Body Composition Changes with Semaglutide: A Systematic Review and Meta-Analysis

Introduction: Semaglutide is effective for weight loss, but the relative contributions of fat and fat-free mass (FFM) to total weight loss remain unclear. Methods: This was a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating semaglutide in adults with overweight or obesity. Searches were performed in PubMed, Web of Science, Embase, and Scopus through April 2025. Eligible trials reported baseline and post-treatment measures of body mass, fat mass, and FFM. Data extraction followed PRISMA guidelines, and risk of bias and certainty of evidence were assessed. Random-effects models were applied, with linear or quadratic functions fitted as appropriate. Results: Seven RCTs involving 452 participants (259 semaglutide, 193 placebo) met the inclusion criteria. Semaglutide produced significant non-linear weight loss (0.04 kg/day; 95% CI 0.03-0.05; p<0.0001), primarily due to fat mass reduction (0.03 kg/day; 95% CI 0.01-0.05; p=0.007). FFM declined linearly at a smaller rate (0.007 kg/day; 95% CI 0.003-0.010; p=0.0001). Certainty of evidence was moderate. Conclusion: Semaglutide induces substantial reductions in body and fat mass, with modest FFM loss. Clinical strategies combining semaglutide with resistance exercise and nutritional support may help preserve lean mass and optimize long-term outcomes.