A recent comprehensive meta-analysis reveals that GLP-1 receptor agonists, popular medications for weight loss and type 2 diabetes management, deliver consistent results across most patient groups—with one notable exception: women tend to experience greater weight reduction than men.
A large-scale systematic review and meta-analysis published in JAMA Internal Medicine on March 2, 2026, examined data from 64 randomized clinical trials involving tens of thousands of participants. The study, led by researchers from the Johns Hopkins Bloomberg School of Public Health, assessed how factors such as sex, age, race, ethnicity, baseline body mass index (BMI), and hemoglobin A1c (HbA1c) influence the drugs’ effectiveness in promoting weight loss.
In six trials encompassing nearly 20,000 patients where outcomes were stratified by sex, women lost an average of 10.9% of their baseline body weight while using GLP-1 receptor agonists (GLP-1 RAs). Men, by comparison, lost about 6.8%. This difference proved statistically significant and highlights a meaningful variation in response.
By contrast, the analysis found no substantial differences in weight-loss outcomes across other key subgroups. Efficacy remained similar regardless of age (under 65 versus 65 and older), race, ethnicity, starting BMI, or baseline HbA1c levels. These findings draw from multiple trials: seven for age (4,314 patients), nine for race (25,229 patients), seven for ethnicity (8,328 patients), and others for BMI and HbA1c.
The reviewed trials primarily featured drugs like semaglutide (Ozempic, Wegovy), dulaglutide (Trulicity), liraglutide (Victoza, Saxenda), and exenatide, though tirzepatide (Mounjaro, Zepbound)—a dual GIP/GLP-1 agonist—was excluded due to its distinct mechanism.
Experts point to potential biological explanations for the sex-based difference. These include possible synergistic effects between GLP-1 agents and estrogen, variations in drug metabolism or processing in women’s bodies, and differences in average body weight or composition. Some researchers also suggest women may handle common side effects, such as nausea, more effectively, supporting better adherence and sustained results. However, the study was not designed to pinpoint exact mechanisms, and further research is needed.
Senior author Hemalkumar B. Mehta, PhD, an associate professor at Johns Hopkins, emphasized the broader implications. “These results should give clinicians and their patients more confidence that GLP-1 RAs work similarly well across different racial and ethnic populations, and different ages and weights, though they appear to have modestly greater effectiveness among women compared to men,” he noted in related coverage.
The consistency across diverse groups is particularly reassuring, given that clinical trials often underrepresent certain populations. While GLP-1 RAs have surged in popularity for their ability to achieve substantial and sustained weight reduction—along with benefits for heart health and blood sugar control—questions about equitable effectiveness have persisted amid high costs and demand.
Both men and women derive clinically meaningful benefits from these medications, and individual responses vary widely. Clinicians should continue tailoring treatment based on patient needs, while monitoring adherence, as discontinuation remains common.
This analysis underscores the value of ongoing research into subgroup responses to optimize use of these high-demand therapies.
Sources referenced:
- Alexander GC, et al. Heterogeneity of Treatment Effects of Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss in Adults: A Systematic Review and Meta-Analysis. JAMA Internal Medicine. Published online March 2, 2026. https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2845663
- Johns Hopkins Bloomberg School of Public Health. GLP-1 Weight-Loss Drugs Comparably Effective for Patients Across Age, Race, and Starting Weight. March 6, 2026. https://publichealth.jhu.edu/2026/glp-1-weight-loss-drugs-comparably-effective-for-patients-across-age-race-and-starting-weight
- MedPage Today. GLP-1 Drugs May Work Differently in Women. March 2, 2026. https://www.medpagetoday.com/endocrinology/obesity/120124
- Medscape. GLP-1 Weight Loss is Higher Among Women. March 6, 2026.
- Hub at Johns Hopkins. GLP-1 weight-loss drugs are comparably effective across age, race, and starting weight. March 3, 2026.