Ipragliflozin Additively Ameliorates Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Controlled with Metformin and Pioglitazone: A 24-Week Randomized Controlled Trial.

Eugene Han,Byung-Wan Lee,Yong-Ho Lee,Eun Seok Kang,Bong-Soo Cha

doi:10.3390/jcm9010259

Eugene Han, Byung-Wan Lee + Show 3 more

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https://doi.org/10.3390/jcm9010259

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Abstract

Despite the benefits of pioglitazone in the treatment of non-alcoholic fatty liver disease (NAFLD), many treated patients continue to experience disease progression. We aimed to investigate the additive effect of ipragliflozin on NAFLD in patients with type 2 diabetes treated with metformin and pioglitazone. In this 24-week randomized controlled trial, 44 patients with type 2 diabetes and comorbid NAFLD were either randomized to receive 50 mg/day of ipragliflozin as an add-on treatment (n = 29) or maintained on metformin and pioglitazone (n = 15). The fatty burden was assessed using the fatty liver index, NAFLD liver fat score, and controlled attenuation parameter (CAP). Changes in fat and muscle depots were measured by dual-energy x-ray absorptiometry and abdominal computed tomography scans. The enrolled patients were relatively controlled (mean baseline glycated hemoglobin of 6.6% ± 0.6%) and centrally obese (mean waist circumference of 101.6 ± 10.9 cm). At week 24, patients in the ipragliflozin add-on group exhibited reduced hepatic fat content (fatty liver index: −9.8 ± 1.9, p = 0.002; NAFLD liver fat score: −0.5 ± 0.2, p = 0.049; CAP: −8.2 ± 7.8 dB/m2, p = 0.133). Ipragliflozin add-on therapy also reduced whole-body visceral fat and the ratio of visceral to subcutaneous fat (change in whole-body visceral fat: −69.6 ± 21.5 g; change in abdominal visceral fat: −26.2 ± 3.7 cm2; abdominal visceral to subcutaneous fat ratio: −0.15 ± 0.04; all p < 0.05). In conclusion, ipragliflozin treatment significantly ameliorates liver steatosis and reduces excessive fat in euglycemic patients with type 2 diabetes and NAFLD taking metformin and pioglitazone.

Highlights

As obesity and type 2 diabetes (T2D) emerge as comorbid endemic diseases, management strategies have shifted to account for obesity and T2D-related complications
TZDs are ineffective in some patients with T2D and their use is associated with an increased risk for edema, fluid retention, and weight gain, subcutaneous fat gain [9]
The exclusion criteria for this study were: (1) diagnosis of type 1 diabetes, gestational diabetes, or any diabetes diagnosis other than type 2 diabetes; (2) history of addiction to alcohol, heavy alcohol consumption (≥210 g/week for men or ≥140 g/week for women), or patients with aspartate aminotransferase (AST), alanine aminotransferase (ALT), or bilirubin levels more than three times the upper normal limit; (3) other causes of liver disease, liver cirrhosis, or hepatocellular carcinoma; (4) estimated glomerular filtration rate < 60 mL/min/1.73 m2; (5) medication associated with fatty liver disease or weight loss; and (6) pregnant or nursing women

Summary

Introduction

As obesity and type 2 diabetes (T2D) emerge as comorbid endemic diseases, management strategies have shifted to account for obesity and T2D-related complications. Non-alcoholic fatty liver disease (NAFLD) is an obesity-related disease that is both a complication of and a risk factor for type 2 diabetes [1,2,3]. Thiazolidinediones (TZDs) are the first-line treatment for patients with comorbid T2D and NAFLD [4]. TZDs in patients with comorbid T2D and NAFLD have been shown to improve liver enzymes and hepatic histology [8]. TZDs are ineffective in some patients with T2D and their use is associated with an increased risk for edema, fluid retention, and weight gain, subcutaneous fat gain [9]. The response rate to TZD treatment is relatively low (approximately 50%) in NAFLD [8,10,11]

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