Exploring the neuroprotective role of GLP-1 agonists against Alzheimer's disease: Real-world evidence from a propensity-matched cohort
<h3 dir="ltr">Background</h3><p dir="ltr">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-...
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2025
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| Summary: | <h3 dir="ltr">Background</h3><p dir="ltr">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.</p><h3 dir="ltr">Objective</h3><p dir="ltr">To evaluate whether GLP-1RA use is associated with a reduced risk of incident dementia in adults aged ≥50 years using real-world data.</p><h3 dir="ltr">Methods</h3><p dir="ltr">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.</p><h3 dir="ltr">Results</h3><p dir="ltr">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).</p><h3 dir="ltr">Conclusions</h3><p dir="ltr">GLP-1RA use was associated with a 70% reduced dementia risk, warranting further clinical evaluation.</p><h2 dir="ltr">Other Information</h2><p dir="ltr">Published in: Journal of Alzheimer's Disease Reports<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1177/25424823251388650" target="_blank">https://dx.doi.org/10.1177/25424823251388650</a></p> |
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