A large study of 23andMe customers discovered variants in two genes playing a role in weight loss, as well as nausea and vomiting.
Some people’s genes influence the amount of weight they will lose and the side effects they will experience from taking GLP-1 medications, such as Ozempic and Zepbound.
Genetic testing company 23andMe conducted a study of more than 27,000 customers taking GLP-1 medications. These medications work by mimicking the action of GLP-1, a hormone that helps regulate blood sugar and appetite. People who carry a particular genetic variant of the GLP-1 receptor gene GLP1R lost more weight than those who do not carry this variant, researchers report April 8 Nature.
“The results we got made perfect biological sense,” says statistical geneticist Adam Auton, vice president of human genetics at the 23andMe research institute in Palo Alto, California. This is because the receptor is the target of GLP-1 mimicking drugs. The variant the researchers discovered could increase the amount of receptor protein on the surface of cells, giving the drug more targets, Auton says.
People who own one copy of the variant lost an additional 0.76 kilograms (1.7 pounds) over about eight months, while those with two copies of the variant lost about 1.5 kilograms (3.3 pounds) more than those without the variant. This variant accounts for about 10 percent of the difference in weight loss people experience with medications.
“It’s a small contribution to the weight difference between patients, but it’s important because of the importance of this gene,” says Andres Acosta, a physician scientist at the Mayo Clinic in Rochester, Minnesota. Acosta was not involved in the new study but is co-founder of Phenomix Sciences, a company headquartered in Menlo Park, Calif., that offers AI-based genetic testing for predict which medications to lose weight will work best for a patient.
Researchers found that the same genetic variant impacting weight loss also increases the likelihood that a person taking a GLP-1 drug will develop nausea and vomiting. That’s not always a bad thing, Auton says. “If you experience side effects such as nausea and vomiting, this may actually indicate that the medication is having an effect.”
People taking tirzepatide, sold under the brand name Zepbound, were more likely to have nausea and vomiting if they had a specific variant of a different gene called GIPR. The protein it produces is the target of GIP, another hormone involved in controlling blood sugar and appetite. THE GIPR the variant had no discernible effect on weight.
Unlike the semaglutide drugs Wegovy and Ozempic, tirzepatide targets both GLP-1 and GIP receptors. And people who have variants of both GLP1R And GIPR Genes are almost 15 times more likely to vomit when taking tirzepatide, the team found.
Genetics alone does not determine the effectiveness of medications, Auton says. But knowing which variants a person is carrying, he says, “can be very informative for people who are considering taking these medications. It can help them prepare for the type of experience they might have.”