Drug-specific Effects of GLP-1 Receptor Agonists on Dementia Risk: A Network Meta-analysis
Arkansh Sharma1, Vinay Suresh2, Rishu Raj3, Aditi Agarwal4, Allimuthu Nithyanandam5, Muaz Ali6
1Government Medical College, Omandurar, Chennai, Tamil Nadu, India, 2University of Oxford, United Kingdom, 3Atal Bihari Vajpayee Institute of Medical Sciences and Dr. RML Hospital, New Delhi, India, 4Osmania Medical College, Hyderabad, India, 5Department of Neurology, Tamil Nadu Government Multi-Super Speciality Hospital, Omandurar Government Estate, Chennai, India, 6Cleveland Clinical Florida, USA
Objective:

To assess the effects of individual glucose-lowering drugs on the risk of all-cause dementia, with emphasis on drug-level distinctions within the GLP-1 receptor agonist class.


Background:

Most meta-analyses evaluate glucose-lowering therapies at the class level, potentially obscuring differences among individual agents with distinct pharmacology.


Design/Methods:
We systematically searched PubMed, EMBASE, SCOPUS, and Web of Science till September 2025 for randomized controlled trials reporting dementia outcomes with glucose-lowering therapies. A frequentist, random-effects, graph-theoretical network meta-analysis was conducted for individual GLP-1 receptor agonists. Language and reporting clarity were refined using ChatGPT (OpenAI, GPT-5).
Results:

Twenty-six RCTs including 164,531 participants were analyzed. Liraglutide 1.8 mg daily significantly reduced all-cause dementia risk versus placebo (OR 0.48; 95% CI 0.24–0.95). Other agents showed non-significant trends: albiglutide 30–50 mg weekly (OR 0.14; 95% CI 0.0074–2.77), efpeglenatide 2–6 mg weekly (OR 0.07; 95% CI 0.0031–1.39), lixisenatide 20 mcg daily (OR 0.33; 95% CI 0.014–8.18), semaglutide 0.5–1 mg weekly (OR 0.60; 95% CI 0.14–2.51), semaglutide 14 mg daily (OR 0.20; 95% CI 0.010–4.17), semaglutide 2.4 mg weekly (OR 0.75; 95% CI 0.17–3.35), dulaglutide 1.5 mg weekly (OR 0.78; 95% CI 0.29–2.09), and exenatide 2 mg weekly (OR 1.01; 95% CI 0.14–7.14).


Conclusions:

Liraglutide is associated with a significant reduction in all-cause dementia, while other GLP-1 receptor agonists showed non-significant trends. These findings highlight the importance of drug-level analyses and warrant further research into cognitive effects across agents.


10.1212/WNL.0000000000216715
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