Ipragliflozin Reduces Epicardial Fat Accumulation in Non-Obese Type 2 Diabetic Patients with Visceral Obesity: A Pilot Study

INTRODUCTION: Epicardial fat (EF) was reported to be independently associated with cardiovascular disease regardless of obesity. We have previously reported that a sodium-glucose co-transporter-2 (SGLT2) inhibitor, luseogliflozin, reduces the EF volume (EFV) in parallel with the reduction of body weight in obese patients (BMI ≥25 kg/m(2)) with type 2 diabetes. However, it is unknown whether SGLT2 inhibitors could reduce EFV in non-obese patients (BMI <25 kg/m(2)) with type 2 diabetes. Therefore, we evaluated the effect of SGLT2 inhibitors on the EFV in non-obese type 2 diabetic patients with visceral obesity in this pilot study. METHODS: Nine of type 2 diabetic patients (mean age 66 ± 8 years; 33% female) with HbA(1c) 6.5–9.0%, body mass index (BMI, kg/m(2)) <25.0, and visceral fat area (VFA, cm(2)) ≥100 were enrolled. Participants were administered ipragliflozin 50 mg daily. EFV [median (interquartile range), cm(3)] was measured by magnetic resonance imaging. Primary endpoint was the change in EFV at 12 weeks. VFA and liver attenuation index (LAI), skeletal muscle index (SMI), and body fat (%) were also assessed at baseline and at 12 weeks. RESULTS: The EFV was significantly reduced from 102 (79–126) cm(3) to 89 (66–109) cm(3) by ipraglifrozin (p = 0.008). The body weight, BMI, HbA(1c), fasting plasma glucose, insulin, homeostasis model assessment-insulin resistance, triglycerides, leptin, body fat, android, gynoid, and VFA were significantly reduced and high-density lipoprotein cholesterol was significantly increased by ipraglifrozin at 12 weeks, whereas SFA and LAI were unchanged. The change in EFV was significantly correlated with the change in BMI. CONCLUSIONS: A12-week intervention of ipragliflozin reduced the EFV in non-obese type 2 diabetic patients with visceral adiposity. CLINICAL TRIAL REGISTRATION: UMIN Clinical Trial Registry: UMIN000019071. FUNDING: Astellas Pharma Inc. and the Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.