Your Genes and Sex Affect How Well Semaglutide Works for Severe Obesity | Research

The takeaway

A GLP1R gene variant (rs6923761) and sex significantly influence semaglutide response in severe obesity, with homozygous GG patients and women losing weight faster.

1.64% vs. 1.02% per month
Common GG genotype patients lost weight 60% faster than rare AA variant patients on the same semaglutide dose

What the researchers found

GLP1R rs6923761 GG homozygotes lost 1.64%/month vs. 1.02%/month for AA variants on semaglutide 2.4 mg; sex also influenced response, with women responding better.

Why it matters

Pharmacogenomics could help predict which patients will respond best to expensive GLP-1 drugs, improving cost-effectiveness and reducing frustration from non-response.

The numbers in context

112 patients with BMI >= 40 on semaglutide 2.4 mg weekly for 4+ months. AA (8%): 1.64%/month weight loss. G carriers: 1.04%/month (P = 0.03). Women AA: 1.89%/month vs men G: less than half that rate.

How the study worked

Prospective genotyping study of 112 patients with grade 3 obesity treated with semaglutide 2.4 mg weekly for 4+ months, analyzing weight loss kinetics by GLP1R genotype and sex.

Who was studied

Adults with grade 3 obesity (BMI >= 40) on semaglutide

What this study cannot tell us

Small sample (n=112) with only 9 AA genotype patients. Short follow-up (4 months). Single gene variant studied — other variants likely also matter.

How to read the evidence

Prospective pharmacogenomic study — well-designed but small, especially for the rare AA genotype (n=9). Needs replication in larger cohorts.

When this study was published

Published in 2025, among the first pharmacogenomic studies of semaglutide response in severe obesity.

The bigger picture

Personalized medicine for obesity is becoming reality. Genetic testing could eventually guide which patients are prescribed GLP-1 drugs versus other treatments.

Questions still open

Should GLP1R genotyping be performed before starting semaglutide in severely obese patients?
Do other GLP1R variants influence response to tirzepatide and other GLP-1 drugs?

Common questions

Why do some people respond better to semaglutide than others?

Genetics plays a role. This study found that a variant in the GLP-1 receptor gene affects how well the drug works — patients with the common GG genotype lost weight about 60% faster than those with the AA variant.

Do men and women respond differently to semaglutide?

Yes, this study found women had a better weight loss response than men on semaglutide 2.4 mg, adding sex to genetics as a factor influencing treatment outcomes.

Read the original research

A GLP1R gene variant and sex influence the response to semaglutide treatment in patients with severe obesity.

Obesity (Silver Spring, Md.), 33(7), 1237-1242

View on PubMed ↗Publisher’s paper ↗

Citation

Phan, Aurélie; Carette, Claire; Narjoz, Céline; Rives-Lange, Claire; Rassy, Nathalie; Czernichow, Sebastien; Pallet, Nicolas. (2025). A GLP1R gene variant and sex influence the response to semaglutide treatment in patients with severe obesity.. Obesity (Silver Spring, Md.), 33(7), 1237-1242. https://doi.org/10.1002/oby.24300