Research into the Effect of Sodium-Glucose Linked Transporter 2 Inhibition on Left Ventricular Remodeling in Patients with Heart Failure and Diabetes Mellitus

Abstract

Introduction: DM and heart failure (HF) are lethal, with limited diabetic therapy options. Sodium-glucose linked transporter 2 (SGLT2) inhibitors have been reported to have CV benefits in at risk DM patients. We are the first to study the CV effects of SGLT2 inhibition in patients with DM and HF. Methods: In this randomized double-blind placebo controlled trial, 56 patients (mean age: 67.1 years, males: 66%) with DM and echocardiographically confirmed HF with reduced ejection fraction (HFrEF) on regular diuretic therapy were assigned to dapagliflozin 10mg OD or placebo for one year. Primary endpoint was the difference in left ventricular (LV) volumes between both groups using cardiac MRI. Secondary endpoints include LV mass, LV ejection fraction (EF), weight, BP and diuretic use. Outcomes were analysed using linear regression controlling for baseline values, age, sex and renal function. Results: There was no difference between dapagliflozin and placebo in the primary endpoints of LV end diastolic volume (LVEDV) or LV end systolic volume (LVESV); +4.71mls; 95% CI: -17.to 26.50 and +1.52mls; 95% CI: -15.68 to 18.72 respectively. However, when an interaction term for starting LVEF was added to the model, dapagliflozin significantly lowered LVEDV, LVESV and LV mass in those with starting LVEF ≥ 45%; -15.59mls; p=0.019, -15.20mls; p=0.016 and -4.87gm/m2; p=0.026. Patients on dapagliflozin had weight reduction; -1.90kg; 95% CI: -3.83 to +0.04; p=0.054, lower diastolic BP; -6.34mmHg; 95% CI: -11.35 to -1.32; p=0.014 and higher hemoglobin; +1.23 g/dl; 95% CI: 0.65 to 1.82; p<0.001. They were also more likely to stop or reduce loop diuretics; 50.0% vs. 8.7%; p=0.005. Conclusions: Our data show dapagliflozin treatment resulted in weight and blood pressure reduction among patients with DM and HFrEF. There was evidence to suggest that dapagliflozin may cause LV reverse remodelling in DM patients with mild, but not with more severe HFrEF. Disclosure J.S.S. Singh: None.I. Mordi: None.M. Mohan: None.S.J. Gandy: None. E. Pearson: Speaker's Bureau; Self; Eli Lilly and Company.J.G. Houston: None. A.D. Struthers: Research Support; Self; AstraZeneca. Advisory Panel; Self; AstraZeneca.C.C. Lang: None.