Abstract Dementia, particularly Alzheimer’s disease (AD), is a major global health challenge with limited treatment options. Growing evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1 RAs), originally developed for type 2 diabetes mellitus (T2DM), may offer neuroprotective benefits by improving insulin signalling, reducing amyloid-beta accumulation, and lowering neuroinflammation. Following PRISMA guidelines, a systematic literature search (2015–2025) was conducted using PubMed and Google Scholar. Eligible studies included randomized controlled trials (RCTs), longitudinal cohort studies, and systematic reviews assessing GLP-1 RAs’ effects on cognitive outcomes. Studies focusing solely on metabolic markers or non-human models were excluded. Fifteen studies met the inclusion criteria. Clinical evidence suggests that Liraglutide and Semaglutide significantly slow cognitive decline and reduce dementia risk in T2DM patients compared to metformin and dipeptidyl peptidase-4 (DPP-4) inhibitors. Mechanistic studies highlight the role of GLP-1 RAs in enhancing insulin sensitivity, reducing oxidative stress, and modulating neuroinflammation. While GLP-1 RAs demonstrate promise in dementia prevention, further long-term RCTs are necessary to confirm their efficacy, establish optimal treatment protocols, and explore their use in non-diabetic populations. If validated, these findings could lead to a new class of neuroprotective therapies, transforming dementia prevention strategies.
Gupta et al. (Fri,) studied this question.
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