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Study breakdown

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

RPEP-149312026Candido, Riccardo; Toffoli, Barbara; Baccichetto, Gabriele; Marchese, Francesca; Carpenè, Silvia; Gaiotti, Sara; Fabris, Bruno; Bernardi, Stella
evidence
The takeaway

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

2 SNPs affect response

GLP1R rs6923761 and rs761387 variants influenced oral semaglutide efficacy

What the researchers found

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

Why it matters

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

How the study worked

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

What this study cannot 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.

How to read the evidence

Retrospective pharmacogenomic cohort — provides initial evidence for genetic influences on drug response but needs prospective validation.

When this study was published

Published in 2026; advances pharmacogenomics of GLP-1 therapy.

The bigger picture

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

Questions still open

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

Common 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 the original research

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

View on PubMed ↗Publisher’s paper ↗

Citation

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