Daijiworld Media Network - San Diego

San Diego, Nov 22: Millions of Americans have successfully lost weight using drugs like Wegovy and Zepbound, but unpleasant side effects—especially nausea and vomiting—often force patients to stop treatment.

At this year’s Society for Neuroscience meeting, researchers discussed efforts to understand and minimize these side effects while preserving the drugs’ weight-loss benefits. GLP-1 agonists mimic a hormone that reduces appetite and slows digestion, but their effect on the brain can trigger nausea.

Warren Yacawych of the University of Michigan explained that the drugs affect two brain stem areas: one controlling nausea, known as the “vomit center,” and another monitoring fullness. Attempts to target only the fullness center prevented nausea in mice, but also blocked weight loss, highlighting the challenge of separating side effects from intended effects.

A potential solution emerged from Ernie Blevins’ team at the University of Washington, which combined low-dose GLP-1 with oxytocin in obese rats. This allowed the rats to lose weight without feeling sick.

GLP-1 drugs also reduce thirst, which could be dangerous for patients losing fluids due to side effects. Derek Daniels from the University at Buffalo studied “Brattleboro rats,” which are genetically very thirsty, to identify brain areas where GLP-1 affects thirst without impacting appetite. This could guide safer drug design in the future.

Researchers from the University of Virginia found that GLP-1 also acts on brain regions linked to reward and addiction. In mice, this reduced desire for high-reward foods while leaving healthy eating unchanged, suggesting potential applications in treating alcoholism and other substance use disorders.

The findings mark steps toward designing GLP-1 drugs that maximize weight loss and health benefits while minimizing nausea, dehydration, and other adverse effects.