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

Abstract

IntroductionEpicardial 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/m2) with type 2 diabetes. However, it is unknown whether SGLT2 inhibitors could reduce EFV in non-obese patients (BMI <25 kg/m2) 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.MethodsNine of type 2 diabetic patients (mean age 66 ± 8 years; 33% female) with HbA1c 6.5–9.0%, body mass index (BMI, kg/m2) <25.0, and visceral fat area (VFA, cm2) ≥100 were enrolled. Participants were administered ipragliflozin 50 mg daily. EFV [median (interquartile range), cm3] 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.ResultsThe EFV was significantly reduced from 102 (79–126) cm3 to 89 (66–109) cm3 by ipraglifrozin (p = 0.008). The body weight, BMI, HbA1c, 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.ConclusionsA12-week intervention of ipragliflozin reduced the EFV in non-obese type 2 diabetic patients with visceral adiposity.Clinical Trial RegistrationUMIN Clinical Trial Registry: UMIN000019071.FundingAstellas Pharma Inc. and the Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

Effects of ipragliflozin on glycemic control, appetite and its related hormones: A prospective, multicenter, open‐label study (SOAR‐KOBE Study)

“…Furthermore, the present results suggest that ipragliflozin reduced the serum leptin concentration and might thereby have increased appetite. SGLT‐2 inhibitors have been found to reduce serum leptin levels, but a reduction in the circulating leptin concentration adjusted for bodyweight has not previously been reported. The present study thus suggests that ipragliflozin might have reduced the circulating leptin concentration by an unknown mechanism.…”

Evaluation of the effects of sodium–glucose co‐transporter 2 inhibition with empagliflozin on morbidity and mortality in patients with chronic heart failure and a preserved ejection fraction: rationale for and design of the EMPEROR‐Preserved Trial

“…Treatment with SGLT2 inhibitors is poised to ameliorate many of the pathophysiological abnormalities seen in HFpEF. 14 In clinical trials, the use of SGLT2 inhibitors has been shown to reduce the quantity of epicardial adipose tissue (independently of effect on body weight), [35][36][37] and these drugs ameliorate the inflammation of adipose tissue surrounding the heart and great vessels 38,39 and the associated abnormalities of cardiac filling and aortic distensibility in both experimental and clinical HFpEF. 18,[40][41][42] Furthermore, SGLT2 inhibitors act to inhibit sodium reabsorption in the proximal renal tubules, in which the majority of renal sodium retention occurs [43][44][45] ; this action explains the marked reduction in plasma and/or interstitial volume and haemoconcentration seen in randomized controlled trials in type 2 diabetes.…”

Use of sodium‐glucose co‐transporter‐2 inhibitors in patients with type 2 diabetes mellitus and multiple cardiovascular risk factors: An Asian perspective and expert recommendations

“…In epidemiological surveys, epicardial fat volume (EFV) is shown to be positively correlated with the risk of atherosclerosis and coronary events . In Japanese patients with T2DM with or without obesity, ipragliflozin and luseogliflozin reduced EFV (measured by magnetic resonance imaging) at 12 weeks (change from baseline: luseogliflozin, 6 cm 3 , P = 0.048; ipragliflozin, 13 cm 3 ; P = 0.008), which correlated with reduction in circulating CRP levels …”