Comparative Effects of Antidiabetic Drugs on Body Composition: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Antidiabetic drugs differ in their effects on body composition, which may influence metabolic and functional outcomes. This systematic review and network meta-analysis aimed to quantify and compare effects of major antidiabetic drugs on key body composition parameters. METHODS: PubMed, Web of Science and Scopus were searched from inception to March 2025 for randomized controlled trials. Network meta-analyses used a frequentist random-effects framework to estimate mean differences (MDs) and 95% confidence intervals (CIs) for changes in fat mass (FM) and lean body mass (LBM). RESULTS: Forty-one trials involving 2906 participants were included. For FM among Glucagon-like peptide-1 (GLP-1) and dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists, tirzepatide showed the greatest reduction compared with placebo (MD -10.70 kg; 95% CI: -13.42 to -7.99), followed by liraglutide plus exercise. Semaglutide and liraglutide produced moderate reductions. In contrast, insulin glargine and alogliptin were associated with FM gain relative to metformin and exenatide. For LBM, tirzepatide (MD -4.40 kg; 95% CI: -7.58 to -1.22) and liraglutide (MD -1.54 kg; 95% CI: -2.55 to -0.52) were associated with significant reductions. Sodium-glucose cotransporter-2 (SGL2) inhibitors caused minor losses, whereas metformin, insulin regimens and dipeptidyl peptidase-4 (DPP4) inhibitors showed neutral effects. CONCLUSION: GLP-1 and dual GIP/GLP-1 receptor agonists produced the greatest FM reduction but also decreased lean mass. Exercise mitigated liraglutide-related LBM loss. SGLT2 inhibitors showed modest effects, while metformin, insulin, DPP4 inhibitors and sulfonylureas had minimal impact. Further research on dose, duration and lifestyle influences is warranted.