Comparative risk of dementia in diabetic stroke patients prescribed SGLT2 vs. DPP-4 inhibitors: A propensity-matched retrospective cohort study

Abstract

Objective: Diabetes is a significant risk factor for both stroke and dementia. This study aimed to compare the risk of incident dementia between sodium-glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors in diabetic patients with a history of ischemic stroke.

Materials: We conducted a propensity-matched retrospective cohort study using observational data from the TriNetX global federated health research network. Patients aged 18 years or older with type 2 diabetes (T2D) and a history of ischemic stroke, newly prescribed either an SGLT2 or DPP-4 inhibitor from July 1, 2013, to June 30, 2024, were included. Propensity score matching was employed to balance baseline characteristics between treatment groups. The primary outcome was incident dementia, with secondary outcomes including degenerative and vascular dementia.

Results: After propensity score matching, each group consisted of 15901 patients. Over a mean follow-up of 2.52 years, SGLT2 inhibitor use was associated with lower risks of overall dementia (hazard ratio [HR] 0.66; 95% confidence interval [CI] 0.59-0.74), degenerative dementia (HR 0.68; 95% CI 0.60-0.76), and vascular dementia (HR 0.59, 95% CI 0.49-0.70) compared to DPP-4 inhibitor use. These findings remained consistent across various sensitivity and subgroup analyses.

Conclusions: In diabetic patients with a history of ischemic stroke, initiating SGLT2 inhibitors, compared to DPP-4 inhibitors, is associated with a lower risk of incident dementia. This association was observed for both degenerative and vascular dementias. These findings support the preferential use of SGLT2 inhibitors in this high-risk population, warranting further investigation through randomized clinical trials.

Keywords: Dementia; Dipeptidyl peptidase-4 inhibitors; Risk; Sodium-glucose cotransporter 2 inhibitors; Stroke.