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What’s the mechanism behind behavioral side effects of popular weight loss drugs?

2025-01-22
(Press-News.org) Glucagon-like peptide 1 receptor agonists (GLP1RA)—medications for type 2 diabetes and obesity that have recently been making headlines due to a rise in popularity as weight loss agents—have been linked with behavioral side effects. A large population-based analysis in Diabetes, Obesity and Metabolism assessed whether certain genetic variants might help explain these effects.

GLP1RA mimic the GLP-1 hormone in the body that helps control insulin and blood glucose levels and promotes feelings of satiety. GLP-1 binds to GLP1R on cells in the brain and pancreas.

For the analysis, investigators examined common genetic variants in the GLP1R gene in 408,774 white British, 50,314 white European, 7,667 South Asian, 10,437 multiple ancestry, and 7,641 African-Caribbean individuals.

Variants in the GLP1R gene had consistent associations with cardiometabolic traits (body mass index, blood pressure, and type 2 diabetes) across ancestries. GLP1R variants were also linked with risk-taking behavior, mood instability, chronic pain, and anxiety in most ancestries, but the results were less consistent. The genetic variants influencing cardiometabolic traits were separate from those influencing behavioral changes and separate from those influencing expression levels of the GLP1R gene.

The findings suggest that any observed behavioral changes with GLP1RA are likely not acting directly through GLP1R.

“Whilst it is not possible to directly compare genetic findings to the effects of a drug, our results suggest that behavioral changes are unlikely to be a direct result of the GLPRAs. Exactly how these indirect effects are occurring is currently unclear,” said corresponding author Rona J. Strawbridge, PhD, of the University of Glasgow, in the UK.

URL upon publication: https://onlinelibrary.wiley.com/doi/10.1111/dom.16178

 

Additional Information
NOTE: The information contained in this release is protected by copyright. Please include journal attribution in all coverage. For more information or to obtain a PDF of any study, please contact: Sara Henning-Stout, newsroom@wiley.com.

About the Journal
Diabetes, Obesity and Metabolism is the only interdisciplinary journal for high-quality research and reviews in the areas of diabetes, obesity and metabolism. We focus on clinical and experimental pharmacology and therapeutics in any aspect of metabolic and endocrine disease, either in humans or animal and cellular systems. We also welcome manuscripts reporting on clinical data relating to novel devices, apps, glucose sensors and insulin pumps used to improve glycaemic control.

About Wiley      
Wiley is one of the world’s largest publishers and a trusted leader in research and learning. Our industry-leading content, services, platforms, and knowledge networks are tailored to meet the evolving needs of our customers and partners, including researchers, students, instructors, professionals, institutions, and corporations. We empower knowledge-seekers to transform today’s biggest obstacles into tomorrow’s brightest opportunities. For more than two centuries, Wiley has been delivering on its timeless mission to unlock human potential. Visit us at Wiley.com. Follow us on Facebook, X, LinkedIn and Instagram.

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[Press-News.org] What’s the mechanism behind behavioral side effects of popular weight loss drugs?