ODP154 Reduction of Cardiac Adipose Tissue Volume with Short-Term Empagliflozin in Patients with Type 2 Diabetes: Results from the SIMPLE Randomized Clinical Trial

BACKGROUND: Sodium-glucose transporter 2 inhibitors (SGLT2-is) appear to have rapid clinical cardiovascular benefits in type 2 diabetes. Furthermore, SGLT2-is have known effects on fat metabolism. Cardiac adipose tissue (CAT) correlates with known markers of cardiovascular risk and left ventricular function. The effects of SGLT2-i treatment on CAT is largely unknown. OBJECTIVE: In this exploratory sub-study from the SIMPLE-trial, we investigated whether empagliflozin affects CAT volume in patients with type 2 diabetes. METHODS: Between April 4, 2017, and May 11, 2020, we randomized 90 patients with type 2 diabetes and established or high risk of cardiovascular disease to either 25 mg empagliflozin or placebo for 13 weeks. The primary focus of this sub-study was change in CAT evaluated by computer-tomography (CT). The analysis included 78 patients who had at least one CT scan. Furthermore, we investigated the effect of empagliflozin on left ventricular mass (LVM), end-diastolic volume (EDV) and end-systolic volume (ESV) evaluated by rest and stress 82Rubidium Positron Emission Tomography CT and changes in whole-body metabolism evaluated by fat mass distribution via dual x-ray absorptiometry and measurements of various parameters of glucose, ketone and lipid metabolism. RESULTS: Mean ±SD baseline CAT volume was 258.5 mL ±117.9. Empagliflozin reduced CAT after 13 weeks by 12.41 mL (95%CI [-23.83 to -0.99], P=0. 034) as compared with placebo. LVM (-5.16 g, 95%CI [-8.80 to -1.52], P=0. 006), EDV (-7.90 mL, 95%CI [-13.70 to -2.10], P=0. 008) and ESV (-5.46 mL 95%CI [-9.78 to -1.15], P=0. 014) decreased with empagliflozin when comparing groups at week 13. In addition, improvements were observed in whole body metabolic parameters: mean total body weight (-1.48 kg, 95%CI [-2.41 to -0.55], P=0. 002), total fat mass (-0.81 kg, 95%CI [-1.40 to -0.22], P=0. 008), fasting plasma (-1.82 mmol/L, 95%CI [-2.83 to -0.80], P=0. 001), HbA1c (NGSP: -0.76%, 95%CI [-1. 00 to -0.51], P<0. 001; IFCC: -8.28 mmol/mol, 95%CI [-11. 01 to -5.54], P<0. 001), beta-hydroxybutyrate (0. 07 mmol/L, 95%CI [0. 00 to 0.14], P=0. 044), and triglycerides (-16.1%, 95%CI [-27.3 to -3.2], P=0. 017), when comparing groups at week 13. We observed no significant correlation between changes in CAT and changes in LVM, EDV and ESV. CONCLUSION: Treatment with empagliflozin provides an early reduction of CAT and improves myocardial structure and function which may explain some of this SGLT2-i's clinical cardiovascular benefits. Presentation: No date and time listed