Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Objectives: This study sought to evaluate the effects of empagliflozin on extracellular volume (ECV) in individuals with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD). Background: Empagliflozin has been shown to reduce left ventricular mass index (LVMi) in patients with T2DM and CAD. The effects on myocardial ECV are unknown. Methods: This was a prespecified substudy of the EMPA-HEART (Effects of Empagliflozin on Cardiac Structure in Patients with Type 2 Diabetes) CardioLink-6 trial in which 97 participants were randomized to receive empagliflozin 10 mg daily or placebo for 6 months. Data from 74 participants were included: 39 from the empagliflozin group and 35 from the placebo group. The main outcome was change in left ventricular ECV from baseline to 6 months determined by cardiac magnetic resonance (CMR). Other outcomes included change in LVMi, indexed intracellular compartment volume (iICV) and indexed extracellular compartment volume (iECV), and the fibrosis biomarkers soluble suppressor of tumorgenicity (sST2) and matrix metalloproteinase (MMP)-2. Results: Baseline ECV was elevated in the empagliflozin group (29.6 ± 4.6%) and placebo group (30.6 ± 4.8%). Six months of empagliflozin therapy reduced ECV compared with placebo (adjusted difference: –1.40%; 95% confidence interval [CI]: –2.60 to –0.14%; p = 0.03). Empagliflozin therapy reduced iECV (adjusted difference: –1.5 ml/m2; 95% CI: –2.6 to –0.5 ml/m2; p = 0.006), with a trend toward reduction in iICV (adjusted difference: –1.7 ml/m2; 95% CI: –3.8 to 0.3 ml/m2; p = 0.09). Empagliflozin had no impact on MMP-2 or sST2. Conclusions: In individuals with T2DM and CAD, 6 months of empagliflozin reduced ECV, iECV, and LVMi. No changes in MMP-2 and sST2 were seen. Further investigation into the mechanisms by which empagliflozin causes reverse remodeling is required. (Effects of Empagliflozin on Cardiac Structure in Patients With Type 2 Diabetes [EMPA-HEART]; NCT02998970)

Original publication




Journal article


JACC: Cardiovascular Imaging

Publication Date





1164 - 1173