31-OR: Ipragliflozin Ameliorated Overweight and Pathological Liver Fibrosis in Diabetic Patients with Nonalcoholic Fatty Liver Disease in a Multicenter Randomized Controlled Trial

Background: Ipragliflozin (IPR) is a sodium-glucose cotransporter 2 inhibitor (SGLT2i) used to treat diabetes. Given the global increase in diabetes and nonalcoholic fatty liver disease (NAFLD), the effects of SGLT2i on hepatic outcomes and glycemic control are of interest. Methods: The current study was a multicenter randomized controlled trial, and all patients included were diabetics with liver biopsy-proven NAFLD. They were divided into an IPR group (n = 24) administered IPR orally (50 mg/day), and a control group (CTR; n = 26) who undertook enhanced lifestyle modifications including diet and exercise therapy and/or antidiabetic drugs other than SGLT2i, pioglitazone, or GLP-1 analogs. After 72 weeks, a second liver biopsy was performed and clinical parameters including pathological indicators were compared in the two groups. All liver biopsies were evaluated by two expert pathologists. Results: There were no significant differences in basal bodyweight, hemoglobin A1c, or pathological NAFLD findings between the groups. Mean bodyweight reduction from baseline at 72 weeks was significantly greater in the IPR group (-3.2 vs. -0.4, p < 0.01). Compared to the CTR group, hemoglobin A1c was significantly lower at 48 weeks (-0.46 vs. -0.09, p < 0.05). The mean decrease in visceral fat area determined with CT scan was significantly greater in the IPR group. Neither AST nor ALT differed significantly between the groups. Liver fibrosis improved in 57.1% of patients in the IPR group and 16% in the CTR group (p < 0.01). Liver steatosis improved in 19.0% of patients in the IPR group and 28% in the CTR group (p > 0.05; not significant). Low-grade adverse events were observed in both groups. Conclusion: IPR reduces bodyweight and hemoglobin A1c in diabetics with NAFLD, and ameliorates liver fibrosis. Long-term IPR administration improves hepatic outcomes of NAFLD, and obesity and glycemic control. Disclosure H. Takahashi: Research Support; Self; Astellas Pharma Inc. T. Kessoku: None. M. Kawanaka: None. M. Nonaka: None. H. Hyogo: None. H. Fujii: None. T. Nakajima: None. K. Imajo: None. K. Tanaka: None. Y. Kubotsu: None. H. Isoda: None. S. Oeda: None. O. Kurai: None. M. Yoneda: None. M. Ono: None. A. Takamori: None. R. Tajiri: None. A. Kawaguchi: None. S. Aishima: None. M. Kage: None. A. Nakajima: Consultant; Self; Kowa Company, Ltd. Speaker’s Bureau; Self; Astellas Pharma Inc., Mylan. Y. Eguchi: None. K. Anzai: Research Support; Self; Astellas Pharma Inc., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk Inc. Speaker’s Bureau; Self; Daiichi Sankyo, Kyowa Hakko Kirin Co., Ltd., Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited. Funding Astellas Pharma Inc.