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.

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

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).

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.