876-P: Empagliflozin-Induced Metabolic Changes and Cardiac Function in Patients with Type 2 Diabetes: A Randomized Crossover MRI Study with Insulin as Comparator

Abstract

Introduction: Empagliflozin reduces cardiovascular risk in type 2 diabetes, possibly through improved cardiac function associated with metabolic changes including lowered glucose and insulin concentrations and elevated free fatty acids (FFA) . We aimed to evaluate the influence of these metabolic changes on cardiac function in type 2 diabetes (T2D) . Materials and Method: 17 subjects (13 males) with T2D, aged 58±3 years (mean±sem) , BMI 32.9±0.9 kg/m2, HbA1c 52.4±2.4 mmol/L, TD2 duration of 8.9±1.3 years were treated with empagliflozin (E) and NPH-insulin (I) for 5 weeks in a cross-over design with 3 weeks of washout between treatments. Insulin was titrated to produce similar glycemic control as during empagliflozin. Patients were studied before and at the end of each treatment period. Metabolic changes were evaluated with fasting glucose, FFAs and insulin concentrations, cardiac function with cardiac MRI during rest and chronotropic stress on two separate days without and with acute lowering of FFAs with acipimox. Cardiac endpoints were changes in left ventricular peak filling rate (∆LVPFR) and left ventricular ejection fraction (∆LVEF) . Results: Fasting glucose was reduced from 8.7±0.5 mM during washouts to 7.6±0.3 mM on both treatments, while serum insulin was lower (E: 103±14 pM; I: 141±16 pM, p<0.01) and FFAs higher (E: 0.60±0.03 mM; I: 0.50±0.mM, p=0.02) on empagliflozin compared with insulin treatment. Cardiac function did not differ between treatments in rest or during stress (rest: ∆LVPFR E: -2±19;I: -11±20 ml/s, p=1.0; ∆LVEF -1 ±1, -1±1%, p=0.8; stress: ∆LVPFR E:-32±20, I: -14±24 ml/s; ∆LVEF E: 1±2, I: 0±2%) . Acipimox reduced FFAs by ∼35% at all visits but did not reveal any cardiac effects of treatments. Conclusion: Neither empagliflozin nor insulin treatment change cardiac function in patients with T2D. Treatment specific metabolic effects play no role for cardiac function under the studied conditions. Disclosure R.Thirumathyam: None. J.Goetze: Consultant; Novo Nordisk A/S. J.J.Holst: Advisory Panel; Novo Nordisk, Board Member; Antag Therapeutics, Bainan Biotech. N.Vejlstrup: None. S.Madsbad: None. P.L.Madsen: None. N.B.Jørgensen: Advisory Panel; Novo Nordisk A/S, Research Support; Boehringer Ingelheim International GmbH, Speaker's Bureau; Novo Nordisk A/S, Stock/Shareholder; Eli Lilly and Company, Novo Nordisk A/S. Funding Boehringer Ingelheim Gmbh. Investigator initiated study grant.