 2021;46:101102. doi:10.1016/j.molmet.2020.101102.
3. Drucker DJ. Mechanisms of action and therapeutic application of glucagon-like peptide-1. Cell Metab. 2018;27(4):740-56. doi:10.1016/j.cmet.2018.03.001.
4. Capehorn MS, Catarig AM, Furberg JK, Janez A, Price HC, Tadayon S, et al. Efficacy and safety of once-weekly semaglutide 1.0 mg versus once-daily liraglutide 1.2 mg as add-on to 1-3 oral antidiabetic drugs in subjects with type 2 diabetes: SUSTAIN 10. Diabetes Metab. 2020;46(2):100-9. doi:10.1016/j.diabet.2019.101117.
5. Pratley RE, Aroda VR, Lingvay I, Ludemann J, Andreassen C, Navarria A, et al. Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes: SUSTAIN 7. Lancet Diabetes Endocrinol. 2018;6(4):275-86. doi:10.1016/S2213-8587(18)30024-X.
6. Dungan KM, Povedano ST, Forst T, Gonzalez JG, Atisso C, Sealls W, et al. Once-weekly dulaglutide versus once-daily liraglutide in metformin-treated patients with type 2 diabetes: AWARD-6. Lancet. 2014;384(9951):1349-57. doi:10.1016/S0140-6736(14)60976-4.
7. Buse JB, Nauck M, Forst T, Sheu WHH, Shenouda SK, Heilmann CR, et al. Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes: DURATION-6. Lancet. 2013;381(9861):117-24. doi:10.1016/S0140-6736(12)61267-7.
8. Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JFE, Nauck MA, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375(4):311-22. doi:10.1056/NEJMoa1603827.
9. Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jodar E, Leiter LA, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375(19):1834-44. doi:10.1056/NEJMoa1607141.
10. Davies M, Faerch L, Jeppesen OK, Pakseresht A, Pedersen SD, Perreault L, et al. Semaglutide 2.4 mg once a week in adults with overweight or obesity, and type 2 diabetes: STEP 2. Lancet. 2021;397(10278):971-84. doi:10.1016/S0140-6736(21)00213-0.
11. Sorli C, Harashima SI, Tsoukas GM, Unger J, Karsbol JD, Hansen T, et al. Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes: SUSTAIN 1. Lancet Diabetes Endocrinol. 2017;5(4):251-60. doi:10.1016/S2213-8587(17)30013-X.
12. Ahren B, Masmiquel L, Kumar H, Sargin M, Karsbol JD, Jacobsen SH, et al. Efficacy and safety of once-weekly semaglutide versus once-daily sitagliptin as an add-on to metformin, thiazolidinediones, or both, in patients with type 2 diabetes: SUSTAIN 2. Lancet Diabetes Endocrinol. 2017;5(5):341-54. doi:10.1016/S2213-8587(17)30092-X.
13. Aroda VR, Bain SC, Cariou B, Piletič M, Rose L, Axelsen M, et al. Efficacy and safety of once-weekly semaglutide versus once-daily insulin glargine as add-on to metformin, with or without sulfonylureas, in insulin-naive patients with type 2 diabetes: SUSTAIN 4. Lancet Diabetes Endocrinol. 2017;5(5):355-66. doi:10.1016/S2213-8587(17)30085-2.
14. Frias JP, Auerbach P, Bajaj HS, Fukushima Y, Hansen MR, Liu B, et al. Efficacy and safety of once-weekly semaglutide 2.0 mg versus 1.0 mg in patients with type 2 diabetes: SUSTAIN FORTE. Lancet Diabetes Endocrinol. 2021;9(9):563-74. doi:10.1016/S2213-8587(21)00174-1.
15. Zinman B, Bhosekar V, Busch R, Holst I, Ludvik B, Thielke D, et al. Semaglutide once weekly as add-on to SGLT-2 inhibitor therapy in type 2 diabetes: SUSTAIN 9. Lancet Diabetes Endocrinol. 2019;7(5):356-67. doi:10.1016/S2213-8587(19)30066-X.
16. Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384(11):989-1002. doi:10.1056/NEJMoa2032183.
17. Garvey WT, Batterham RL, Bhatta M, Buscemi S, Christensen LN, Frias JP, et al. Two-year effects of semaglutide in adults with overweight or obesity: STEP 5. Nat Med. 2022;28(10):2083-91. doi:10.1038/s41591-022-02025-4.
18. Husain M, Birkenfeld AL, Donsmark M, Dungan K, Eliaschewitz FG, Franco DR, et al. Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2019;381(9):841-51. doi:10.1056/NEJMoa1901118.
19. Kristensen SL, Rorth R, Jhund PS, Docherty KF, Sattar N, Preiss D, et al. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet Diabetes Endocrinol. 2019;7(10):776-85. doi:10.1016/S2213-8587(19)30249-9.
20. Sattar N, Lee MMY, Kristensen SL, Branch KRH, Del Prato S, Khurmi NS, et al. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of randomised trials. Lancet Diabetes Endocrinol. 2021;9(10):653-62. doi:10.1016/S2213-8587(21)00203-5.