GLP-1 agonists and changes in body mass and composition in adults with overweight or obesity with or without type 2 diabetes mellitus: a systematic review and meta-analysis

BACKGROUND: The systematic review aimed to assess the effects of GLP-1 receptor agonists (GLP-1 RA) and dual GLP-1/GIP agonists on weight loss and body composition in individuals with overweight or obesity, with or without type 2 diabetes mellitus. METHODS: The study protocol was registered in PROSPERO (CRD420251002447). A systematic search of PubMed, Scopus, and Web of Science was conducted up to December 2024 according to PRISMA guidelines. Following the predefined inclusion and exclusion criteria, 36 studies were included in this systematic review and underwent qualitative analysis. In addition, 24 studies met the criteria for quantitative synthesis (meta-analysis). Data were pooled using random-effects models with subgroup analyses by drug type and treatment duration (3, 6, and 12 months). RESULTS: GLP-1 RA treatment consistently reduced body weight, BMI, and waist circumference across all time points. At 3 months, mean body weight decreased by approximately 9%, accompanied by marked reductions in fat mass and visceral adipose tissue. At 6 months, weight reduction averaged 5%, with semaglutide, liraglutide, and exenatide showing comparable effects, while lean mass remained largely preserved. At 12 months, weight loss persisted at around 4%, with variability between agents, most notably liraglutide. Across studies, fat mass decline predominated, whereas reductions in lean body mass were modest. CONCLUSION: GLP-1 RAs provide clinically meaningful weight loss primarily through selective fat mass reduction, with relative preservation of lean tissue, supporting their role in achieving "quality" weight loss. Differences between agents highlight the importance of individualized treatment strategies, complemented by nutritional and exercise interventions to optimize long-term outcomes.