Could Weight Loss Drugs Also Prevent Alzheimer’s?

Over a decade ago, studies hinted that early relatives of drugs such as Ozempic and Mounjaro could prevent or even reverse Alzheimer’s symptoms in mice. As these newer medications gain popularity for their weight loss and diabetes benefits, researchers are investigating whether they could also transform Alzheimer’s treatment.

Emerging evidence is encouraging but comes with many unanswered questions.

“I think they’re definitely promising,” said Karolina Skibicka, a neuroscientist and chair in metabolic physiology at Pennsylvania State University. “But that’s how far I’d go with the current evidence.”

Early Findings

Research on rodents has consistently shown that these types of diabetes and obesity drugs, which mimic metabolic hormones, can improve Alzheimer’s markers in the brain, enhance learning, and boost memory. However, numerous drugs have succeeded in treating Alzheimer’s in mice but not in humans.

There are few studies examining whether these medications reduce dementia risk in people.

A recent analysis found that people taking semaglutide (the active ingredient in Ozempic and Wegovy) were 40 to 70 percent less likely to develop Alzheimer’s over three years compared to those on other diabetes medications.

Another study reviewed a Veterans Affairs database and found that these drugs reduced dementia risk by about 10 percent compared to other diabetes treatments.

While these findings are promising, the studies are observational, so it’s unclear if the drugs directly cause the benefits or if they are merely coincidental, said Dr. Ziyad Al-Aly, chief of research and development at the Veterans Affairs St. Louis Healthcare System.

Clinical trials also explore whether these drugs can treat existing dementia. Preliminary results from a trial of liraglutide (brand name Victoza) showed that patients with mild Alzheimer’s had slower cognitive decline and less brain shrinkage compared to those on a placebo.

While the benefits were modest, Dr. Paul Edison, a professor of neuroscience at Imperial College London, was encouraged by the results.

Additional trials investigating whether semaglutide can delay Alzheimer’s progression are ongoing.

How the Drugs Might Work

Researchers are unsure how these drugs protect against neurodegenerative diseases, but they have a few theories.

Improved Metabolic Health

Diabetes and obesity increase dementia risk, so these drugs might reduce that risk by improving metabolic health. Both conditions are linked to increased inflammation, which these drugs may mitigate.

Research in animals suggests that the drugs can reduce brain inflammation, but it’s not yet clear if this directly improves Alzheimer’s symptoms. They also improve insulin resistance, a hallmark of diabetes. Healthy insulin function is crucial for memory, and insulin resistance has been tied to Alzheimer’s.

Nigel Greig, a senior investigator at the National Institutes of Health, believes these drugs may protect against neurodegeneration by enhancing insulin signaling in the brain.

Direct Brain Benefits

These medications target certain receptors in the brain, particularly in areas involved in hunger and metabolism. Whether they also influence brain regions crucial for learning and memory is uncertain.

An older drug, exenatide (Byetta), can reach deeper brain regions, including the hippocampus, which is damaged early in Alzheimer’s. Data on semaglutide and liraglutide are more mixed, with some experts believing these drugs may have difficulty crossing the blood-brain barrier.

However, researchers are optimistic about new drugs being developed that could access these deeper brain structures.

A few studies in mice have shown these medications can reduce tau protein buildup, a key Alzheimer’s contributor. Reducing tau buildup might slow cognitive decline in humans, though many medications targeting tau have shown mixed results.

According to Dr. Edison, the drugs likely benefit Alzheimer’s patients through multiple mechanisms, not just insulin resistance.

Regardless of the precise mechanisms, repurposing weight loss and diabetes drugs for dementia could be a significant breakthrough.

“The landscape of therapeutics for Alzheimer’s disease is very thin,” Dr. Al-Aly said. “There’s not much that works, so any new additions would be welcome.”