A study revealed that approximately 1 in 7 people using semaglutide—marketed for weight loss under the brand name Wegovy—for over a year, failed to lose at least 5% of their starting weight, indicating limited effectiveness for a subset of users.
New research suggests that genetic factors may hold the key to understanding these differences. A recent study indicates that a genetic risk score test could help predict whether an individual is likely to succeed with injected weight loss medications.
“We believe the test can identify who will 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 co-developed the test.
Named MyPhenome, the test was developed by Mayo Clinic researchers and licensed last year by Phenomic Sciences. It costs $350 and must be ordered by a healthcare provider.
The test examines 6,000 variations in 22 genes involved in the GLP-1 hormone signaling pathway. Based on the results, it assigns a risk score classifying individuals as either “hungry gut”-positive or “hungry gut”-negative.
People classified as hungry gut-positive exhibit normal responses to hormone signaling in the brain, while those who are hungry gut-negative do not respond as effectively to hormonal signals from the stomach that communicate satiety to the brain. According to Acosta, individuals classified as having a hungry brain may require different types of interventions, such as bariatric surgery.
A recent small study involving 84 participants from a weight loss registry at the Mayo Clinic applied this test to stored blood or saliva samples. After nine months on semaglutide, individuals identified as hungry gut-positive lost significantly more weight compared to 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 average 10% weight loss observed in hungry gut-negative participants.
The study’s findings are set to be presented at the Digestive Disease Week conference in Washington, DC. However, as the research has not yet undergone peer review or been published in a medical journal, its conclusions are considered preliminary.
“We need to validate these findings in a randomized, double-blind, placebo-controlled trial, which is the gold standard for clinical research,” Acosta emphasized.
“But at this point, we can confirm that these outcomes were observed in patients who were blinded to their classification as either hungry gut-positive or -negative during the trial,” he added, indicating that participants were unaware of their genetic classification while using the medication.
