Your Genes and Sex Affect How Well Semaglutide Works for Severe Obesity
A GLP1R gene variant (rs6923761) and sex significantly influence semaglutide response in severe obesity, with homozygous GG patients and women losing weight faster.
Quick Facts
What This Study 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.
Key Numbers
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 They Did This
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.
Why This Research 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 Bigger Picture
Personalized medicine for obesity is becoming reality. Genetic testing could eventually guide which patients are prescribed GLP-1 drugs versus other treatments.
What This Study Doesn't 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.
Questions This Raises
- ?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?
Trust & Context
- Key Stat:
- 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
- Evidence Grade:
- Prospective pharmacogenomic study — well-designed but small, especially for the rare AA genotype (n=9). Needs replication in larger cohorts.
- Study Age:
- Published in 2025, among the first pharmacogenomic studies of semaglutide response in severe obesity.
- Original Title:
- A GLP1R gene variant and sex influence the response to semaglutide treatment in patients with severe obesity.
- Published In:
- Obesity (Silver Spring, Md.), 33(7), 1237-1242 (2025)
- Authors:
- Phan, Aurélie(2), Carette, Claire(2), Narjoz, Céline, Rives-Lange, Claire, Rassy, Nathalie, Czernichow, Sebastien, Pallet, Nicolas
- Database ID:
- RPEP-13043
Evidence Hierarchy
Watches what happens naturally without intervening.
What do these levels mean? →Frequently Asked 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 More on RethinkPeptides
Cite This Study
https://rethinkpeptides.com/research/RPEP-13043APA
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
MLA
Phan, Aurélie, et al. "A GLP1R gene variant and sex influence the response to semaglutide treatment in patients with severe obesity.." Obesity (Silver Spring, 2025. https://doi.org/10.1002/oby.24300
RethinkPeptides
RethinkPeptides Research Database. "A GLP1R gene variant and sex influence the response to semag..." RPEP-13043. Retrieved from https://rethinkpeptides.com/research/phan-2025-a-glp1r-gene-variant
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.