Some people, frustratingly, don’t lose as much weight as others on popular weight-loss drugs like Wegovy. A new study suggests the answer may be in their genes.

Researchers from consumer gene-testing service 23andMe, which has one of the world’s biggest DNA databases derived from saliva samples, analyzed genetic data from 27,885 customers who have taken drugs like Wegovy and Zepbound to see if any genes or variants were correlated with how much weight people lost or how bad their side effects were.

The findings, published online Wednesday by the journal Nature, showed people with a common gene variant lost more weight on GLP-1 weight-loss drugs than those without it. Researchers also found people with specific genetic variants were more likely to have side effects like nausea and vomiting from the drugs.

“This warrants further study,” said Dr. Noura Abul-Husn, chief medical officer at the 23andMe Research Institute. “Right now the alternative is really nothing to guide any type of personalization around how to manage expectations around GLP-1 use.”

23andMe filed for bankruptcy protection last year after struggling to find a profitable business model. Testing for predictive genes could be a way for the company to salvage its business.

23andMe is adding testing for weight-loss drug responsiveness to one of its health services in the hope that this testing becomes commonplace for people to manage their expectations around how much weight they will lose on the drugs. With newer weight-loss drugs potentially getting approved in coming years, this type of testing could one day guide people’s choices of which drug to take.

Some doctors think that gene testing to predict a patient’s response to weight-loss drugs could become as routine as what is done for other diseases like breast cancer.

Dr. Andres Acosta, a gastroenterologist at the Mayo Clinic, said it is valuable information because many patients pay several hundred dollars out of pocket for the drugs.

“We may know who needs this expensive medication and who may not respond and need another option,” said Acosta, who is a co-founder of Phenomix Sciences, a Mayo spinout that sells a gene test designed to predict responses to weight-loss treatments.

Weight-loss drugs like Novo Nordisk’s Ozempic and Wegovy and Eli Lilly’s Mounjaro and Zepbound work by mimicking gut hormones including GLP-1, suppressing appetite and making people feel full sooner when eating.

They can help people lose up to more than 20% of their body weight, but some people don’t lose nearly that much. Doctors say roughly 10% to 15% of people who try the drugs lose less than 5% of their body weight. Known side effects include nausea and vomiting, but not everyone experiences those equally, either.

Underlying medical conditions, age and other factors likely explain some of the variations in responses, but doctors have also suspected genetic differences might play a role too.

23andMe’s researchers found that a variant in the GLP1R gene was associated with a modest amount of additional weight loss from GLP-1 drugs. The GLP1R gene has the code for the GLP-1 receptors in the body that drugs like Ozempic and Wegovy target.

People with GLP1R variants lost up to about 3.3 pounds more than those who didn’t have the variant and were more likely to experience vomiting and nausea. The median overall weight loss among people taking GLP-1 drugs in the study was about 25 pounds.

This variant is relatively common, found in about 40% of people of European descent and 38% of people with Middle Eastern ancestry. It is least common in people of African ancestry, at around 7%.

A different variant, on the GIPR gene, was associated specifically with a greater likelihood of side effects from Lilly’s Mounjaro and Zepbound, the study showed. Those drugs also target the GIP hormone in addition to GLP-1.

The findings still leave some mystery behind the variation in how much weight people lose on GLP-1s. The genetic factors and known nongenetic factors only explain some of the variation, Ruth J.F. Loos, a professor at the University of Copenhagen’s Novo Nordisk Foundation Center for Basic Metabolic Research, wrote in an accompanying commentary in Nature. More work is needed to uncover the factors behind the rest of the variation, she wrote.

While the study presented interesting clues, it is too early to move toward genetic testing for GLP-1 use, said Dr. Marie Spreckley, a postdoctoral researcher at the University of Cambridge working on obesity treatments.

“Overall, this is an important step towards understanding variability and the potential for future precision approaches,” she said. “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.”

