Luseogliflozin reduces epicardial fat accumulation in patients with type 2 diabetes: a pilot study

<jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Accumulation of epicardial fat (EF) is associated with increased cardio-metabolic risks and coronary events, independently of traditional cardiovascular risk factors. Therefore, the reduction of EF volume (EFV) may be associated with reduced cardio-metabolic risks and future cardiovascular events. Sodium-glucose co-transporter-2 (SGLT2) inhibitors reduce body fat including visceral fat and cardiovascular events in patients with type 2 diabetes. However, it has still been unknown whether SGLT2 inhibitors can reduce EFV.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>Type 2 diabetic patients with HbA1c 6.5–9.0% and body mass index (BMI, kg/m<jats:sup>2</jats:sup>) ≥25.0 were enrolled in this single arm pilot study. Participants were administered luseogliflozin 2.5 mg daily and the dosage was tolerated to be increased up to 5.0 mg daily. EFV [median (interquartile range), cm<jats:sup>3</jats:sup>] was measured by magnetic resonance imaging. Primary endpoint was the decrease in EFV at 12 weeks. Visceral fat area (VFA, cm<jats:sup>2</jats:sup>) and liver attenuation index (LAI) measured by the abdominal computed tomography, and skeletal muscle index (SMI) and body fat (%) measured by the whole body dual-energy X-ray absorptiometry were also determined at baseline and at 12 weeks.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>Nineteen patients (mean age: 55 ± 12 years; 26% female) completed this study. Luseogliflozin treatment significantly reduced EFV at 12 weeks [117 (96–136) to 111 (88–134), p = 0.048]. The body weight, BMI, systolic and diastolic blood pressure, HbA1c, fasting plasma glucose, insulin, homeostasis model assessment-insulin resistance (HOMA-IR), triglycerides, SMI, and body fat were significantly reduced by luseogliflozin at 12 weeks. The reduction of EFV was significantly correlated with the reduction of C-reactive protein (r = 0.493, p = 0.019). Neither VFA nor LAI were significantly reduced by the luseogliflozin treatment. No severe adverse events were observed.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Our data suggest that luseogliflozin could reduce the EFV in parallel with the improvement of systemic micro-inflammation and the reduction of body weight in Japanese patients with type 2 diabetes. The reduction of muscle mass after the administration of SGLT2 inhibitors may require a particular attention.</jats:p> <jats:p><jats:italic>Trial registration</jats:italic> umin.ac.jp, UMIN000019072</jats:p> </jats:sec>