Genetic Variants in the GLP-1 Receptor Affect How Well Oral Semaglutide Works

Two GLP-1 receptor gene variants (rs6923761 and rs761387) influence the clinical response to oral semaglutide in type 2 diabetes patients.

Candido, Riccardo et al.·Acta diabetologica·2026·
RPEP-149312026RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
Not classified
Evidence
Not graded
Sample
Not reported

What This Study Found

GLP1R polymorphisms rs6923761 and rs761387 significantly influenced clinical response to oral semaglutide in a retrospective cohort of T2DM patients.

Key Numbers

How They Did This

Retrospective cohort study of adult T2DM patients on oral semaglutide, genotyped for GLP1R rs6923761 and rs761387 polymorphisms and assessed for treatment response.

Why This Research Matters

Pharmacogenomics could allow personalized GLP-1 drug prescribing, ensuring patients receive the medication most likely to work for their genetic profile.

The Bigger Picture

This moves GLP-1 therapy toward precision medicine, where genetic testing guides drug selection rather than trial-and-error prescribing.

What This Study Doesn't Tell Us

Retrospective design with likely modest sample size. Single oral formulation studied — results may not apply to injectable semaglutide. Ethnic/population genetics may vary.

Questions This Raises

  • ?Should GLP-1 receptor genotyping become standard before prescribing?
  • ?Do these variants also affect response to injectable GLP-1 drugs or tirzepatide?

Trust & Context

Key Stat:
2 SNPs affect response GLP1R rs6923761 and rs761387 variants influenced oral semaglutide efficacy
Evidence Grade:
Retrospective pharmacogenomic cohort — provides initial evidence for genetic influences on drug response but needs prospective validation.
Study Age:
Published in 2026; advances pharmacogenomics of GLP-1 therapy.
Original Title:
Influence of GLP1 receptor rs6923761 and rs761387 genetic variants on oral semaglutide response in patients with type 2 diabetes.
Published In:
Acta diabetologica, 63(2), 303-311 (2026)
Database ID:
RPEP-14931

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled Trial
Cohort / Case-Control
Cross-Sectional / ObservationalSnapshot without intervening
This study
Case Report / Animal Study
What do these levels mean? →

Frequently Asked Questions

Why does semaglutide work better for some people?

Genetic variations in the GLP-1 receptor itself can change how well the drug binds and activates the receptor. This study found two specific gene variants that affect oral semaglutide response.

Should I get genetic testing before starting semaglutide?

Not yet — this research is still early. In the future, genetic testing may help doctors choose the best weight loss or diabetes medication for your specific genetic profile.

Read More on RethinkPeptides

Related articles coming soon.

Cite This Study

RPEP-14931·https://rethinkpeptides.com/research/RPEP-14931

APA

Candido, Riccardo; Toffoli, Barbara; Baccichetto, Gabriele; Marchese, Francesca; Carpenè, Silvia; Gaiotti, Sara; Fabris, Bruno; Bernardi, Stella. (2026). Influence of GLP1 receptor rs6923761 and rs761387 genetic variants on oral semaglutide response in patients with type 2 diabetes.. Acta diabetologica, 63(2), 303-311. https://doi.org/10.1007/s00592-025-02626-9

MLA

Candido, Riccardo, et al. "Influence of GLP1 receptor rs6923761 and rs761387 genetic variants on oral semaglutide response in patients with type 2 diabetes.." Acta diabetologica, 2026. https://doi.org/10.1007/s00592-025-02626-9

RethinkPeptides

RethinkPeptides Research Database. "Influence of GLP1 receptor rs6923761 and rs761387 genetic va..." RPEP-14931. Retrieved from https://rethinkpeptides.com/research/candido-2026-influence-of-glp1-receptor

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.