1Comparison in effects by three kinds of glucose‐lowering drugs on nonalcoholic fatty liver disease in cases with type 2 diabetes: A randomized, open‐label, 3‐arm active‐control study

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is often observed in subjects with type 2 diabetes mellitus (T2DM), and it is known that the presence of T2DM leads to the aggravation of NAFLD. The aim of this study is to compare the possible effects of three kinds of oral hypoglycemic agents on NAFLD in subjects with T2DM. MATERIALS AND METHODS: We conducted a prospective clinical trial (a randomized and open-label study) in subjects with T2DM and NAFLD. A total of 98 subjects were randomly allocated either to dapagliflozin (n=32), pioglitazone (n=33) or glimepiride (n=33) group, and the subjects took these drugs for 28 weeks. The primary endpoint was the change of liver-to-spleen (L/S) ratio on abdominal computed tomography (CT). RESULTS: There was no difference in baseline clinical characteristics among the three groups. Dapagliflozin, pioglitazone and glimepiride ameliorated hyperglycemia similarly. Body weight and visceral fat area (VFA) were significantly decreased only in dapagliflozin group. Serum adiponectin level was markedly increased in pioglitazone group compared to other two groups. Dapagliflozin and pioglitazone, but not glimepiride, significantly increased L/S ratio, and the effects of dapagliflozin and pioglitazone on L/S ratio were comparable. CONCLUSIONS: The present study showed the decrease of VFA and the increase of adiponectin level contributed to the improvement of NAFLD in subjects with T2DM. Furthermore, dapagliflozin and pioglitazone exerted equivalent beneficial effects on NAFLD in subjects with T2DM, although it seemed that these two drugs had different mechanism of action.