Effect of Empagliflozin Versus Placebo on Plasma Volume Status in Patients with Acute Myocardial Infarction and Type 2 Diabetes Mellitus

INTRODUCTION: Plasma volume status (PVS), a parameter of the discrepancy between actual plasma volume (PV) and ideal PV, has been recently evaluated as a prognostic marker in patients with heart failure. This subgroup analysis of the EMBODY trial was designed to determine whether a sodium-glucose cotransporter 2 (SGLT2) inhibitor affects the alleviation of heart failure and improvement of PVS in patients after acute myocardial infarction (AMI) with congestive heart failure (CHF). METHODS: The EMBODY trial was a prospective, multicenter, randomized, double-blind, placebo-controlled trial to identify the effect of an SGLT2 inhibitor on cardiac sympathetic hyperactivity in patients with AMI and type 2 diabetes mellitus (T2DM) in Japan. In total, 105 patients were randomized (1:1) to receive 10 mg empagliflozin or a placebo (once daily), 2 weeks after the onset of AMI. In this subanalysis, we investigated the time-course of PVS at baseline and weeks 4, 12, and 24. RESULTS: Overall, 96 patients were included in the subgroup analysis set (age 64.3 ± 10.9 years, 80.2% men; 46 in the empagliflozin group and 50 in the placebo group). Body weight and PVS decreased in the empagliflozin group compared with the placebo group at 24 weeks (− 2.2 vs. + 0.1 kg, P < 0.001, and − 5.1 vs. − 0.3%, P < 0.001, respectively). Decreased PVS, defined as a change in PVS of < − 4.5%, was associated with the administration of empagliflozin (odds ratio 2.61, 95% confidence interval 1.11–6.15, P = 0.028). N-terminal pro b-type natriuretic peptide levels decreased in both the empagliflozin and placebo groups (1028.7–370.3 pg/mL, P < 0.001, and 1270.6–673.7 pg/mL, P < 0.01, respectively). CONCLUSION: Empagliflozin reduced the body weight and PVS. Early SGLT2 inhibitor administration in patients with AMI, CHF, and T2DM can therefore be effective in reducing the body weight and PVS. TRIAL REGISTRATION: UMIN 000030158.