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Meta-Analysis
. 2025 Mar;17(3):e70063.
doi: 10.1111/1753-0407.70063.

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

Yucheng Yang  1   2 , Liyun He  1   2 , Shumeng Han  1   2 , Na Yang  1   2 , Yiwen Liu  1   2 , Xuechen Wang  1   2 , Ziyi Li  1   2 , Fan Ping  1   2 , Lingling Xu  1   2 , Wei Li  1   2 , Huabing Zhang  1   2 , Yuxiu Li  1   2
Affiliations
Meta-Analysis

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

Yucheng Yang et al. J Diabetes. 2025 Mar.

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.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Flowchart of identification and selection of included studies for systematic review and meta‐analysis.
FIGURE 2
FIGURE 2
Forest plot for meta‐analysis of included studies. Results were summarized by individual studies. One trial might have over one dose or type of GLP‐1 RA treatments, and the data would be combined to a single dataset. (A) The unit of weight change is the kilogram; (B) the unit of weight change is the percentage. CI, confidential interval.
FIGURE 3
FIGURE 3
Association between the amount of weight reduction and gender differences in weight reduction of GLP‐1 RAs. Each circle represents individual study data. The size of each circle is indicative of its weight in the meta‐regression analysis and larger circles denote studies with greater influence on the overall result. The vertical axis measures the difference in weight reduction between females and males, with positive values signifying additional weight reduction observed in women compared to men. GLP‐1 RA, glucagon‐like peptide‐1 receptor agonists.
See this image and copyright information in PMC

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MeSH terms