Weight-loss shots that mimic gut hormones are getting more personalized—at least at the genetic level.
Some people’s genes can shape both how much weight they lose and what side effects they get while taking GLP-1 drugs, such as Ozempic and Zepbound. The new findings come from a large analysis by the genetic testing company 23andMe, using data from more than 27,000 customers who were taking these medications.
The study focuses on how GLP-1 drugs work. They mimic the action of GLP-1, a hormone that helps regulate blood sugar and appetite. Researchers report that people who carry a particular genetic variant of the GLP-1 receptor gene—GLP1R—tended to lose more weight than those who don’t carry that variant, with the results published April 8 in Nature.
Here’s where it gets more concrete. The variant may increase the amount of the receptor protein on the cell surface, which effectively gives the drug more “targets” to bind to. “The results that we got made perfect biological sense,” statistical geneticist Adam Auton, vice president of human genetics at the 23andMe Research Institute in Palo Alto, Calif, said. The logic is pretty straightforward: if the receptor is the drug’s target, biology is likely to care about genetic differences in that target.
In the real-world outcomes, people with one copy of the variant lost an additional 0.76 kilograms (1.7 pounds) over about eight months. Those with two copies lost about 1.5 kgs (3.3 pounds) more than people without the variant. The researchers say this variant accounts for about 10 percent of the difference in weight loss people experience on the drugs. It’s not the whole story—just a slice—but it’s a slice tied to a gene with clear significance.
There’s also a downside, or at least a tradeoff, depending on how you look at it. The same GLP1R variant that influenced weight loss also increases the likelihood that someone taking a GLP-1 drug will develop nausea and vomiting. Auton frames it in a slightly different way: nausea and vomiting can be a “signature” that the medication is having an effect. Not glamorous, sure—though if you’ve ever sat through an ultrasound appointment while your stomach churns a little, you know how distracting that sensation can be—but in this context it may actually track drug activity.
The picture expands when the team looked beyond pure GLP-1 approaches. 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, which makes the protein targeted by GIP, another hormone involved in blood sugar and appetite control. The GIPR variant didn’t show a discernable effect on weight. Since tirzepatide targets both the GLP-1 and GIP receptors, genetics starts to matter in combinations: people with variants in both GLP1R and GIPR genes have nearly 15 times increased odds of vomiting when taking tirzepatide, the team found.
Importantly, genetics alone doesn’t determine how well the drugs will work, Auton notes. Still, he says knowing which variants a person carries can be “quite informative” for individuals considering these medications, potentially helping them prepare for what the experience might be like. Andres Acosta, a physician scientist at the Mayo Clinic in Rochester, Minn., was not involved in the study but said the contribution is small—it’s still important because it connects to the significance of the gene. Acosta is also a cofounder of Phenomix Sciences, a company that offers AI-powered genetic tests aimed at predicting which weight loss medications will work best for a patient. Misryoum newsroom reports that the broader message is clear: the era of “one-size-fits-all” dosing may be giving way to a more biology-aware approach, even if it still can’t predict everything neatly at the individual level.
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