Cardiovascular Outcomes With Antidiabetic Drugs in People With Type 2 Diabetes and a Prior Stroke

To assess the comparative effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2i), thiazolidinediones (TZD), and dipeptidyl peptidase-4 inhibitors (DPP-4i) for the cardiorenal outcomes and mortality in individuals with type 2 diabetes and a prior stroke.

Using the Korean National Health Insurance Service database from 2014 to 2021, a new-user cohort was established through propensity score matching for SGLT2i, TZD, and DPP-4i. The primary outcomes were major adverse cardiovascular events (MACE), comprising myocardial infarction, ischemic stroke, and cardiovascular death. Secondary outcomes included individual components of MACE, hospitalization for heart failure, a composite kidney outcome, and all-cause mortality. Weighted Cox proportional hazard models were used to calculate HRs and 95% CIs.

Among 9733 participants (mean age, 67.2±3.2 years; 46.8% women), the incidence rate of MACE was 220, 202, and 251 per 1000 person-years for the SGLT2i, TZD, and DPP-4i groups. SGLT2i (HR, 0.86; 95% CI, 0.77 to 0.97; P=.01) and TZD (HR, 0.80; 95% CI, 0.70 to 0.90; P<.001) showed a lower risk of MACE compared to DPP-4i. Importantly, no significant difference in MACE was observed between SGLT2i and TZD. TZD was associated with a reduced risk of ischemic stroke, cardiovascular death, and the composite kidney outcome, whereas SGLT2i reduced risks of hospitalization for heart failure, the composite kidney outcome, and all-cause mortality compared to DPP-4i.

SGLT2i and TZD use in people with type 2 diabetes and a prior stroke was associated with reduced risks of MACE, the composite kidney outcome, and mortality compared with DPP-4i, with variations in effects on individual outcomes.