Semaglutide side effects solved? Scientists target nerve cells responsible for nausea-free weight loss

Swedish researchers at the Sahlgrenska Academy of the University of Gothenburg have uncovered a specific group of nerve cells in the brain stem that appears to control how the anti-diabetic medication semaglutide affects appetite and weight — without causing nausea.

Specifically, they demonstrate that it is possible to distinguish the nerve cells in the brain that control beneficial effects — such as reduced food intake and fat loss — from those that contribute to side effects.

Semaglutide is an increasingly popular GLP-1 drug used to treat type 2 diabetes and obesity that reduces food intake and body weight. However, it is known to cause side effects such as nausea and muscle loss.

“Semaglutide and other GLP-1 receptor agonists are currently being prescribed to more and more people and are also being investigated for other potential indications such as substance use disorders and neurodegenerative diseases,” says Linda Engström Ruud, project researcher.

“It is important to understand how these drugs actually work. The better we understand this, the greater the opportunity we have to improve them.”

Activating nerve cells

To investigate how semaglutide affects the brain, the researchers worked with mice. After tracking which nerve cells were activated by the drug, they were able to stimulate these cells without administering the drug itself.

The result was that the mice ate less and lost weight, just as when treated with semaglutide. When these nerve cells were killed, the drug’s effect on appetite and fat loss decreased significantly instead. However, side effects such as nausea and muscle loss remained.

“This suggests that these nerve cells control the beneficial effects of semaglutide,” highlights Júlia Teixidor-Deulofeu, first author of the study and Ph.D. student at Sahlgrenska Academy.

“We have therefore identified a specific group of nerve cells that is necessary for the effects that semaglutide has on weight and appetite, but which does not appear to contribute to any significant extent to side effects such as nausea.”

“If we can target the treatment there, we may be able to maintain the positive effects while reducing side effects.”

Early step for improved treatment

The identified nerve cells are located in an area of the brain called the dorsal vagal complex.

This discovery is an early step toward potentially improved treatment and offers new knowledge about how semaglutide works in the brain, note the study authors. The paper, published in the journal Cell Metabolism, also provides deeper insight into how the brainstem regulates energy balance.

GLP-1 is a buzzword in pharmaceuticals, supplements and, more recently, in functional food and beverages. In April, Nutrition Insight hosted a webinar exploring the forefront of GLP-1-related nutrition innovations with Rousselot.