Can a Saliva Test Tell You If GLP-1s Will Work for You?

The frenzy for GLP-1 drugs like Ozempic and Wegovy has created a multi-billion dollar market, with more people trying the expensive medications that the supply can support. But not everyone responds well to these injectables, which can make the financial investment even more painful.

Luckily, new research will be presented at Digestive Disease Week that shows that obesity phenotype testing may offer insight into who is the best candidate for GLP-1 drugs and who might be better served by a less expensive medicine.

What Is a Phenotype?

Obesity phenotypes are a relatively new concept, supported by the research of Andres Acosta, MD, PhD, associate professor of medicine at the Mayo Clinic and cofounder of Phenomix Sciences. The concept involves testing to determine whether patients fall into one of four obesity phenotypes:

• Hungry brain: The brain never reaches the feeling of fullness while eating (satiation)
• Emotional hunger: Eating as a response to emotional stress
• Hungry gut: The stomach empties rapidly, leaving patients hungry between meals (satiety)
• Slow burn: Burning calories at a slower-than-normal rate

With such varying types of hunger cues, Acosta and his colleagues posit that a blanket solution such as GLP-1s may not be the best solution for every person who struggles with weight loss. His most recent research tested a proprietary test offered by Phenomix Sciences called the MyPhenome Hungry Gut test.

The test, which uses a cheek swab to collect genetic material, was tested on 84 participants with obesity who were taking semaglutide, the active ingredient in medications like Wegovy, Ozempic, and Rybelsus. The test results were analyzed using a machine learning gene risk score (ML-GRS) to reveal whether a person was positive or negative for one of the obesity phenotypes: hungry gut.

Participants who were positive lost 19.5% of their total body weight, while those who were negative lost only 10%. While both are significant, people who were “hungry gut positive” were much more likely to have success on semaglutide.

“Our gut makes this hormone called GLP-1—it goes to the brain from our stomach and makes us feel full,” Acosta told Verywell. “But these patients eat a normal meal, and then want to eat again within an hour or two.”

GLP-1 medications work because they simulate the naturally-produced hormones for a continuous feeling of fullness. But for patients who do feel satiated in between meals, they may not have as impressive results, leading to dissatisfaction.

The Cost of Progress

Although GLP-1s have shown remarkable results, they are also very expensive and in short supply. Acosta said that the test, which is currently commercially available, will be a valuable tool for physicians as they prescribe medications to their patients. The test costs $500 out-of-pocket.

“We know from previous studies that if you don’t have that phenotype, you may not respond as well,” Acosta said. “If you have another phenotype, particularly hungry brain, there are other medications that are cost-effective at only $100 a month. What we are proposing is that not everyone needs to [be] taking expensive Ozempic or [other brands of] semaglutide.”

Cost is an ongoing issue, agrees Rekha Kumar, MD, associate professor of clinical medicine and attending endocrinologist at Weill Cornell Medicine and lead of medical affairs at Found.

“The tricky part is that an insurance company isn’t going to cover a non-FDA approved test that costs $500 to see if $1,000 medicine is going to work,” Kumar said. “Each generation of GLP-1 we see coming out seems to be effective for a larger percentage of the population.”

While the test may seem cost-prohibitive at the moment, Kumar said that there is likely a great audience for it—namely, physicians who don’t have the training that obesity management physicians use to customize treatments for their patients. She said that many endocrinologists use a combination of biomarkers, medical history, family history, and response to prior weight loss attempts to determine the best options for a patient’s medications.

“With a really good medical history, we can get pretty close if we’re sophisticated doctors,” Kumar said. “But as the number of clinicians grows that want to prescribe these drugs, but they don’t have the training, Dr. Acosta’s test could be more useful.”