April 08, 2026
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Genetics may help explain why some people have more success than others taking Ozempic and other GLP-1 weight-loss drugs, a new study says.
The onslaught of media coverage about blockbuster weight-loss drugs, such as Ozempic and Zepbound, may make it seem as though they work magic. But some people have little success losing weight with the drugs and experience significant side effects.
The reasons why people have such varied experiences has been unclear, though new research from the 23andMe genetic testing company suggests that two gene variants may help dictate who does well on GLP-1 weight-loss drugs.
MORE: Newly approved weight-loss pills could expand access to GLP-1s
The study, published Wednesday in the journal Nature, surveyed more than 27,000 people in the 23andMe genetic database about their responses to the GLP-1 drugs semaglutide (Ozempic and Wegovy) and tirzepatide (Mounjaro and Zepbound). The researchers identified two genetic variants: one associated with greater weight loss for both major classes of GLP-1s and another variant that linked to nausea and vomiting to tirzepatide.
"A lot of clinicians and patients don't seem to recognize that GLP-1s don't work in everybody," G. Caleb Alexander, an epidemiologist at Johns Hopkins Bloomberg School of Public Health, told the Washington Post. "It's not clear why a substantial minority of individuals don't lose weight when taking a GLP-1 – this is a question of tremendous scientific and clinical importance."
Alexander was not involved in the study.
The new research could help remove some of the guesswork of weight-loss treatment with these drugs by helping doctors "tailor care with greater precision from day one," said Dr. Noura Abul-Husn, chief medical officer of the 23andMe Research Institute. The previously publicly-traded company, which offered saliva-based genetic testing directly to consumers, filed for bankruptcy last year and became a nonprofit research institute.
The difference associated with one of the genetic variants identified and the amount of weight loss was only about three pounds. Many factors are involved in people's responsiveness to GLP-1s, including underlying medical conditions, age and other variables.
"Overall, this is an important step towards understanding variability and the potential for future precision approaches," Dr. Marie Spreckley, a postdoctoral researcher at the University of Cambridge working on obesity treatments, told the Wall Street Journal. "But the effects are modest and the evidence is not yet sufficient to support using genetic information to guide treatment decisions in routine clinical practice."
