Researchers at the University of Gothenburg have identified a group of nerve cells in the brainstem that appear to be responsible for the positive effects of semaglutide, such as appetite suppression and fat loss, without triggering side effects like nausea.

This breakthrough could lead to the development of more refined anti-obesity medications.

Semaglutide, a member of the GLP-1R agonists family, has gained popularity for managing obesity and type 2 diabetes. While effective, it can cause unwanted side effects, including muscle loss and nausea.

In a new study published in Cell Metabolism, scientists at Sahlgrenska Academy discovered that it’s possible to separate the neural pathways responsible for the drug’s therapeutic benefits from those involved in adverse reactions.

Using mice models, researchers identified which neurons were activated by semaglutide. When these neurons were stimulated, without giving the drug, mice showed reduced food intake and weight loss. When these same neurons were destroyed, semaglutide’s effects on appetite significantly weakened, yet side effects persisted.

“This strongly suggests that these particular neurons are essential for the weight-reducing and appetite-lowering properties of semaglutide” said Júlia Teixidor-Deulofeu, lead author and PhD student.

These neurons are located in the dorsal vagal complex, an area of the brainstem involved in regulating energy balance.
According to researcher Linda Engström Ruud, the findings not only open the door to more targeted obesity treatments but also expand our understanding of how GLP-1-based drugs interact with the brain’s neural circuits.