Association of SGLT2 Inhibitor With Stroke in Type 2 Diabetes With Diabetic Retinopathy: A Multicenter Electronic...

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.

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.

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.

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.