Study Identifies Genetic Variations Influencing Response to Weight-Loss Drugs Wegovy and Mounjaro

A study published in the journal Nature examined genetic factors influencing responses to weight-loss medications, including semaglutide (marketed as Wegovy and Ozempic) and tirzepatide (marketed as Mounjaro). The research analyzed data from 15,000 people who underwent genetic testing through 23andMe prior to obesity treatment. 7 percent of their body weight over about eight months.

Weight-loss results varied among individuals, with some losing up to 30 percent of their body weight and others showing minimal or no reduction. The study identified millions of genetic variants and linked specific patterns to drug effectiveness and side effects. These findings highlight genetic influences on treatment outcomes for obesity.

genetic variant associated with appetite and digestion was linked to greater weight loss and increased nausea.

76 kg more than those without it, with those having two copies experiencing double that amount. The variant's prevalence differs by ancestry: 64 percent of people with European ancestry carry one copy, 16 percent carry two copies, while only 7 percent of African Americans carry a copy.

“The study found a genetic variant associated with weight loss, which was also associated with nausea.”

Professor Ruth Loos, who commented on the research in Nature, noted that carriers of the variant lose more weight on average. Clinical trials have shown semaglutide typically results in about 14 percent weight loss, while tirzepatide achieves around 20 percent.

A separate genetic variant was identified that increases the risk of severe vomiting with tirzepatide, affecting up to 1 percent of patients and making reactions nearly 15 times worse than average. Professor Loos stated that the genetic influence is modest but comparable to other factors.

She emphasized the need for replication in additional studies, which have not yet been conducted. Beyond genetics, other elements affect treatment outcomes. Previous research indicates women are more than twice as likely as men to lose 15 percent of their body weight on Mounjaro.

Younger patients, as well as those who are white or Asian, tend to achieve greater weight loss, though reasons for these differences are unclear. Dr. Marie Spreckley from the University of Cambridge described genetics as one part of a complex picture, with behavioral, clinical, and treatment-related factors playing primary roles.

Professor Naveed Sattar from the University of Glasgow called the findings scientifically interesting but not yet ready to alter clinical practice. He stressed the need for more robust trial data on benefits and harms of these therapies. An estimated 1.6 million people in Britain have used weight-loss medications in the past year, mostly purchased privately through online pharmacies.

The stakes involve improving personalized treatments for obesity, which affects millions globally and raises health risks like diabetes and heart disease. Future studies could lead to genetic screening to optimize drug selection and minimize side effects.