BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with an elevated risk of dementia, including Alzheimer's disease (AD) and vascular dementia (VaD). While sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists have shown neuroprotective potential, comparative data on their efficacy in dementia prevention remain scarce.
METHODS: - We conducted a retrospective cohort study using the TriNetX database, including 307,103 SGLT2 inhibitor users and 348,686 GLP-1 receptor agonist users with T2DM. Propensity score matching yielded 221,883 pairs with balanced baseline characteristics. The primary outcome was overall dementia incidence, with secondary outcomes including AD, VaD, and all-cause mortality. Hazard ratios (HRs) were calculated using Cox proportional hazards models.
RESULTS: SGLT2 inhibitors were associated with a significantly lower incidence of overall dementia compared to GLP-1 receptor agonists (2.7 % vs. 3.6 %; HR, 0.92; 95 % CI, 0.89-0.95). The risk of VaD (HR, 0.89; 95 % CI, 0.84-0.95) and AD (HR, 0.90; 95 % CI, 0.86-0.94) was also reduced with SGLT2 inhibitors. All-cause mortality was lower in the SGLT2 group (3.6 % vs. 4.6 %; HR, 0.95; 95 % CI, 0.92-0.98). No significant difference was observed in other dementia subtypes (HR, 0.96; 95 % CI, 0.91-1.01).
CONCLUSIONS: In this large, real-world cohort, SGLT2 inhibitors demonstrated superior efficacy over GLP-1 receptor agonists in reducing the risks of overall dementia, VaD, and AD among patients with T2DM. These findings support the preferential use of SGLT2 inhibitors in mitigating dementia risk in this population, though randomized controlled trials are warranted for confirmation.
