How a gene test could be the first step toward precision medicine for obesity

One of the big mysteries with popular GLP-1 medications for weight loss is why some people will lose 20% or more of their starting body weight on the drugs while for others, the scale will barely budge.

One study found that about 1 in 7 people who used semaglutide – which is approved for weight loss under the brand name Wegovy – for more than a year didn’t lose at least 5% of their starting weight, indicating that the drug didn’t work well for them.

Now, research suggests that the answer may lie in a person’s genes.

The study shows that a new test that assigns a genetic risk score may be able to help people figure out whether they are likely to be successful on injected weight loss medications.

“We think that the test will be able to explain who will be able to lose weight, and we can predict with 95% accuracy who will lose more than 5% with this genetic test,” said Dr. Andres Acosta, a gastroenterologist and researcher at the Mayo Clinic who helped develop the test.

Acosta points out that these medications aren’t cheap. They’re not always covered by insurance, and if they are, they may come with a high copay. Being able to predict whether the drugs will work could save people a lot of frustration and money.

The test, MyPhenome, was developed by researchers at the Mayo Clinic and was licensed last year by a company called Phenomix Sciences. It costs $350 and must be ordered by a health care provider.

It looks for 6,000 changes in 22 genes that lie in the signaling pathway for the GLP-1 hormone, and it uses the results to assign each person a risk score that classifies them as either “hungry gut”-positive or “hungry gut”-negative.

People who are hungry gut-positive have normal responses to hormone signaling in the brain, whereas people who are hungry gut-negative don’t seem to respond as well to hormonal signals from the stomach that tell the brain to stop eating. Acosta says the test classifies those people as having a hungry brain, and they may need different types of interventions to lose weight, such as bariatric surgery.

In a recent small study of 84 people enrolled in a weight loss registry at the Mayo Clinic, researchers ran the test on stored blood or saliva samples. After nine months on semaglutide, people who were classified as hungry gut-positive had lost significantly more weight than those were hungry gut-negative.

After a year, people classified as hungry gut-positive had lost an average of 19% of their starting weight, or nearly twice as much, on average, as the 10% of total body weight lost by people who were classified by the test as hungry-gut negative.

The study is slated to be presented Monday at the Digestive Disease Week conference in Washington, DC. It has not been scrutinized by outside experts or published in a medical journal, so its conclusions are considered preliminary.

“We do need to test these in a randomized, double blinded, placebo-controlled trial that we have done for other medications. That’s the highest gold standard,” Acosta said.

“But at this point, we can say that these outcomes were in patients who were blinded to the results as well as the investigation,” he added, meaning they didn’t know whether they were hungry gut-positive or -negative while they were using the drug.

Correction: A previous version of this story misspelled the name of Phenomix Sciences.

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