Write to Peter Loftus at Peter.Loftus@wsj.com

Some people, frustratingly, don’t lose as much weight as others on popular weight-loss drugs like Wegovy. A new study suggests the answer may be in their genes.

Researchers from consumer gene-testing service 23andMe, which has one of the world’s biggest DNA databases derived from saliva samples, analyzed genetic data from 27,885 customers who have taken drugs like Wegovy and Zepbound to see if any genes or variants were correlated with how much weight people lost or how bad their side effects were.

The findings, published online Wednesday by the journal Nature, showed people with a common gene variant lost more weight on GLP-1 weight-loss drugs than those without it. Researchers also found people with specific genetic variants were more likely to have side effects like nausea and vomiting from the drugs.

“This warrants further study,” said Dr. Noura Abul-Husn, chief medical officer at the 23andMe Research Institute. “Right now the alternative is really nothing to guide any type of personalization around how to manage expectations around GLP-1 use.”

23andMe filed for bankruptcy protection last year after struggling to find a profitable business model. Testing for predictive genes could be a way for the company to salvage its business.

23andMe is adding testing for weight-loss drug responsiveness to one of its health services in the hope that this testing becomes commonplace for people to manage their expectations around how much weight they will lose on the drugs. With newer weight-loss drugs potentially getting approved in coming years, this type of testing could one day guide people’s choices of which drug to take.

Some doctors think that gene testing to predict a patient’s response to weight-loss drugs could become as routine as what is done for other diseases like breast cancer.

Dr. Andres Acosta, a gastroenterologist at the Mayo Clinic, said it is valuable information because many patients pay several hundred dollars out of pocket for the drugs.

“We may know who needs this expensive medication and who may not respond and need another option,” said Acosta, who is a co-founder of Phenomix Sciences, a Mayo spinout that sells a gene test designed to predict responses to weight-loss treatments.

Weight-loss drugs like Novo Nordisk’s Ozempic and Wegovy and Eli Lilly’s Mounjaro and Zepbound work by mimicking gut hormones including GLP-1, suppressing appetite and making people feel full sooner when eating.

They can help people lose up to more than 20% of their body weight, but some people don’t lose nearly that much. Doctors say roughly 10% to 15% of people who try the drugs lose less than 5% of their body weight. Known side effects include nausea and vomiting, but not everyone experiences those equally, either.

Underlying medical conditions, age and other factors likely explain some of the variations in responses, but doctors have also suspected genetic differences might play a role too.

23andMe’s researchers found that a variant in the GLP1R gene was associated with a modest amount of additional weight loss from GLP-1 drugs. The GLP1R gene has the code for the GLP-1 receptors in the body that drugs like Ozempic and Wegovy target.

People with GLP1R variants lost up to about 3.3 pounds more than those who didn’t have the variant and were more likely to experience vomiting and nausea. The median overall weight loss among people taking GLP-1 drugs in the study was about 25 pounds.

This variant is relatively common, found in about 40% of people of European descent and 38% of people with Middle Eastern ancestry. It is least common in people of African ancestry, at around 7%.

A different variant, on the GIPR gene, was associated specifically with a greater likelihood of side effects from Lilly’s Mounjaro and Zepbound, the study showed. Those drugs also target the GIP hormone in addition to GLP-1.

The findings still leave some mystery behind the variation in how much weight people lose on GLP-1s. The genetic factors and known nongenetic factors only explain some of the variation, Ruth J.F. Loos, a professor at the University of Copenhagen’s Novo Nordisk Foundation Center for Basic Metabolic Research, wrote in an accompanying commentary in Nature. More work is needed to uncover the factors behind the rest of the variation, she wrote.

While the study presented interesting clues, it is too early to move toward genetic testing for GLP-1 use, said Dr. Marie Spreckley, a postdoctoral researcher at the University of Cambridge working on obesity treatments.

“Overall, this is an important step towards understanding variability and the potential for future precision approaches,” she said. “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.”

Write to Peter Loftus at Peter.Loftus@wsj.com