UNITED KINGDOM — A study of approximately 15,000 people in the United Kingdom taking semaglutide or tirzepatide found that variation in two genes linked to appetite and digestion is associated with greater weight loss and differences in side effects such as nausea and vomiting. Participants lost an average of 11.7% of their body weight over approximately eight months of treatment, though outcomes varied widely, with some losing up to 30% of their body weight while others lost little or no weight.

All study participants had previously undergone genetic testing through the company 23andMe, which provided data for the analysis. Researchers identified a pattern linking certain genetic variants to the effectiveness of weight-loss medications by analyzing millions of variants in participants' genomes. One genetic variant was found to increase average weight loss by approximately 0.76 kg (1.6 lbs), and people carrying two copies of the variant lost about twice as much weight as those with only one copy.

"The study found a genetic variant associated with weight loss, which was also associated with nausea," said Professor Ruth Loos of the University of Copenhagen. "People lose more weight if they have this variant," she added.

Among people of European ancestry, about 64% carry one copy of the variant and about 16% carry two copies. Approximately 7% of African Americans carry one copy. The study also identified another genetic variant potentially responsible for side effects such as nausea and vomiting in people taking tirzepatide. Up to 1% of people taking tirzepatide may experience severe vomiting associated with the variant, at rates nearly 15 times higher than normal.

Other factors also influence outcomes: women are more than twice as likely as men to lose 15% of their body weight when taking tirzepatide, and the type of medication, its dosage, and treatment duration have all been linked with greater weight loss.

Dr. Marie Spreckley of the University of Cambridge noted the limits of the findings. "Genetics is only one part of a much more complex picture," Spreckley said.

"Overall, these findings are scientifically interesting, but they are a long way from changing clinical practice," said Professor Naveed Sattar of the University of Glasgow. "What we really need now is more robust trial data to better define the balance of benefits and harms with these and many other emerging newer therapies," he added.

Clinical trials have indicated a mean weight loss of approximately 14% with semaglutide, marketed as Ozempic and Wegovy, and approximately 20% with tirzepatide, marketed as Mounjaro. At least 1.6 million people in the United Kingdom have tried weight-loss drugs in the past year, with most purchased privately through online pharmacies. The National Health Service offers Wegovy and Mounjaro only to a small percentage of people with obesity and related health issues.