Journal Article

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

Gause-Nilsson, Ingrid, Johnsson, Eva, Sonesson, Christian, Kosiborod, Mikhail, Xu, John

2017

Overview

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). Data for patients randomized to dapagliflozin 10mg or placebo with a history of HF were pooled from five clinical trials. HbA1c, 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. Patients (mean age 64years, T2DM duration ~14years, HbA1c 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 HbA1c (−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. Dapagliflozin produced clinically meaningful reductions in HbA1c, weight, and SBP in patients with T2DM and HF, and was well tolerated.

• Publisher: Elsevier Inc,Elsevier Limited
• Subject: Acute coronary syndromes / Adult / Aged / Aged, 80 and over / Antidiabetics / Benzhydryl Compounds - adverse effects / Benzhydryl Compounds - therapeutic use / Cardiovascular safety / Clinical trials / Dapagliflozin / Diabetes / Diabetes Mellitus, Type 2 - blood / Diabetes Mellitus, Type 2 - complications / Diabetes Mellitus, Type 2 - drug therapy / Diabetic Cardiomyopathies - epidemiology / Diabetic Cardiomyopathies - prevention & control / Diuretics, Osmotic - adverse effects / Diuretics, Osmotic - therapeutic use / Drug therapy / Efficacy / Endocrinology & Metabolism / Female / Glucose / Glucosides - adverse effects / Glucosides - therapeutic use / Glycated Hemoglobin A - analysis / Health risk assessment / Heart failure / Heart Failure - complications / Heart Failure - epidemiology / Heart Failure - prevention & control / Heart rate / Hospitalization / Humans / Hyperglycemia - prevention & control / Hypoglycemia / Hypoglycemia - chemically induced / Hypoglycemia - prevention & control / Hypoglycemic Agents - adverse effects / Hypoglycemic Agents - therapeutic use / Longitudinal Studies / Male / Membrane Transport Modulators - adverse effects / Membrane Transport Modulators - therapeutic use / Middle Aged / Mortality / Pooled analysis / Randomized Controlled Trials as Topic / Risk Factors / Secondary Prevention / Side effects / Sodium-Glucose Transport Proteins - antagonists & inhibitors / Sodium-Glucose Transport Proteins - metabolism / Stroke / Type 2 diabetes mellitus