Hormonal
Carrying the T allele of the GLP1R missense variant rs10305420 (p.Pro7Leu) significantly increases weight loss efficacy in patients treated with GLP-1 receptor agonists, adding approximately 0.76 kg of weight loss per allele copy.
If you are taking a GLP-1 medication like semaglutide or tirzepatide, your genetics play a role in how much weight you lose. Specifically, a common genetic variant (rs10305420) is linked to better weight loss results. While this genetic effect is modest (adding less than 1 kg on average), it is a real biological factor. This suggests that genetic testing could eventually help doctors predict who will respond best to which drug, allowing for more personalized treatment plans rather than a one-size-fits-all approach.
We identify a missense variant in GLP1R that is associated significantly with increased efficacy of GLP1 medications (P = 2.9 × 10−10), with an additional −0.76 kg of weight loss expected per copy of the effect allele.
Why this rating
Large sample size (n=15,237 for GWAS), genome-wide significance, replication in an external EHR cohort (All of Us), but relies on self-reported data for the primary cohort.
Source
Genetic predictors of GLP1 receptor agonist weight loss and side effects
Qiaojuan Jane Su et al. · Nature · 2026
DOI 10.1038/s41586-026-10330-z
More from this paper
- A specific missense variant in the GIP receptor (GIPR, rs1800437, p.Glu354Gln) is associated with an increased risk of vomiting in patients treated with tirzepatide, but not semaglutide.Good
- Genetic variants in GLP1R that increase weight loss efficacy are also associated with an increased risk of nausea and vomiting, suggesting a link between efficacy and side effects.Moderate
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