Adults with type 2 diabetes mellitus (T2DM) and diabetic retinopathy (DR) have an elevated risk of cerebrovascular events, yet stroke outcomes with different glucose-lowering therapies remain incompletely defined. A retrospective cohort analysis published in Diabetes, Obesity and Metabolism evaluated stroke risk after initiation of sodium-glucose cotransporter-2 inhibitors (SGLT2i) compared with dipeptidyl peptidase-4 inhibitors or metformin in this high-risk population.

The study used data from the TriNetX Research Network and identified adults with T2DM and DR who started either treatment strategy. After 1:1 propensity score matching, 13,778 individuals were included in each group. Cox proportional hazards models were used to estimate risks of ischemic stroke (IS) and hemorrhagic stroke (HS) at 1, 3, and 5 years. Hazard ratios (HRs) with 95% confidence intervals (CIs) and number needed to treat (NNT) values were calculated.

Compared with the comparator group, SGLT2i use was associated with lower 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), with an NNT of 100 at 5 years. A lower IS risk was observed only at 5 years (HR 0.92, 95% CI 0.85-0.99), with an NNT of 34.

Among individuals with early-stage DR and glycated hemoglobin (HbA1c) above 7%, HS risk was lower 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 also demonstrated consistent 5-year reductions in HS risk among those with neuropathy, nephropathy, and chronic kidney disease (CKD), with NNT values of 91, 59, and 84, respectively.

These findings indicate that SGLT2i use was associated with lower long-term stroke risk, particularly hemorrhagic stroke, in adults with T2DM and DR, while prospective studies are needed to confirm these observations.