Effects of GLP-1 receptor agonists on vascular dementia: a systematic review and meta-analysis

Vascular dementia (VaD) is strongly associated with type 2 diabetes (T2DM), overweight, and obesity. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduce cardiovascular risk and exhibit neuroprotective properties, yet their effects in incident VaD remain uncertain. This study evaluated whether GLP-1 RAs have preventive potential for VaD in adults with T2DM, overweight, or obesity.

A systematic review and meta-analysis of randomized-controlled clinical trials (RCTs) was conducted to estimate the risk of incident VaD among patients with T2DM or overweight/obesity treated with GLP-1 RAs versus placebo. Data were pooled using a random-effects model, with outcomes expressed as risk ratios (RRs) and 95% confidence intervals (CIs). Subgroup analysis was performed after stratification by population type (T2DM vs. overweight/obesity), and meta-regression assessed the association between RCT duration and effect size.

Seven RCTs (six in T2DM, one in overweight/obesity) comprising 61,610 participants were included. GLP-1 RA treatment was not associated with a statistically significant difference in VaD incidence (RR: 0.50; 95% CI: 0.19-1.32; I² = 0%). Subgroup analysis revealed no significant between-group differences (p for subgroups = 0.612), although numerically lower VaD rates were observed in the T2DM subgroup (RR: 0.38; 95% CI: 0.13-1.11). Meta-regression did not demonstrate a significant association between follow-up duration and treatment effect (β = -0.291; SE = 0.212; 95% CI: -0.843 to 0.262; p = 0.229).

The pooled evidence did not confirm a statistically significant reduction in VaD risk with GLP-1 RA therapy. Numerically lower VaD incidence in T2DM populations warrants further investigation in adequately powered and systematically adjudicated trials.