Abstract Details

Title GLP-1 Receptor Agonists in Alzheimer’s Disease: A Living Systematic Review Integrating Clinical Trials, Real-world Evidence, and Translational Feasibility

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P3 - Poster Session 3 (5:00 PM-6:00 PM)

Poster/Presentation
Number 13-010

Objective To systematically evaluate the clinical efficacy, biomarker effects, and real-world dementia risk reduction associated with GLP-1 receptor agonists in Alzheimer’s disease, integrating trial and population data through a living systematic review and Efficacy–Feasibility Matrix to assess their translational readiness for scalable, disease-modifying intervention.

Background GLP-1 receptor agonists (GLP-1 RAs), developed for diabetes and obesity, cross the blood-brain barrier and modulate insulin signaling, neuroinflammation, and amyloid-tau pathways. Their dual metabolic and neuroprotective actions position them as leading repurposed candidates for Alzheimer’s disease (AD).

Design/Methods This living systematic review synthesized phase 2/3 trials and large real-world studies of liraglutide, semaglutide, and exenatide in MCI and AD (2000–2025). Data on cognition, biomarkers, safety, delivery, and accessibility were analyzed to compare efficacy with population-level dementia risk reduction. Translational readiness was mapped using an Efficacy–Feasibility Matrix.

Results Across > 2,000 participants, liraglutide (daily SC, 12 mo) slowed FDG-PET decline and hippocampal atrophy (standardized Δ ≈ 0.25 SD; p ≈ 0.04) despite a neutral primary outcome. Semaglutide (oral daily; EVOKE / EVOKE+) has the highest statistical power (N ≈ 1,800 each); results are expected in 2025. Exenatide (weekly SC) remained underpowered and neutral. Real-world diabetic cohorts (N > 2 million) consistently demonstrated ~20–35 % lower dementia incidence among GLP-1 users, strongest for semaglutide, compared with DPP-4 or SGLT2 users. Translational mapping positioned GLP-1 RAs as high-efficacy, moderate-feasibility interventions: biologically robust yet limited by cost and injectable delivery. Safety mirrored metabolic indications (GI symptoms > 10 %, no CNS toxicity).

Conclusions GLP-1 RAs currently represent the most mature, mechanistically coherent repurposed strategy for AD. Integrating trial and real-world evidence underscores consistent neuroprotective trends across settings. Pending phase 3 readouts will clarify disease-modifying potential. The Efficacy–Feasibility Matrix highlights semaglutide’s translational edge through oral dosing and scalability, supporting near-term pragmatic deployment if efficacy is confirmed.

Authors/Disclosures
Aditya Jain, MBBS PRESENTER	Dr. Jain has nothing to disclose.
Aditi Narsinghpura, MBBS	Dr. Narsinghpura has nothing to disclose.
Abhigna Mallepally, MBBS	Abhigna Mallepally, MBBS has nothing to disclose.
SANKRANTHI SARATH CHANDRA, MBBS	Dr. CHANDRA has nothing to disclose.
Salma Younas, PhD, PharmD	Miss Younas has nothing to disclose.
Sweta Sahu	Dr. Sahu has nothing to disclose.

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