A team led by researchers at Mayo Clinic have used proprietary algorithms and genetic data to develop a risk score that predicts which patients are most likely to experience GI side effects from GLP-1 agonists such as Wegovy and Zepbound. Such effects impact up to 70% of patients. Nausea is the most common reason people discontinue GLP-1s.
In this study, patients with certain genetic markers were more than twice as likely to experience nausea from GLP-1s compared to others (68% vs. 30%). This score should help match patients to the right medications and give them a better chance of success. It also has implications in pharmaceutical development, improving participant selection and retention in clinical trials, and accelerating time to market.
Mayo Clinic physician and obesity expert Andres Acosta, MD, PhD is the senior author of the study, which was at Digestive Disease Week 2025. Their paper is currently a preprint. Acosta is also co-founder of Phenomix. The test used in this study was that company’s MyPhenome test.
The researchers analyzed post-hoc genetic data from 110 participants. Using a machine learning-assisted Genetic Risk Score, researchers analyzed the relationship between individual genetic profiles and adverse events, including nausea. Patients with a high GRS were more than twice as likely to experience nausea from liraglutide, a GLP-1 medication, compared to those with a low score (68% vs. 30%).
There are three key drivers of obesity-related hunger, Acosta told Inside Precision Medicine, “The hungry gut, the hungry brain, and emotional hunger. What we are learning is that response to GLP-1s depends on the type of hunger you experience.”
The best responders to GLP-1s, the researchers found, are those with the “hungry brain.”
“These findings represent a meaningful advancement in how we approach obesity treatment at an individual level,” said Acosta. “By identifying which patients are more likely to experience side effects before starting therapy, we can improve tolerability, support long-term adherence, and better match the right treatment to the right patient. This is a critical step toward delivering on the promise of truly personalized obesity care.”
Previous research presented by Phenomix at DDW 2024 demonstrated that Phenomix’s MyPhenome test can identify patients more likely to respond to semaglutide.
MyPhenome is a saliva swab-based test that looks for the root biological factors that can cause obesity and helps physicians personalize treatments for more effective weight loss. These latest findings address the patients who may see optimal weight loss but still experience treatment-limiting side effects.
“Our team’s research builds on previous findings by showing we can now predict not just who will benefit from GLP-1s, but who is more likely to struggle with side effects,” said co-author Thomas Fredrick, MD. “That allows for more balanced, individualized treatment planning. It’s an important advancement in the clinical application of precision obesity medicine.”
“This study underscores the power of predictive tools like MyPhenome to transform how we approach obesity treatment — not just in the clinic, but in the drug development pipeline,” said Mark Bagnall, CEO of Phenomix. “By identifying patients at risk for side effects before treatment begins, we can match the right patient to the right therapy, increase real-world adherence, and dramatically improve clinical trial efficiency through smarter patient selection.”
