Effects of Different Types of Oral Glucose-Lowering Drugs on Hepatic Fat Accumulation and Liver Function in Japanese Subjects with Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease—A Randomized, Open-Label, 3-Arm Active-Control Study
Authors: KINOSHITA TOMOE , SHIMODA MASASHI , NAKANISHI SHUHEI , MUNE TOMOATSU , KAKU KOHEI , KANETO HIDEAKI 
Published: June 2018

Objective: In this study, we compared the effects of different types of oral hypoglycemic agents on NAFLD in subjects with T2DM.
Methods: We conducted a randomized, open-label, 3-arm active-control trial in subjects with T2DM and NAFLD. A total of 98 subjects were randomly allocated either to dapagliflozin (SG, n=32), pioglitazone (TZ, n=33) or glimepiride (SU, n=33) group, and the subjects took these drugs for 28 weeks. The primary endpoint was a change of liver-to-spleen (L/S) ratio on CT.
Results: Baseline characteristics in the three groups were similar in various clinical parameters. SG, TZ and SU ameliorated glycemic control similarly. Body weight and visceral fat area (VFA) were significantly decreased only in SG group. Serum adiponectin level was increased in TZ group compared to other two groups. SG and TZ, but not SU, significantly increased L/S ratio and decreased ALT level, and the effects of SG and TZ on those parameters were comparable. In simple correlation analysis with all subjects, change of L/S ratio was negatively correlated with alteration of BMI, VFA, HbA1c and serum insulin, and positively associated with change of adiponectin level. Multiple linear regression analysis revealed that the decrease in VFA and the increase in adiponectin level contributed to improve NAFLD in subjects with T2DM. In addition, the common factor which improved NAFLD in all groups was reduced VFA. On the other hand, there were also some differences among three groups about which factors were correlated with the change of L/S ratio.
Conclusions: The present study showed the decreased VFA and increased adiponectin independently contributed to improve NAFLD in patients with T2DM. Furthermore, dapagliflozin and pioglitazone, exerted equivalent beneficial effects on NAFLD in subjects with T2DM, although the two drugs have different mechanism of action.

Disclosure
T. Kinoshita: None. M. Shimoda: Speaker's Bureau; Self; AstraZeneca. Research Support; Self; Taisho Pharmaceutical Co., Ltd. S. Nakanishi: Speaker's Bureau; Self; Sanofi. T. Mune: None. K. Kaku: Speaker's Bureau; Self; AstraZeneca. Advisory Panel; Self; Boehringer Ingelheim GmbH. Speaker's Bureau; Self; Mitsubishi Tanabe Pharma Corporation, MSD K.K.. Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Ono Pharmaceutical Co., Ltd.. Advisory Panel; Self; Sanwa Kagaku Kenkyusho Co., Ltd.. Speaker's Bureau; Self; Taisho Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceuticals, Japan Inc., Kowa Pharmaceuticals, Japan Inc.. Advisory Panel; Self; Astellas, Japan Inc. H. Kaneto: Research Support; Self; Sanofi, Novo Nordisk Inc., Eli Lilly and Company, Boehringer Ingelheim Pharmaceuticals, Inc., MSD K.K., Takeda Pharmaceuticals U.S.A., Inc., Ono Pharmaceutical Co., Ltd., Daiichi Sankyo Company, Limited, Mitsubishi Tanabe Pharma Corporation, Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Astellas Pharma US, Inc..