Genetic Marker Identified as Predictor of Weight Loss Response to GLP-1RAs

Recent research conducted by Cleveland Clinic researchers has uncovered a genetic factor that influences how individuals respond to GLP-1 receptor agonists (GLP-1RAs), a class of medications such as liraglutide and semaglutide commonly used for weight management. Published in the journal Diabetes, Obesity and Metabolism, the study explores the role of the gene neurobeachin (NBEA) in personalized obesity treatment.

The study analyzed extensive real-world data from the NIH All of Us cohort and the UK Biobank, revealing that genetic variations in NBEA—a gene encoding a protein kinase A anchor protein—significantly impact weight loss outcomes. Participants with specific genetic profiles, labeled as 'responsive' NBEA genotypes, were up to 82% more likely to experience notable weight loss with GLP-1RA therapy. Conversely, those with 'non-responsive' genotypes had a 50% higher chance of not losing weight despite treatment.

This discovery highlights the potential for tailored obesity treatments, where genetic testing could identify individuals most likely to benefit from GLP-1RA drugs. Such personalized approaches may enhance efficacy, reduce trial-and-error prescribing, and improve overall treatment outcomes.

The findings are validated across multiple cohorts, strengthening their reliability and paving the way for integrating genetic insights into clinical decision-making. As the field advances, these developments could lead to more targeted and effective strategies for tackling obesity.

For further details, refer to the publication: Arshiya Mariam‐Smith et al, Neurobeachin (NBEA) is a novel gene associated with GLP-1 receptor agonist related weight loss, Diabetes, Obesity and Metabolism, 2025. Source: https://medicalxpress.com/news/2025-07-genetic-predictor-weight-loss-glp.html