Can vascular dementia be treated with GLP-1s? Despite the failure of one trial, several researchers are optimistic.
Although there is rarely positive news regarding Alzheimer’s disease, a failed study could lead to additional research on vascular dementia.
On Monday, Novo Nordisk (NVO) revealed that Rybelsus, an oral GLP-1, was no more effective than a placebo at slowing the progression of Alzheimer’s disease. Other than stating that the semaglutide tablet had failed the closely watched Phase 3 research, it provided very little information.
Novo conducted two trials: evoke+, which was anticipated to enroll roughly 20% of patients with vascular dementia, Alzheimer’s, and mixed dementia (a condition in which a patient has been diagnosed with more than one type of dementia), and evoke, which evaluated Rybelsus in patients with early Alzheimer’s disease.
This is when things start to get interesting. According to Novo, the medication showed an improvement in biomarkers linked to Alzheimer’s disease, and the evoke+ trial seems to have under-enrolled patients with vascular dementia.
Because of this, some dementia specialists think there might still be a chance to create better trials that test medications like GLP-1s in individuals who have this type of dementia. (However, the trial’s complete data, which will be given at a medical conference on December 3, is what they want to see first.)
Dr. Sudha Seshadri, founding director of the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases at UT Health San Antonio, stated that there is now “recognition that vascular factors play a very important role, and the need for trials targeting vascular is going to remain.”
After Alzheimer’s, vascular dementia is the second most prevalent type of dementia. It is estimated that 2.7 million Americans suffer from vascular dementia, also known as mixed dementia, which is brought on by strokes or mini-strokes that harm the brain’s blood arteries.
For some patient populations, a mixed dementia diagnosis might better capture the impact of dementia. For instance, in South Texas, individuals with obesity, diabetes, and high blood pressure frequently have dementia and Alzheimer’s, according to Seshadri, who pointed out that these chronic illnesses all “cause not just atherosclerosis, but stiffening of the arteries.”
In addition to their dementia, many patients still require treatment for those diseases. However, compared to Alzheimer’s patients, those with vascular dementia have received significantly less investigation.
This is primarily due to Alzheimer’s-related biomarkers, such as amyloid plaques and neurofibrillary tangles, as well as genes, such APOE4, that are used to create novel medicines or determine which patients should receive them, such as Eisai’s (JP:4523) Leqembi and Eli Lilly’s (LLY) Kisunla or Biogen (BIIB). Vascular dementia does not have such goals.
It wasn’t until 2011 that the American Heart Association and American Stroke Association said that dementia and cognitive impairment can result from changes in vascular health.
According to Laura Nisenbaum, executive director of drug development for the Alzheimer’s Drug Discovery Foundation, “vascular dementia is not as well understood in the sense that we do know that it often results from damage to blood vessels in the brain, such as from stroke or also contributed from high blood pressure or diabetes,” but “we don’t have established biomarkers that we can use to stage the development.”
However, an increasing amount of empirical data indicates that the millions of people who have taken GLP-1s may be benefiting from neuroprotective and cerebrovascular effects, as Novo’s Wegovy and Lilly’s Zepbound have become increasingly popular.
“We can now look at how – in those individuals – there has been a reduced risk of developing dementia,” Nisenbaum said.
In addition to lowering the risk of stroke, heart attack, and mortality, Novo’s Wegovy is already approved for individuals who are overweight or obese. Additionally, the FDA approved the prescription of Rybelsus to patients with Type 2 diabetes last month in an effort to lower their risk of serious cardiovascular events. (Semaglutide is the active ingredient in both Wegovy and Rybelsus, although Wegovy is an injection and Rybelsus is a tablet.)
Data even suggests that vaccination against shingles may reduce the incidence of vascular dementia.
