Abstract
BACKGROUND: Obesity is a complex condition marked by excessive body fat, linked to comorbidities such as type 2 diabetes and cardiovascular disease. Glucagon-like peptide-1 (GLP-1) receptor agonists, initially developed for diabetes, are increasingly used for weight management. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (PubMed, last 5 years, English language) evaluating GLP-1-based pharmacotherapies versus placebo or active comparators for weight loss. The primary endpoint was the proportion of participants achieving any weight loss during follow-up. Pooled odds ratios were estimated using a fixed-effect model with 95% confidence intervals; heterogeneity was quantified with I2. A frequentist network meta-analysis generated SUCRA rankings. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. No protocol was registered. RESULTS: Twenty-one trials met the inclusion criteria (n = 7024 in pairwise analyses). Across 16 placebo-controlled trials, a higher proportion of participants achieved weight loss with GLP- 1-based agents than with placebo: 78.54% (3231/4114) versus 26.53% (772/2910); pooled odds ratio: 11.37 (95% confidence interval: 8.10-15.98), P < .0001; I2 = 82%. In the network meta-analysis, tirzepatide and semaglutide ranked highest (surface under the cumulative ranking curve 91.2% and 85.4%, respectively). CONCLUSION: GLP-1 receptor agonists significantly increase the likelihood of weight loss versus placebo, with tirzepatide and semaglutide demonstrating the greatest relative efficacy among agents evaluated. These findings support GLP-1-based therapy as an effective component of clinical obesity management.