More Evidence Links Semaglutide to a Reduced Risk of Alzheimer’s

A new study provides real-world evidence supporting the potential repurposing of glucagon-like peptide 1 receptor agonists (GLP-1 RAs), used to treat type 2 diabetes and obesity, for the prevention of Alzheimer’s disease (AD).

Adults with type 2 diabetes who were prescribed the GLP-1 RA semaglutide had a significantly lower risk of AD compared with their peers who were prescribed one of seven other antidiabetic drugs, including other types of GLP-1 receptor-targeted drugs.

“These findings support further clinical trials to assess the potential of semaglutide in delaying or preventing AD,” write the researchers, led by Rong Xu, PhD, of Case Western Reserve School of Medicine, Cleveland, Ohio.

The research was published online on October 24 Alzheimer’s and dementia.

Real world data

Semaglutide has demonstrated neuroprotective effects in animal models of neurodegenerative diseases, including AD and Parkinson’s disease. In animal models of AD, the drug reduced beta-amyloid deposition and improved spatial learning and memory, as well as glucose metabolism in the brain.

In a real-world analysis, Xu and colleagues used data from electronic health records to identify 17,104 new users of semaglutide and 1,077,657 new users of seven other antidiabetic drugs, including other GLP-1 RAs, insulin, metformin, dipeptidyl peptidase 4 inhibitors, sodium-glucose cotransporter 2 inhibitors, sulfonylurea and thiazolidinedione.

Over three years, treatment with semaglutide was associated with a significantly reduced risk of developing AD, most strongly compared with insulin (hazard ratio (HR), 0.33) and weakest compared with other GLP-1 RAs (HR, 0.33). 59).

Compared with the other drugs, semaglutide was associated with a 40%-70% lower risk of first diagnosis of AD in patients with type 2 diabetes, with similar reductions observed across obesity status and gender and age groups, the authors reported.

The findings are consistent with recent evidence suggesting that GLP-1 RAs may protect cognitive function.

For example, as previously reported by Medscape Medical NewsIn the Phase 2b ELAD clinical trial, adults with early-stage AD taking the GLP-1 RA liraglutide showed slower declines in memory and thinking and experienced less brain atrophy over 12 months compared to placebo.

Promising, but tentative

Contacted for comment, Courtney Kloske, PhD, director of scientific engagement for the Alzheimer’s Association, noted that diabetes is a known risk factor for Alzheimer’s disease and that managing diabetes with medications like semaglutide “would benefit brain health can be achieved by simply controlling diabetes.”

“However, we still need large clinical trials in representative populations to determine whether semaglutide specifically reduces the risk of Alzheimer’s disease, so it is too early to recommend it for prevention,” Kloske told me. Medscape Medical News.

She noted that some research suggests that GLP-1 RAs “may help reduce inflammation and positively impact the brain’s energy use. However, more research is needed to fully understand how these processes may contribute to preventing cognitive decline or Alzheimer’s disease,” Kloske cautioned.

The Alzheimer’s Association’s “Part the Cloud” initiative has invested more than $68 million to advance 65 clinical trials targeting a variety of compounds, including repurposed drugs that can address known and potential new aspects of the disease, it said Kloske.

The study was supported by grants from the National Institute on Aging and the National Center for Advancing Translational Sciences. Xu and Kloske have no relevant conflicts.