Obesity places patients at higher risk for numerous problems, including prediabetes, type 2 diabetes mellitus (T2DM), hypertension, metabolic syndrome, cardiovascular disease, and nonalcoholic fatty liver disease. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are antidiabetic drugs that have a recognized effect on weight loss. This systematic review analyzed semaglutide against alternative GLP-1 agonists in facilitating weight loss and evaluated their associated adverse events (AEs) in diabetic patients. A systematic search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was performed using PubMed, Embase, and Cochrane Library for studies comparing semaglutide and other GLP-1 RAs for weight loss. A narrative synthesis and meta-analysis using SPSS program version 29 were performed to analyze the differences in weight loss between cohorts. Nine studies with 5,445 patients whose mean age was 60.01 years (55.5-70) and mean follow-up of 32.5 weeks (4-58.7) were included. The meta-analysis showed that semaglutide had a greater mean weight loss compared to liraglutide (-6.08, 95% confidence interval (Cl) = -8.40, -3.75) and dulaglutide (-2.85, 95% CI = -5.59, 0.11). Tirzepatide had a greater mean weight loss compared to semaglutide (-3.78, 95% CI = -5.52, -2.04). Common AEs included minor and moderate gastrointestinal events. In conclusion, GLP-1 RAs have shown efficacy in reducing body weight in T2DM patients. Semaglutide, liraglutide, dulaglutide, tirzepatide, and exenatide demonstrated mean weight loss reductions of 4.81 kg, 2.81 kg, 4.03 kg, 9.7 kg, and 1.9 kg, respectively, with high rates of minimal to moderate-severity AEs. Semaglutide demonstrated increased numerical weight loss compared to its comparators (dulaglutide, liraglutide, and exenatide). However, tirzepatide, a dual-agonist, produced greater weight loss compared to semaglutide. The paucity of comparative head-to-head trials prevents a definitive conclusion of the superiority of one GLP-1 RA over another.
