Cardiovascular and renal benefits of dapagliflozin in patients with short and long‐standing type 2 diabetes: Analysis from the DECLARE‐TIMI 58 trial

Abstract

Aims We investigated whether the cardiovascular and renal benefits observed with dapagliflozin in the DECLARE‐TIMI 58 trial are observed also in patients with short‐ and long‐standing diabetes. Materials and Methods This post‐hoc analyses studied the dual primary efficacy endpoints, composite of cardiovascular death or hospitalization for heart failure (CVD/HHF) and major adverse cardiovascular events (MACE; CVD, myocardial infarction [MI], ischemic stroke), by diabetes duration. Results Of the 17 160 patients, 3836 had diabetes duration ≤5 years, 4731 > 5–10 years, 3952 > 10–15 years, 2433 > 15–20 years, and 2206 > 20 years. Dapagliflozin reduced the risk of CVD/HHF by a similar amount across diabetes duration subgroups, ranging from HR 0.79(0.58–1.06) in patients with duration ≤5 years to 0.75(0.55–1.03) in those >20 years (interaction‐trend‐p‐value 0.76). HR for MACE ranged from 1.08(0.87–1.35) in patients with diabetes duration ≤5 years to 0.67(0.52–0.86) in those >20 years (interaction‐trend‐p‐value 0.004). This was driven by greater reductions in risk of MI and ischemic stroke with dapagliflozin in patients with longer‐standing diabetes (interaction‐trend‐p‐values 0.019 and 0.015, respectively). The duration‐based MACE heterogeneity was apparent in those with or without a history of prior MI and in those with multiple risk factors. The renal‐specific outcome was reduced with dapagliflozin with HR ranging from 0.79(0.47–1.34) in patients with diabetes duration ≤5 years to 0.42(0.25–0.72) in those >20 years (interaction‐trend‐p‐value 0.084). Conclusions Dapagliflozin reduced the risk for CVD/HHF consistently, regardless of diabetes duration, whereas the treatment effect for MACE differed by duration subgroups, with significant reductions with dapagliflozin in patients with longer‐standing diabetes.