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

Niels Brandt-Jacobsen, Mikkel Jürgens, Phillip Hasbak, Peter Gæde, Peter Rossing, Jon Rasmussen, Camillla Fuchs Andersen, Julie Forman, Jens Faber, Silvio Inzucchi, Finn Gustafsson, Morten Schou (+1 others)
2022 Journal of the Endocrine Society  
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
more » ... 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
doi:10.1210/jendso/bvac150.504 fatcat:hp3odg333fda5j3ylrwgebimc4