While GLP-1 analogs like semaglutide appear to work in both sexes, emerging evidence shows quantitative differences in how men and women respond, and research in women remains critically lacking.
Critical data gap in womenDespite the exploding popularity of GLP-1 drugs especially among women, female animal models and women remain severely underrepresented in GLP-1 research
What the researchers found
The review found no evidence for major qualitative sex differences in the therapeutic effects of clinically approved GLP-1 analogs — both men and women benefit from these drugs for obesity, diabetes, and cardiovascular disease. However, a growing body of literature identifies quantitative sex differences in the response to GLP-1 and its analogs, meaning the magnitude or specific mechanisms of action may differ between sexes.
Notably, there appears to be an interaction between GLP-1 therapeutics and estrogens, which could affect drug responses in women across different life stages. The review also addresses emerging data on GLP-1 analogs' effects on mood and reproductive function, where sex differences are particularly relevant.
Why it matters
GLP-1 analogs are among the most prescribed medications globally, and their use is growing fastest among women — particularly for weight loss. Yet the fundamental science behind how these drugs work has been predominantly studied in male animal models and male-dominated clinical trials. Understanding sex-specific responses is essential for optimizing treatment, predicting side effects, and ensuring equitable care. The estrogen interaction is particularly important for women at different reproductive stages.
How the study worked
This is a narrative review article that examines published preclinical (animal) and clinical (human) studies on sex differences in GLP-1 biology and GLP-1 analog therapeutics. The review covers the endogenous GLP-1 system, brain and behavioral effects on appetite and metabolism, clinical outcomes in obesity/diabetes/cardiovascular disease, and effects on mood and reproductive function.
What this study cannot tell us
As a review, this paper synthesizes existing literature rather than presenting new data. The review itself is limited by the very gap it identifies — insufficient research in female models means there is limited data to review. The authors acknowledge that the absence of evidence for sex differences is not evidence of absence, as many studies simply never tested for them. The narrative review format also means study selection may not be systematic.
How to read the evidence
This is a narrative review that synthesizes existing preclinical and clinical literature. Reviews provide valuable overviews but do not present new primary data. The strength of the conclusions is limited by the quality and quantity of the underlying studies, which the authors note is particularly thin for female-specific data.
When this study was published
Published in 2025, this is a very timely review given the rapid expansion of GLP-1 analog prescriptions and the increasing recognition of sex-based differences in pharmacology.
The bigger picture
This review highlights a systemic problem in biomedical research — the persistent underrepresentation of female subjects — applied to one of the most impactful drug classes of the decade. As GLP-1 analogs expand into new indications (cardiovascular disease, kidney disease, addiction), understanding sex-specific pharmacology becomes increasingly important. The estrogen-GLP-1 interaction also raises questions about how these drugs might behave differently in pre- vs. post-menopausal women, or during pregnancy.
Questions still open
- How does the interaction between GLP-1 analogs and estrogen affect drug efficacy and side effects across different stages of women's reproductive lives?
- Should dosing recommendations for semaglutide and tirzepatide be adjusted based on sex, given the quantitative differences in response?
- What are the effects of GLP-1 analogs on fertility and reproductive function in women, and how urgently does this need investigation given current prescribing patterns?
Common questions
Do GLP-1 drugs like Ozempic work as well for women as for men?
Should women on birth control or hormone therapy be concerned about interactions with GLP-1 drugs?
Read the original research
GLP-1 and Its Analogs: Does Sex Matter?
Endocrinology, 166(2)
Citation
Börchers, Stina; Skibicka, Karolina P. (2025). GLP-1 and Its Analogs: Does Sex Matter?. Endocrinology, 166(2). https://doi.org/10.1210/endocr/bqae165