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

Abstract

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.