A Philly lab reveals how obesity drugs like Ozempic cause nausea

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Researchers at the Monell Chemical Senses Center in Philadelphia have made a significant breakthrough in understanding the side effects of obesity drugs like Ozempic.

The study, led by neuroscientist Amber Alhadeff and her team, focused on semaglutide, the active ingredient in GLP-1 drugs such as Wegovy and Ozempic. Semaglutide is known to affect brain circuits, reducing feelings of hunger while also increasing feelings of nausea in many patients.

“We wanted to ask whether separate neurons and separate brain circuits mediate the weight loss effects versus the nausea and the side effects of these drugs,” said Alhadeff.  “And long story short, we were able to show that these two different brain regions each mediate one of these.

Alhadeff and her colleagues aimed to determine whether it is possible to suppress appetite without causing nausea, or if these two sensations are inseparably linked. Their research on mice revealed that by deactivating different brain circuits, the animals consumed less food without experiencing nausea.

“There’s always been a mystery about the relationship between being full and being nauseous,” Alhadeff said. “So we’ve always experienced this on kind of a continuum. The classic example is Thanksgiving dinner; we eat until we’re feeling a little too sick. Our results from the perspective of GLP-1 drugs were quite surprising. We actually didn’t expect necessarily up-front to be able to find a circuit that causes the fullness without causing the nausea and aversion, even when we drove the neurons really hard. So that was very exciting.”

Alhadeff said the discovery opens up new avenues for understanding brain function and could lead to the development of more tolerable weight loss medications in the future.