AIM: To compare the effects of individual glucagon-like peptide-1 receptor agonists (GLP-1RAs) on direct body composition among adults with overweight or obesity, with or without type 2 diabetes (T2D).
METHODS: We systematically searched six electronic databases and grey literature from inception to 3 November 2025, to identify all randomised controlled trials (RCTs) that investigated individual GLP-1RAs on change in body composition from baseline among adults with overweight or obesity with or without T2D, without language restrictions. The main outcomes included total body fat (%), fat mass (kg), visceral adipose tissue (VAT) area (cm), subcutaneous adipose tissue (SAT) area (cm), liver fat content (%), total lean tissue (%) and lean mass (kg). A frequentist network meta-analysis was employed using a random-effects model and reported as standardised mean differences (SMDs). Certainty of evidence was appraised using the Confidence in Network Meta-Analysis. 2 2
RESULTS: We identified 43 unique RCTs with 3379 participants that compared 17 different interventions or dosages with a control group. Regarding variations in treatment benefits on body composition, GLP-1RAs subcutaneously were more efficacious than the control group in decreasing total body fat, fat mass, VAT, SAT and liver fat from baseline. No significant differences for change in total lean tissue were observed. However, subcutaneously, liraglutide 1.8 mg/day, semaglutide 1.0 mg-weekly and tirzepatide 15 mg-weekly (SMDs ranged from -1.09 to -0.50) significantly decreased lean mass from baseline.
CONCLUSIONS: GLP-1RAs substantially improve body composition-related excess adiposity, but unfavourable effects on lean mass were observed, particularly at high doses.
GLP-1 Therapies