Comparative Efficacy of GLP-1 Receptor Agonists, Exercise, and Their Combination on Body Composition and Glucolipid Metabolism in Adults With Overweight or Obesity: A Network Meta-Analysis of Randomized Controlled Trials.

Abstract

The paper aims to assess the effects of GLP-1 RAs, structured exercise, and their combination on body composition and cardiometabolic outcomes in adults with overweight or obesity. PubMed, Web of Science, Scopus, and EBSCO were searched through April 2026 for English-language RCTs using terms related to obesity, GLP-1 RAs, exercise, and glucolipid metabolism outcomes. We included RCTs of adults (18-65 years, BMI ≥ 25 kg/m²) without major comorbidities, except for type 2 diabetes, testing GLP-1 RAs, structured exercise, or both. Of 2508 screened articles, nine studies comprising 1009 participants met eligibility criteria. Participants included 589F/420M, with a weighted mean age of 43.8 ± 12.2 years and weighted mean BMI of 32.6 ± 3.0 kg/m². Risk of bias was assessed using RoB 2. A frequentist random-effects model calculated SMDs. Primary outcomes were changes in body weight, waist-to-hip ratio, and fat mass. Secondary outcomes included fasting glucose, HOMA-IR, triglycerides, LDL-C, and HDL-C. Meta-regression assessed weight loss as a predictor of metabolic outcomes. The combination of GLP-1 receptor agonists and exercise was associated with the greatest effects on weight (SMD -1.04; 95% CI -1.24 to -0.83), fat mass (SMD -1.01; 95% CI -1.27 to -0.75), and waist-to-hip ratio (SMD -0.55; 95% CI -0.91 to -0.18) compared with placebo. For fasting glucose, the SMD was -0.49 (95% CI -1.52 to 0.55); for HOMA-IR, -0.59 (95% CI -0.89 to -0.29). For lipid outcomes, no statistically significant differences were observed for triglycerides or LDL-C, whereas HDL-C increased compared with placebo (SMD 0.32; 95% CI 0.04 to 0.61). Confidence in the evidence was high for body weight and fat mass, moderate for waist-to-height ratio and most lipid outcomes, and very low for fasting glucose. Combined GLP-1 RA and structured exercise interventions improved weight, insulin sensitivity, and selected lipid parameters more than monotherapies or placebo.