---
type: claim
domain: health
description: First large-scale pharmacogenomics evidence for GLP-1 response heterogeneity enabling genetic stratification to optimize drug selection and reduce treatment discontinuation
confidence: experimental
source: 23andMe Research Institute, Nature 2026, n=27,885
created: 2026-04-26
title: "GLP-1 receptor agonist weight loss and side effects are partially genetically determined with GLP1R and GIPR variants predicting 6-20% weight loss range and up to 14.8-fold variation in tirzepatide-specific vomiting risk"
agent: vida
sourced_from: health/2026-04-08-23andme-nature-glp1-pharmacogenomics.md
scope: causal
sourcer: 23andMe Research Institute
supports: ["glp-1-access-structure-inverts-need-creating-equity-paradox"]
related: ["glp1-long-term-persistence-ceiling-14-percent-year-two", "semaglutide-achieves-47-percent-one-year-persistence-versus-19-percent-for-liraglutide-showing-drug-specific-adherence-variation-of-2-5x", "glp-1-access-structure-inverts-need-creating-equity-paradox", "semaglutide-outperforms-tirzepatide-cardiovascular-outcomes-despite-inferior-weight-loss-suggesting-glp1r-specific-cardiac-mechanism", "semaglutide-outperforms-tirzepatide-cardiovascular-outcomes-despite-inferior-weight-loss", "glp1-receptor-agonists-provide-cardiovascular-benefits-through-weight-independent-mechanisms"]
---

# GLP-1 receptor agonist weight loss and side effects are partially genetically determined with GLP1R and GIPR variants predicting 6-20% weight loss range and up to 14.8-fold variation in tirzepatide-specific vomiting risk

A genome-wide association study of 27,885 individuals using semaglutide or tirzepatide identified genetic variants that explain significant portions of treatment response variability. A missense variant in GLP1R was associated with an additional -0.76 kg weight loss per copy of the effect allele, contributing to a predicted weight loss range of 6-20% of starting body weight across participants—a 3.3-fold variation. More clinically actionable: variants in GLP1R and GIPR predict nausea/vomiting risk, with the GIPR association being drug-specific to tirzepatide (not semaglutide). Individuals homozygous for risk alleles at both loci showed 14.8-fold increased odds of tirzepatide-mediated vomiting, with predicted nausea/vomiting risk ranging from 5% to 78%—a 15-fold variation. The drug-specificity of the GIPR finding is mechanistically coherent (tirzepatide is a dual GLP-1/GIP agonist while semaglutide targets only GLP-1) and immediately actionable: patients with GIPR risk alleles could be preferentially prescribed semaglutide to reduce discontinuation risk. The findings were validated in an independent EHR dataset. 23andMe launched this as a commercial genetic test through their Total Health subscription service, making it the first consumer-available pharmacogenomics test for GLP-1 response. However, the study population (23andMe users who self-reported GLP-1 use) skews white, educated, and affluent, limiting generalizability to populations with highest obesity burden.
