Exploring the neuroprotective role of GLP-1 agonists against Alzheimer's disease: Real-world evidence from a propensity-matched cohort
Open accessAbstract
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.
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GLP-1 signalling affects several body systems, including gastrointestinal, cardiovascular, renal, and neuroendocrine pathways.
“Research indicates that GLP‐1 signalling affects several body systems, including gastrointestinal, cardiovascular, renal, and neuroendocrine pathways.”
From Comparative Efficacy and Safety of Glucagon Receptor Agonists on Metabolic Outcomes: A Network Meta‐Analysis of Randomised Controlled Trials (2026) · cites this paper as [37]
The Introduction (page unavailable) describes cardiovascular and renal benefits of GLP-1 receptor agonists, alongside glycemic and weight-related effects, and discusses possible effects on Alzheimer’s disease pathways. It does not describe gastrointestinal or neuroendocrine pathways, so it supports only part of the claimed list. (LLM, conf=0.85)
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- Authors
- AbuAlrob, M. A., Itbaisha, A., Abujwaid, Y. K., Abulehia, A., Hussein, A., & Mesraoua, B.
- Affiliations
- Hamad Medical Corporation (QA)
- Al-Quds University (PS)
- Virtua Health (US)
- Weill Cornell Medical College in Qatar (QA)
- Corresponding author
- AbuAlrob, Majd A
- ORCID
- Venue
- Journal of Alzheimer's Disease Reports
- Publisher
- SAGE Publications
- Published
- 2025-01
- Volume
- 9
- Pages
- 25424823251388650-25424823251388650
- ISSN
- 2542-4823 (ISSN-L)
- PMC
- PMC12536097
- OpenAlex
- W4415260874
- Cited by
- 10
- References
- 16
- Citations by year
- 2026: 10
- FWCI
- 6.43
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- Locations
- Journal of Alzheimer s Disease Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- Alzheimer's disease, dementia, GLP-1 receptor agonists, neuroprotection, liraglutide, semaglutide, dulaglutide, exenatide, albiglutide, incident dementia risk, amyloid burden, neuroinflammation, real-world evidence
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