Genetic variations in the NBEA gene were associated with 82% higher odds of being a top weight-loss responder to GLP-1 receptor agonists like liraglutide.
82% more likelyPeople with favorable NBEA genetic scores were 82% more likely to be in the top 20% of weight loss responders on liraglutide.
What the researchers found
Individuals meeting the responsive NBEA genetic score threshold were 82% more likely to be highly responsive (top 20th percentile for weight loss) on liraglutide (FDR p = 1.8 × 10⁻⁶), validated in the UK Biobank (OR = 2.37, p = .008). For semaglutide, the responsive threshold showed OR = 1.63 in discovery and OR = 2.21 in validation. For non-responsiveness on liraglutide, the NBEA score predicted those with no weight loss (OR significant in both cohorts, p < .041), though the non-response score did not validate for semaglutide.
Why it matters
With GLP-1 receptor agonists costing thousands of dollars annually and not working equally for everyone, being able to predict who will respond best could save patients time, money, and frustration — and help healthcare systems allocate these medications more effectively through personalized prescribing.
How the study worked
The study used real-world data from the NIH All of Us cohort (N = 6,556) to develop a NBEA genetic score for weight loss at 12–18 months on GLP-1RAs, then independently validated it in the UK Biobank (N = 241). Logistic regression modeled associations between the genetic score and weight loss outcomes including high responsiveness and non-responsiveness.
What this study cannot tell us
The validation cohort (UK Biobank, N = 241) was relatively small compared to the discovery cohort. The non-response NBEA score did not validate for semaglutide, suggesting drug-specific genetic effects. The study used real-world data rather than controlled trial data, which may introduce confounders. Only 12–18 month outcomes were assessed.
How to read the evidence
This is a well-powered pharmacogenomic study with a large discovery cohort and independent validation, using real-world clinical data. While observational rather than randomized, the validation step strengthens confidence in the findings.
When this study was published
Published in 2025, this is cutting-edge pharmacogenomics research addressing one of the most timely questions in obesity medicine — predicting GLP-1RA response.
The bigger picture
Pharmacogenomics — using genetics to predict drug response — is becoming increasingly important as expensive new medications enter the market. This NBEA finding adds to the growing understanding that GLP-1RA efficacy has a genetic component, moving the field toward personalized obesity treatment where genetic testing could guide medication selection.
Questions still open
- Could NBEA genetic testing be integrated into clinical practice to guide GLP-1RA prescribing?
- Why does the NBEA non-response score validate for liraglutide but not semaglutide?
- Are there other genes that, combined with NBEA, could create a more comprehensive response prediction panel?
Common questions
Can a genetic test tell me if Ozempic or similar drugs will work for me?
Why don't GLP-1 receptor agonists work the same for everyone?
Read the original research
Neurobeachin (NBEA) is a novel gene associated with GLP-1 receptor agonist associated weight loss.
Diabetes, obesity & metabolism, 27(10), 5632-5642
Citation
Mariam-Smith, Arshiya; Breeyear, Joseph H; Daniels, Noah J; Pantalone, Kevin M; Griebeler, Marcio L; Motsinger-Reif, Alison A; Rotroff, Daniel M. (2025). Neurobeachin (NBEA) is a novel gene associated with GLP-1 receptor agonist associated weight loss.. Diabetes, obesity & metabolism, 27(10), 5632-5642. https://doi.org/10.1111/dom.16612