23andMe Finds Genes Tied to GLP1 Drug Weight Loss

Researchers at the 23andMe Research Institute have identified genetic variants that help explain why some people lose more weight than others on popular obesity treatments like semaglutide and tirzepatide, according to a study published Wednesday in the journal Nature. The analysis, based on self-reported data from nearly 28,000 individuals who used these glucagon-like peptide 1 receptor agonist drugs, points to variations in the GLP1R and GIPR genes as key factors influencing both weight loss efficacy and side effects such as nausea and vomiting.

The study conducted a genome-wide association analysis to pinpoint these genetic signals. A missense variant in the GLP1R gene, known as rs10305420, was associated with greater weight loss. Carriers of one copy of the variant lost an average of 0.76 kilograms more per allele compared to non-carriers, while those with two copies saw roughly double that benefit. This variant, present in about 40 percent of people of European and Middle Eastern ancestry, may enhance the receptor's efficiency in responding to the drugs, potentially by improving its transport to cell surfaces. The findings also linked the variant to a higher risk of...