MW There's still hope GLP-1 drugs could slow the second-biggest type of dementia

By Jaimy Lee

Even though Novo Nordisk's GLP-1 failed in Alzheimer's trial, some researchers are cautiously optimistic that obesity and diabetes drugs may have benefits for people with vascular dementia

Can GLP-1s treat vascular dementia? One study failed, but some researchers are holding out hope.

There's rarely good news about Alzheimer's disease, but a failed study may open the door to more research about vascular dementia.

Novo Nordisk (NVO) announced Monday that its oral GLP-1 called Rybelsus wasn't better than a placebo at delaying the progression of Alzheimer's disease. It shared few details beyond saying the semaglutide pill had failed the closely watched Phase 3 study.

Novo ran two trials: evoke, which assessed Rybelsus in patients with early Alzheimer's disease, and evoke+, which was expected to enroll about 20% of patients with vascular dementia as well as people with Alzheimer's and mixed dementia, which is when a patient is diagnosed with more than one type of dementia.

Here's where it gets interesting. The evoke+ trial appeared to have under-recruited patients with vascular dementia, and Novo said that the drug demonstrated an improvement in Alzheimer's-related biomarkers.

This is why some dementia experts believe there may still be an opportunity to design better trials that test drugs like GLP-1s in patients with this form of dementia. (That said, the first thing they want to see is the trial's full data, which is set to be presented Dec. 3 at a medical conference.)

There's now a "recognition that vascular factors play a very important role, and the need for trials targeting vascular is going to remain," said Dr. Sudha Seshadri, founding director of the Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases at UT Health San Antonio.

Vascular dementia is the second-most common form of dementia after Alzheimer's. About 2.7 million people in the U.S. are thought to have mixed dementia or vascular dementia, which is caused by strokes or mini-strokes that damage blood vessels in the brain.

A mixed dementia diagnosis may be a better reflection of how dementia affects certain patient populations. In South Texas, for example, Alzheimer's and dementia often co-exist in the patients who are managing obesity, diabetes and high blood pressure, according to Seshadri, who noted that the chronic conditions all "cause not just atherosclerosis, but stiffening of the arteries."

These patients still need to treat those conditions in addition to their dementia. But there's also been far less research into patients with vascular dementia than in Alzheimer's.

That's mostly because there are Alzheimer's-associated biomarkers like amyloid plaques and neurofibrillary tangles and genes such as APOE4 that are used to develop new therapies or assess who should get treatments, like Eli Lilly's $(LLY)$ Kisunla or Biogen $(BIIB)$ and Eisai's (JP:4523) Leqembi. There are no such targets for vascular dementia.

It wasn't until 2011 that the American Heart Association and American Stroke Association came out and said changes in vascular health can cause cognitive impairment and dementia.

"Vascular dementia is not as well understood in the sense that we do know that it is often resulting from damage to blood vessels in the brain, such as from stroke or also contributed from high blood pressure or diabetes," said Laura Nisenbaum, executive director of drug development for the Alzheimer's Drug Discovery Foundation, "but we don't have established biomarkers that we can use to stage the development."

Yet as Novo's Wegovy and Lilly's Zepbound have soared in popularity, there is a growing body of real-world research showing that the millions of people who have taken GLP-1s may be getting neuroprotective and cerebrovascular benefits.

"We can now look at how - in those individuals - there has been a reduced risk of developing dementia," Nisenbaum noted.

Novo's Wegovy is already approved for people with obesity or are overweight, in addition to helping those patients lower the risk of stroke, heart attack and death. And last month the FDA gave the OK for Rybelsus to be prescribed to Type 2 diabetes patients to reduce the risk of major cardiovascular events. (Wegovy and Rybelsus are both made with semaglutide, though Wegovy is an injection and Rybelsus is a pill.)

There's even data showing that getting a shingles vaccine can lower the risk of vascular dementia.

-Jaimy Lee

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November 24, 2025 16:57 ET (21:57 GMT)

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