Rationale and design of the effects of EMpagliflozin on left ventricular DIAstolic function in diabetes (EmDia) study.

ABSTRACT

BACKGROUND: Data of the EMPA-REG OUTCOME study have demonstrated a beneficial effect of the sodium-glucose cotransporter 2 inhibitor empagliflozin on cardiovascular outcome in patients with type 2 diabetes. The reduction in cardiovascular mortality and hospitalization due to heart failure might be in part explained by the direct effects of empagliflozin on cardiac diastolic function. The EmDia trial investigates the short-term effects of empagliflozin compared to placebo on the left ventricular E/E' ratio as a surrogate of left ventricular diastolic function. METHODS: EmDia is a single-center, randomized, double-blind, two-arm, placebo-controlled, parallel group study of phase IV. Individuals with diabetes mellitus type 2 (T2DM) are randomized 11 to receive empagliflozin 10 mg per day or a placebo for 12 weeks. The main inclusion criteria are diagnosed as T2DM with stable glucose-lowering and/or dietary treatment, elevated HbA1c level (6.5-10.0% if receiving glucose-lowering therapy, or 6.5-9.0% if drug-naïve), and diastolic cardiac dysfunction with left ventricular E/E'≥8. The primary end point is the difference of the change in the E/E' ratio by treatment groups after 12 weeks. Secondary end points include assessment of the effect of empagliflozin on left ventricular systolic function, measures of vascular structure and function, as well as humoral cardiovascular biomarkers (i.e. brain natriuretic peptide, troponin, C-reactive protein). In addition, the multidimensional biodatabase enables explorative analyses of molecular biomarkers to gain insights into possible mechanisms of the effects of empagliflozin on human health in a systems medicine-oriented, multiomics approach. CONCLUSION: By evaluating the short-term effect of empagliflozin with a comprehensive biobanking program, the EmDia Study offers an opportunity to primarily assess the effects on diastolic function but also to examine effects on clinical and molecular cardiovascular traits. TRIAL REGISTRATION ClinicalTrials.gov; NCT02932436. Registration date, 2016/10/13.