Genetic Variants Linked to Weight Loss Outcomes on GLP-1 Drugs in New Study

A new study reveals that specific genetic variants influence the effectiveness of weight-loss drugs such as semaglutide (Wegovy, Ozempic) and tirzepatide (Mounjaro). Researchers analyzed genetic data from individuals who self-reported their experiences with these GLP-1 receptor agonist medications.

The findings indicate that variations in genes related to appetite and digestion can lead to differences in weight loss and side effects.

The study, published in the journal Nature, examined data from 15,000 people who had undergone genetic testing through 23andMe and reported using weight-loss drugs. 7% of their body weight over approximately eight months of treatment. Weight loss ranged from little or nothing to as much as 30% in some cases.

One genetic variant, rs10305420 in the GLP1 receptor gene, was associated with increased weight loss among users of GLP-1 drugs. 76 kg on average, with those having two copies experiencing double the effect. This variant is more prevalent in people of European ancestry, where 64% carry one copy and 16% carry two copies, compared to 7% of African Americans carrying one copy.

Another variant, rs1800437 in the gastric inhibitory polypeptide receptor gene, was linked to higher rates of nausea and vomiting in users of tirzepatide.

This side effect could be up to 15 times more severe in affected individuals, potentially impacting 1% of users. The study suggests these genetic associations partially explain why responses to the drugs vary widely. > "The study found a genetic variant associated with weight loss, which was also associated with nausea.

“— Professor Ruth Loos, University of Copenhagen, as reported in Nature (2023)”