Efficacy and safety of dapagliflozin in patients with type 2 diabetes and concomitant heart failure

Abstract

Aim: We investigated the efficacy and safety of dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, in patients with type 2 diabetes mellitus (T2DM) and heart failure (HF).

Methods: Data for patients randomized to dapagliflozin 10mg or placebo with a history of HF were pooled from five clinical trials. HbA_1c, weight and systolic blood pressure (SBP; two studies) were examined up to 52weeks using longitudinal repeated-measures models. Composite cardiovascular outcomes, hospitalizations for HF (HHF), and adverse events (AEs) were also assessed.

Results: Patients (mean age 64years, T2DM duration ~14years, HbA_1c 8.2%, ~50% with New York Heart Association Class ≥II) received dapagliflozin (N=171) or placebo (N=149). Dapagliflozin produced clinically meaningful placebo-adjusted reductions in HbA_1c (-0.55%; 95% confidence interval [CI]: -0.80, -0.30), weight (-2.67kg; 95% CI: -3.88, -1.47), and SBP (-2.05mmHg; 95% CI: -5.68, 1.57) over 52weeks. HHF was rare, but numerically lower with dapagliflozin (n=1 [0.6%]) vs placebo (n=7 [4.7%]). Point estimates for hazard ratios of composite cardiovascular outcomes favored dapagliflozin vs placebo, although 95% CIs crossed unity.

Conclusions: Dapagliflozin produced clinically meaningful reductions in HbA_1c, weight, and SBP in patients with T2DM and HF, and was well tolerated.

Keywords: Cardiovascular safety; Dapagliflozin; Efficacy; Heart failure; Pooled analysis; Type 2 diabetes mellitus.