Sex Differences in the Efficacy of Glucagon-Like Peptide-1 Receptor Agonists for Weight Reduction: A Systematic Review and Meta-Analysis.

AIM: To verify sex differences of GLP-1RAs for weight reduction. METHODS: We searched RCTs reporting weight change by sex from PubMed, Web of Science, Embase, Cochrane Library, and ClinicalTrials registries. Meta-regression was performed to evaluate the association between weight reduction and sex differences. Subgroup analyses were stratified by individual GLP-1RA medications, dose, treatment duration, indication, type of control, background treatment, and baseline weight. The study protocol was registered (CRD42023480167). RESULTS: Fourteen studies covering dulaglutide, exenatide, liraglutide, semaglutide, and retatrutide were included in this study. The meta-analysis showed that females lost more weight than males (MD 1.04 kg [95% CIs 0.70-1.38]; MD 1.69% [95% CI 0.78-2.61]). The pooled results of GLP-1RAs indicated similar results (MD 0.88 kg [95% CIs 0.67-1.09]). Meta-regression illustrated that substantial weight reduction was significantly relevant to greater gender differences (β = -0.19 [95% CIs -0.29 to -0.09]). Subgroup analysis demonstrated that indications for weight reduction increased the gender difference in weight reduction (MD 4.21 kg [95% CIs 1.75-6.67]). Background treatment, dose, duration of treatment, baseline weight, and type of control had no subgroup differences in the sex difference in weight reduction of GLP-1RAs. Dulaglutide (MD 0.88 kg [95% CIs 0.63-1.12]) and semaglutide (MD 1.04 kg [95% CIs 0.45-1.63]) showed statistically significant differences in weight reduction between males and females. No gender difference was observed in the exenatide subgroup analysis. CONCLUSIONS: Females lost more weight than males when treated with GLP-1RAs for weight reduction. The sex difference in weight reduction became more pronounced as the degree of weight reduction increased. Indications for obesity could magnify this sex difference.