A recent study has provided real-world evidence suggesting the potential repurposing of glucagon-like peptide-1 receptor agonists (GLP-1 RAs), typically used to manage type 2 diabetes and obesity, for the prevention of Alzheimer’s disease (AD). Among the GLP-1 RAs evaluated, semaglutide was associated with a notably lower risk of AD compared to other antidiabetic medications. The findings have been published online on October 24 in Alzheimer’s & Dementia by a research team led by Dr. Rong Xu from Case Western Reserve School of Medicine, Cleveland, Ohio.
The analysis used electronic health records to compare outcomes between 17,104 new users of semaglutide and 1,077,657 users of other antidiabetic drugs, including various GLP-1 receptor-targeting medications, insulin, metformin, sulfonylureas, dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium-glucose cotransporter 2 (SGLT-2) inhibitors, and thiazolidinediones. Over a follow-up period of three years, semaglutide treatment was linked to a significantly reduced risk of Alzheimer’s disease.
The reduction in AD risk was most pronounced when compared to insulin (hazard ratio [HR], 0.33) and least significant when compared with other GLP-1 RAs (HR, 0.59). Overall, semaglutide use was associated with a 40-70% reduction in the risk of first-time Alzheimer’s diagnosis. These benefits were observed consistently across different age groups, gender, and obesity status.
Neuroprotective Effects of Semaglutide
Semaglutide has previously demonstrated neuroprotective effects in preclinical models of neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease. In animal studies, semaglutide was found to reduce beta-amyloid deposition and improve glucose metabolism in the brain, along with enhancing spatial learning and memory.
The study’s findings align with existing clinical evidence suggesting that GLP-1 RAs may provide cognitive protection. In a phase 2b trial called ELAD, liraglutide, another GLP-1 RA, was associated with slower cognitive decline and less brain atrophy over 12 months in adults with early-stage AD, compared to placebo.
Expert Opinions and Future Directions
According to Dr. Courtney Kloske, director of scientific engagement at the Alzheimer’s Association, diabetes is a recognized risk factor for Alzheimer’s disease. She explained that managing diabetes with drugs like semaglutide could benefit brain health not only by controlling blood glucose levels but also by potentially addressing pathways involved in cognitive decline.
Dr. Kloske noted that the Alzheimer’s Association’s “Part the Cloud” initiative has invested more than $68 million in over 65 clinical trials investigating new and repurposed drugs aimed at treating Alzheimer’s through various mechanisms. Although the results regarding semaglutide are promising, further clinical trials are needed to confirm its efficacy in preventing or delaying the onset of Alzheimer’s disease.
With semaglutide already approved for type 2 diabetes and weight management, its potential for Alzheimer’s prevention represents a promising but preliminary step toward expanding the therapeutic applications of GLP-1 receptor agonists.
References:
1. https://pubmed.ncbi.nlm.nih.gov/39445596/
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