MEDIA INQUIRIES
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As obesity continues to pose a major global health challenge, millions of people turn to GLP-1-based drugs, like Ozempic, for weight loss. But questions remain about who benefits most from these treatments. While prior research has examined demographic and lifestyle factors, the role of genetic variation in shaping individual responses has been largely unexplored.
In a new study published in Nature Medicine, researchers led by Jakob German, a PhD Fellow at the Eric and Wendy Schmidt Center, analyzed data from more than 10,000 individuals to investigate whether genetic risk influences how well people respond to two leading weight-loss interventions: GLP1-RAs and bariatric surgery. Working with collaborators from more than 40 institutions across six countries, the team combined genetic and clinical data from nine large-scale biobanks spanning Europe, North America, and the Middle East. By integrating clinical records and genomic profiles at this scale, they conducted one of the largest multi-ancestry studies to date examining how genetic differences affect responses to weight-loss treatments.
The researchers tested whether plausible genetic risk factors, including polygenic scores (PGS) for body mass index (BMI) and type 2 diabetes, could explain variability in weight loss after treatment. They found that genetic risk played little to no role in shaping weight loss for patients on GLP1-RA therapy. This suggests that GLP-1 therapies may offer consistent weight-loss benefits regardless of a person’s genetic predisposition to obesity or diabetes, making them a promising tool for equitable obesity care across diverse populations.
Bariatric surgery results revealed a similar story. While the PGS for BMI did reach statistical significance in some analyses, the effects were small — too minor to matter in a clinical setting. Together, these findings indicate that common genetic variation explains little of the variability in weight loss following surgery.
“Large-scale studies allow us to evaluate the real-world impact of genetics on treatment response,” said German. “Our results reinforce the idea that GLP1-RAs are broadly effective, independent of genetic background. It’s an encouraging finding for equitable and scalable obesity treatment.”
A key strength of the study was its integration of genomic and clinical data from diverse populations, underscoring the importance of scale in testing assumptions and guiding precision medicine. This approach aligns with the Schmidt Center’s mission to harness data and interdisciplinary science for transformative biomedical research.
The authors suggest future work could explore more targeted genetic predictors or examine individuals using GLP1-RAs specifically for obesity rather than type 2 diabetes. For now, their findings provide strong evidence that genetic risk alone should not limit access to GLP-1-based therapies and that these drugs may benefit many, regardless of inherited risk. Ultimately, studies like this help lay the foundation for more precise, data-driven approaches to understanding individual variation in response to GLP1-RAs and improving obesity care.
