Weight Reduction Heterogenicity and Mediators of GLP-1RAs and Dual Agonists for Individuals With Obesity: A...

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual agonists have become pivotal options for obesity, but marked weight loss heterogeneity remains poorly understood. This meta-regression analysis aimed to identify factors influencing this heterogeneity. We searched Medline, Embase, The Cochrane Library, and Web of Science up to February 1, 2026, enrolling 32 eligible trials (40 408 participants) following PRISMA guidelines. Meta-regression and subgroup analyses were performed using R software. Pooled analysis showed that GLP-1RAs and dual agonists achieved a weighted mean weight reduction of 9.36% (95% CI 7.92%-10.80%), with high interstudy heterogeneity (I² = 99.6%, p < 0.001). Subgroup analyses revealed that GLP-1/GIP dual agonists (tirzepatide) and longer treatment duration (≥ 72 weeks) yielded superior weight-lowering effects. Meta-regression demonstrated that baseline anxiety/depression was positively associated with weight loss efficacy (β = 2.44, p < 0.001, R² = 81.34%). Comorbid Type 2 diabetes mellitus (T2DM), obstructive sleep apnea (OSA) and metabolic dysfunction-associated fatty liver disease (MAFLD) were negatively correlated with treatment response (all p < 0.05). Emotional state and metabolic comorbidities including T2DM, OSA and MAFLD are important influencing factors of the interindividual differences of weight loss efficacy of GLP-1RAs and dual agonists, providing evidence for personalized obesity management.