Association of <scp>SGLT2</scp> Inhibitor With Stroke in Type 2 Diabetes With Diabetic Retinopathy: A Multicenter Electronic Health Record Data Study

AIMS: Diabetic retinopathy (DR) is linked to elevated risks of cerebrovascular diseases. Whether sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce stroke risk in patients with type 2 diabetes (T2D) and DR remains uncertain. MATERIALS AND METHODS: We conducted a retrospective cohort study using the TriNetX Research Network. Adults with T2D and DR initiating SGLT2i versus dipeptidyl peptidase-4 inhibitors/metformin were identified. After 1:1 propensity score matching, ischemic stroke (IS) and hemorrhagic stroke (HS) risks at 1, 3 and 5 years were assessed using Cox models, with hazard ratios (HRs) and number needed to treat (NNT) estimated. RESULTS: After matching, 13 778 per group were included. SGLT2i use was associated with reduced HS risk at 1 year (HR: 0.76; 95% CI, 0.56-0.93), 3 years (HR: 0.79; 95% CI, 0.59-0.90), and 5 years (HR: 0.73; 95% CI, 0.60-0.89; NNT 100). IS risk reduction emerged at 5 years (HR: 0.92; 95% CI, 0.85-0.99; NNT 34). For patients with early-stage DR and HbA1c > 7%, HS risk decreased at 1 year (HR: 0.57; 95% CI, 0.37-0.89), 3 years (HR: 0.61; 95% CI, 0.41-0.83), and 5 years (HR: 0.64; 95% CI, 0.44-0.84). Sensitivity analyses showed consistent 5-year reductions in HS risk among patients with neuropathy, nephropathy and chronic kidney disease, with NNTs of 91, 59 and 84, respectively. CONCLUSIONS: SGLT2i was associated with lower stroke risk, particularly HS, in patients with T2D and DR. These findings suggest a potential cerebrovascular benefit, although prospective studies are needed to confirm this association.