A major question surrounding popular GLP-1 medications for weight loss is why some individuals experience significant weight loss, while others see minimal results. For example, about 1 in 7 people using semaglutide (marketed as Wegovy for weight loss) for over a year did not lose at least 5% of their starting weight, indicating the drug’s ineffectiveness for them.
Recent research suggests that the variability in response may be linked to genetic factors. A new study proposes that a genetic test assigning a risk score could help predict an individual’s likelihood of success with injected weight loss medications.
“We believe the test can determine who will lose weight and predict with 95% accuracy who will lose more than 5% using this genetic test,” said Dr. Andres Acosta, a gastroenterologist and researcher at the Mayo Clinic who co-developed the test.
Considering the high cost of these medications and their limited insurance coverage, being able to predict their effectiveness can save individuals significant frustration and expense.
The genetic test, MyPhenome, was developed by Mayo Clinic researchers and licensed by Phenomic Sciences. It costs $350 and must be ordered by a healthcare provider. The test examines 6,000 changes in 22 genes involved in the GLP-1 hormone signaling pathway, assigning a risk score that classifies individuals as “hungry gut”-positive or “hungry gut”-negative.
Individuals classified as hungry gut-positive have normal hormone signaling responses in the brain, while those classified as hungry gut-negative do not respond well to hormonal signals from the stomach that indicate fullness. These individuals, identified as having a “hungry brain,” might require different interventions like bariatric surgery to achieve weight loss.
In a small study involving 84 participants from a Mayo Clinic weight loss registry, researchers used stored blood or saliva samples for testing. After nine months on semaglutide, those classified as hungry gut-positive lost significantly more weight than those classified as hungry gut-negative.
After a year, hungry gut-positive individuals lost an average of 19% of their starting weight, nearly double the 10% average weight loss seen in hungry gut-negative individuals.
The study will be presented at the Digestive Disease Week conference in Washington, DC. However, its findings are preliminary as the study has not undergone external peer review or publication in a medical journal.
“We need to test these findings in a randomized, double-blinded, placebo-controlled trial, which is the gold standard,” Acosta said. “But for now, we can say these outcomes were from patients who were blinded to their classification while using the drug.”
