Genes may shape GLP‑1 response
Researchers are finding that genetic differences help explain why some people lose more weight on drugs like Ozempic and Mounjaro — one report cites a study that involved nearly 28,000 people. (earth.com)
These drugs copy gut hormones that tell the brain you are full, but a study in 27,885 users found DNA helps explain why weight loss varies so widely. (nature.com) Glucagon-like peptide 1 receptor agonists include semaglutide, sold as Ozempic and Wegovy, and tirzepatide, sold as Mounjaro and Zepbound. In the new Nature paper, researchers at 23andMe ran a genome-wide association study, scanning the genome for common variants tied to self-reported weight loss and side effects. (nature.com) The strongest signal was a missense variant in GLP1R, the gene that encodes the receptor targeted by these drugs. Each copy of that variant was linked to an extra 0.76 kilograms, or about 1.7 pounds, of weight loss during treatment. (nature.com) The study also linked variants in GLP1R and GIPR to nausea or vomiting, two of the most common reasons people stop these medicines. The GIPR signal showed up only in people taking tirzepatide, which hits both the glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide pathways. (nature.com; 23andme.com) Researchers said people on these drugs already show a wide spread in outcomes, with some losing less than 5% of body weight and others losing more than 20%. That spread has been visible in clinics even as average trial results for semaglutide and tirzepatide have looked strong. (23andme.com; nejm.org; cbsnews.com) In the 2021 STEP 1 trial, adults on semaglutide lost an average of 14.9% of body weight at 68 weeks, versus 2.4% with placebo. In a 2025 head-to-head trial reported by CBS from a New England Journal of Medicine paper, tirzepatide users lost about 20% over 72 weeks, compared with about 14% for semaglutide. (nejm.org; cbsnews.com) The new paper does not say genes are the whole story. The authors built a broader response model that also used demographic and clinical factors, and said the genetics could help sort patients by likely benefit and side-effect risk rather than predict outcomes on their own. (nature.com; 23andme.com) Outside experts said the findings point directly to the drug targets themselves. In a Nature News & Views article published April 8, Ruth Loos wrote that variants in GLP1R and GIPR offer clues to who responds differently and who may face adverse effects. (nature.com) There are limits. The Nature study relied on self-reported treatment experiences from 23andMe participants, and the effect size for the main GLP1R variant was modest, which means any future DNA test would need validation in clinical datasets before doctors use it to choose a drug. (nature.com; nature.com) For now, the finding is narrower than a promise and more useful than a hunch: the same genes that make the drug targets may help determine who loses more weight and who feels sick enough to quit. (nature.com)
