Ozempic's brain impact linked to heart benefits in study

Brain signals in patients taking weight-loss drugs such as Novo Nordisk's Ozempic may contribute to lowering heart disease and deaths, researchers said. 

Ozempic, Novo's Wegovy and Eli Lilly's Zepbound work in part by mimicking GLP-1, a hormone that moderates appetite and fights obesity, a known risk factor for heart disease. The drugs also activate anti-inflammatory pathways in the brain with far-reaching effects that may independently keep the heart healthy, according to a study.

"We have long thought the anti-inflammatory actions of GLP-1 were important, but the question was, how does that work?" Daniel Drucker, the study's lead author and a co-discoverer of the GLP-1 hormone, said in an interview. "This is now telling us that the anti-inflammatory actions of GLP-1 are likely in part organized through a subset of brain neurons." 

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GLP-1 drugs are carving out a huge market for diabetes and obesity that Goldman Sachs estimates will reach $100 billion by 2030. The brain findings published Monday in the journal Cell Metabolism underline the drugs' potential for treating a variety of other disorders, from heart and kidney disease to degenerative ailments like potentially Alzheimer's and Parkinson's disease. 

The new drugs activate GLP-1 receptors that are found on cells throughout the body, but concentrated in the pancreas and brain. Scientists have long known the drugs have some anti-inflammatory effects independent of their ability to cause weight loss, but how exactly this worked was largely a mystery. 

An older GLP-1 drug from GSK called Tanzeum, for example, didn't help people lose weight and was discontinued due to disappointing sales. But the company continued studying the drug and found it reduced heart attacks and strokes in patients with type 2 diabetes and a history of cardiovascular disease.

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More evidence of the phenomenon comes from a recent study showing that Wegovy cut the risk of heart attacks and strokes, even when patients lost little weight, said Drucker, a University of Toronto professor. Some markers of inflammation, such as a liver product called C-reactive protein, fell after patients started taking the drugs, according to the study from Novo Nordisk that was released at a November conference.

Inflammation is a known contributor to many diseases like obesity and diabetes, but the latest findings may hold promise for treating other metabolic conditions, Drucker said. He and his team have been working on the study, funded by the Canadian Institutes for Health Research and Novo Nordisk, for the past three years. 

The findings open up the opportunity "for yet another potential repurposing of existing GLP-1-based therapeutics for the treatment of disease," Matthew Hayes, a neuroscientist at the University of Pennsylvania, said in an email. Additional targets might include chronic inflammation and pain, he said. 

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Drucker's team, led by postdoctoral scientist Chi Kin Wong, induced inflammation and sepsis — a severe reaction to infection — in mice and treated them with Wegovy and Zepbound. The drugs reduced inflammation all over the animals' bodies, but only when GLP-1 receptors in the brain remained unblocked. 

Surprisingly, Lilly's Zepbound continued to have anti-inflammatory effects even when the researchers blocked receptors for the hormone in the brain, Drucker said. That suggests Zepbound, which mimics GLP-1 and another gut hormone called GIP, might have additional benefits, he said.