Background/Objectives: Excess adipose tissue is associated with adverse changes in muscle metabolism and body composition. GLP-1 receptor agonists (GLP-1 RA) have transformed the treatment of obesity; however, concerns remain regarding the potential impact of treatment-associated weight loss on lean mass. This study aimed to evaluate the effects of GLP-1 RA on body composition in adults with obesity without type II diabetes mellitus (T2DM), with a particular focus on changes in lean mass. Methods: A database search of Medline Ultimate, Scopus, Web of Science, PubMed, and Embase was conducted to identify studies published up to December 30, 2024. Randomized controlled trials involving adults with obesity and without T2DM who received GLP-1 RA and reported changes in body composition were included. The protocol was registered with PROSPERO (CRD42025645378). Random-effects meta-analysis was performed using inverse-variance weighting. Results: A total of 2776 articles were identified, of which three trials comprising 171 participants met the inclusion criteria. Compared with controls, participants receiving GLP-1 RA treatment experienced greater reductions in lean mass (MD = -0.78 kg, 95% CI: [-1.37 to -0.16], I2 = 63.2%). GLP-1 RA treatment was also associated with a significant reduction in fat mass (MD = -3.43 kg, 95% CI: [-5.94 to -0.93], I2 = 78.2%). Conclusions: The loss of lean mass was greater in patients treated with GLP-1 RA than in the control group. These results highlight the importance for clinicians to incorporate lifestyle interventions, including physical activity and nutritional support, alongside therapy with GLP-1 RA.
