Media release

From: Wiley

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

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 Metabolismassessed 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.