Nature
Some GLP-1 genetics results, but signal is small
Clinical takeaway: The test is already being marketed for use with a clinician despite limited usefulness. It’s part of an expensive 23andMe health package that some patients may use to support their GLP-1 experience.
It’s easy to imagine that genetics could eventually help guide GLP-1 use, but the current science doesn’t offer much insight. Research from 23andMe found that, even combined with demographic and clinical factors, genetic variation explains only about one-quarter of treatment response.
GLP-1 drugs produce widely variable results, from minimal weight loss to substantial reductions. This study examined whether genetics helps explain that variability.
Variants in the GLP1R gene were associated with greater weight loss. Variants in GLP1R and GIPR were also linked to nausea and vomiting, with one GIPR signal appearing specific to tirzepatide. This was a large GWAS based on data from 27,885 people who used GLP-1 medications. The associations are plausible, but effect sizes remain modest.
The combined model, integrating genetic, clinical, and demographic factors, explained about 25% of weight loss variability, with most of that driven by non-genetic inputs. Comorbidities, especially type 2 diabetes, fatty liver disease, and hypertension, were associated with lower weight loss. Model predictions aligned well with observed outcomes.
Clinical factors were more important than genetics. Greater weight loss was linked to higher dose, longer treatment duration, and use of tirzepatide vs semaglutide. Women and younger patients tended to have greater response, while type 2 diabetes was associated with less weight loss. These factors explained more variation than genetic differences.
“We believe these reports are a step forward in meeting an unmet need for a more informed and personalized approach to weight management,” said Dr. Noura Abul-Husn, MD, PhD, Chief Medical Officer at the 23andMe Research Institute. The company is already marketing the test for patients to use with a clinician.
The test is available to consumers as part of the company’s Total Health offering, priced at $499 for the first year and then $199 a year.
Source: Su QJ. Nature. 2026 Apr 8. Genetic predictors of GLP-1 receptor agonist weight loss and side effects