Ozempic may protect against Alzheimer's

Over a decade ago, a smattering of studies suggested that early cousins of drugs like Ozempic and Mounjaro could prevent, or even reverse, signs of Alzheimer's disease in mice. Now, as the next generation of these medications has soared in popularity, and scientists discover they may have wide-ranging health benefits, research is revving up to investigate whether the drugs that upended diabetes and obesity care could also revolutionize Alzheimer's treatment.

Emerging evidence seems encouraging -- but questions and caveats abound.

"I think they're definitely promising," said Karolina Skibicka, a neuroscientist and the chair in metabolic physiology at Pennsylvania State University. "And that's sort of how far I would go with the currently available evidence."

The Early findings

Research in rodents has largely shown that these types of diabetes and obesity drugs, which mimic metabolic hormones, can improve several hallmarks of Alzheimer's disease in the brain, as well as boost the animals' ability to learn and remember. However, there is a long history of all sorts of drugs treating Alzheimer's in mice but not providing the same benefits for humans.

There are only a few studies so far examining whether these medications can reduce the risk for dementia in people.

One recent analysis found that, over the course of three years, people taking semaglutide (the compound in Ozempic and the weight loss drug Wegovy) were about 40% to 70% less likely to be diagnosed with Alzheimer's disease compared with people on other diabetes medications.

A paper published last month reviewing a Veterans Affairs database similarly found that people prescribed these drugs were less likely to develop dementia compared with those who took other diabetes drugs. The benefit was more modest, though, with a roughly 10% decreased risk.

The findings seem promising. But because these studies are observational, "it's really hard to tell" whether the drugs are directly causing that benefit, or whether that lower risk is more of a coincidence, said Dr. Ziyad Al-Aly, the chief of research and development at the Veterans Affairs St. Louis Healthcare System and an author on the study.

There are also clinical trials testing whether the drugs can treat people already diagnosed with dementia. Preliminary findings from one study of about 200 patients were presented at an Alzheimer's Association meeting last summer. They showed that patients with mild Alzheimer's disease who received an older, similar medication (liraglutide, sold under the brand name Victoza), had slower declines in both their cognition and brain volume compared with patients who received a placebo.

The benefits were modest, and the researchers couldn't say whether they would meaningfully change a patient's condition. But Dr. Paul Edison, a professor of neuroscience at Imperial College London who led the trial, said that he was "encouraged" by the results.

Other trials testing whether semaglutide can delay the progression of Alzheimer's disease are ongoing.

How the drugs might work

Researchers don't know how drugs like Ozempic might protect against neurodegenerative diseases -- in fact, they're still trying to understand how these drugs impact the brain overall. But they have a couple theories:

-- They improve metabolic health.

Diabetes and obesity both increase a person's odds of developing dementia, so it's possible that the drugs reduce that risk by improving metabolic health.

The two conditions are associated with increased inflammation in the body, and many scientists think that reducing inflammation is at least partly how the drugs improve other health conditions, including heart and kidney disease. The same dynamic may be happening in the brain: Inflammation can kill cells and contribute to neurodegenerative disease, and these drugs may help by reducing it.

There is some evidence from animal studies that the drugs can suppress brain inflammation, Skibicka said. But, she added, scientists can't directly link that to the improvements in Alzheimer's disease.

The medications can also curb insulin resistance, a hallmark of diabetes. Healthy insulin functioning is important for memory formation, and insulin resistance has been linked to Alzheimer's disease. Research in animals suggests that because these drugs may improve insulin signaling in the brain, they could protect against neurodegeneration, said Nigel Greig, a senior investigator at the National Institutes of Health who has studied these drugs for neurodegenerative disorders.

-- They may benefit the brain itself.

Scientists know that these medications target certain receptors in the brain, particularly in areas that are important for hunger and metabolism. Whether they can also meaningfully act on regions involved in learning and memory is an open question.

Research has found that an older and less common drug, exenatide (sold under the brand name Byetta), can access deeper parts of the brain, Skibicka said. That includes the hippocampus, an area that is damaged early on in Alzheimer's disease. The data for other medications, including semaglutide and liraglutide, are more mixed. Some experts think that the molecules in those drugs have difficulty passing through the blood-brain barrier, preventing them from penetrating effectively. Researchers are hopeful that drugs currently under development could better access those deeper brain structures.

Finally, a few studies in mice have found that the medications can reduce the buildup of the protein tau in the brain, which is a key contributor to Alzheimer's disease. Scaling back tau buildup could potentially help stave off cognitive decline in humans, Greig said, although a variety of medications have tried to target tau and had mixed results.

In all likelihood, the drugs' potential benefits would stem from not just one factor, but a combination of many. "The drug is not only working on the insulin resistance," Edison said. "It's clearly working on the other mechanisms. We know that for sure."

And regardless of how they work, if weight loss and diabetes drugs can be repurposed to prevent or treat dementia, experts will call that a win.

"The landscape of therapeutics for Alzheimer's disease is very, very thin," Al-Aly said. "There's not a whole lot of things that work, so any addition to this repertoire would be certainly welcome."