Women are twice as likely to be hyper-responders to GLP-1 weight loss drugs in real-world analysis | Research

The takeaway

In 483 obesity patients on semaglutide/liraglutide, 33.8% were hyper-responders (>15% weight loss), with female sex the only significant predictor (OR 1.92)—diabetes, BMI, age, and mental health were not associated with response.

Women 2x more likely hyper-responders
Female sex was the only significant predictor of >15% weight loss on GLP-1 drugs—diabetes, BMI, age, and mental health were not associated

What the researchers found

Average TBWL: 12.2%. Hyper-responders (>15%): 33.8%. Non-responders (<5%): 17.8%. Female sex → hyper-response OR 1.92 (p=0.048). No association: diabetes, BMI, age, sedentary status, anxiety, depression.

Why it matters

Predicting who will respond best to expensive GLP-1 drugs is crucial for personalized prescribing. Finding that sex is the only significant predictor while common clinical factors are not challenges current assumptions.

How the study worked

Retrospective cohort of 483 adults (BMI ≥30) on semaglutide/liraglutide with ≥6 month follow-up (mean 17.3 months) at Vancouver obesity clinic. Multivariable logistic regression.

What this study cannot tell us

Retrospective. Canadian population. Multiple GLP-1 drugs pooled. OR for female sex just barely significant (CI 1.01-3.65). Novel biomarkers not assessed.

How to read the evidence

Retrospective cohort with multivariable regression. Good real-world evidence for a single predictive factor.

When this study was published

Published in 2025; data 2018-2021.

The bigger picture

The finding that women respond better to GLP-1 drugs aligns with emerging sex-based differences in metabolic drug response. Novel biomarkers are needed to predict response beyond clinical demographics.

Questions still open

Why do women respond better—hormonal, metabolic, or behavioral factors?
Could genetic or microbiome biomarkers better predict response?
Should GLP-1 drug dosing differ by sex?

Common questions

Can doctors predict who will respond to GLP-1 weight loss drugs?

Currently, prediction is limited. This study found that only being female significantly predicted a strong weight loss response. Common factors like diabetes, BMI, age, and mental health conditions did not predict response. About one-third of patients are hyper-responders (>15% weight loss) while about one in five has minimal response.

Do GLP-1 drugs work better for women?

This study suggests yes—women were about twice as likely to be hyper-responders (>15% weight loss). The reason is unclear but could involve hormonal differences, body composition, or metabolic factors. Average weight loss was 12.2% across all patients, which is clinically significant regardless of sex.

Read the original research

Factors associated with weight loss response to GLP-1 analogues for obesity treatment: a retrospective cohort analysis.

BMJ open, 15(1), e089477

View on PubMed ↗Publisher’s paper ↗

Citation

Squire, Peter; Naude, James; Zentner, Ali; Bittman, Jesse; Khan, Nadia. (2025). Factors associated with weight loss response to GLP-1 analogues for obesity treatment: a retrospective cohort analysis.. BMJ open, 15(1), e089477. https://doi.org/10.1136/bmjopen-2024-089477