Exploring the neuroprotective role of GLP-1 agonists against Alzheimer's disease: Real-world evidence from a propensity-matched cohort.

Background: Alzheimer's disease (AD) is a leading cause of dementia with societal and economic burdens. While recent therapies offer disease-modifying potential, concerns remain about efficacy and safety. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), used in type 2 diabetes, show neuroprotective effects via reduced neuroinflammation and amyloid burden. Objective: To evaluate whether GLP-1RA use is associated with a reduced risk of incident dementia in adults aged ≥50 years using real-world data. Methods: We conducted a retrospective cohort study using the TriNetX platform, analyzing records from 142 healthcare organizations. Adults aged ≥50 were included, comparing GLP-1RA users (liraglutide, semaglutide, dulaglutide, exenatide, albiglutide) to non-users. Propensity-score matching balanced demographics and comorbidities. Incident dementia, defined by ICD-10 codes, was analyzed with Cox proportional-hazards models. Results: Matched cohorts (n = 147,505 each) had similar baseline characteristics. Dementia incidence was lower in GLP-1RA users (0.20% versus 0.44%), with a hazard ratio of 0.30 (95% CI 0.28-0.33; p < 0.001). Conclusions: GLP-1RA use was associated with a 70% reduced dementia risk, warranting further clinical evaluation.