CLEVELAND - A new study published by Cleveland Clinic researchers investigating the genetic underpinnings of weight loss response has identified a gene, neurobeachin (NBEA), as a predictor of how individuals respond to GLP-1RAs, the class of medications behind popular treatments like liraglutide and semaglutide.
While GLP-1RAs have shown promise in helping individuals lose weight, their effectiveness varies widely. This study, which analyzed large-scale real-world data from the NIH All of Us cohort and the UK Biobank, discovered that individuals with certain genetic variations of NBEA —a gene encoding a protein kinase A anchor protein— are significantly more likely to experience substantial weight loss—or, conversely, non-responsiveness—when prescribed GLP-1RAs. Findings were published in Diabetes, Obesity and Metabolism .
Key findings include:
- Individuals with a "responsive" NBEA genetic score were up to 82% more likely to achieve significant weight loss with liraglutide and semaglutide.
- Those with a "non-responsive" NBEA score were up to 50% more likely to not lose weight on liraglutide.
- Validation across two independent cohorts strengthens the reliability of these results.
This research paves the way for personalized obesity treatment strategies, allowing healthcare providers to use genetic insights to identify patients most likely to benefit from GLP-1RA medications.
"Over 40% of U.S. adults live with obesity, a major risk factor for more than 200 complications, including cardiometabolic diseases and cancers," said lead author Daniel Rotroff, PhD, Chair of Cleveland Clinic's Department of Quantitative Health Sciences. "These findings have the potential to advance obesity care and provide more effective, personalized treatment options."
