Dapagliflozin and Empagliflozin Ameliorate Hepatic Dysfunction Among Chinese Subjects with Diabetes in Part Through Glycemic Improvement: A Single-Center, Retrospective, Observational Study

Introduction: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) improve hepatic dysfunction, although studies focusing on their underlying mechanisms are lacking, especially ones on dapagliflozin and empagliflozin. Here, we investigated the relationship between amelioration of hepatic dysfunction and improvement in various metabolic parameters among Chinese subjects with type 2 diabetes (T2DM). Methods: This was a single-center, retrospective, observational study that involved 115 Chinese participants with T2DM treated with either dapagliflozin or empagliflozin for at least 6 months between July 2016 and February 2017. Results: Of the 115 participants included in this study, 69 received dapagliflozin and 46 received empagliflozin. After 6 months of treatment, all patients showed significant improvements in body weight (BW), systolic blood pressure (SBP) and fasting glucose (FG) and glycated hemoglobin (HbA1c) levels. All participants also showed a significant reduction in serum alanine aminotransferase (ALT) levels, from 40.3 +/- 28.0 to 29.0 +/- 14.1 U/L (p < 0.001). Pearson's correlation analysis revealed a positive correlation between the reduction in ALT levels after treatment with the respective SGLT2i and changes in FG (p = 0.014) and HbA1c (p = 0.043) levels over 6 months, but not with changes in BW and SBP. Multiple linear regression analysis revealed that the reduction in serum ALT levels was independently associated with changes in both HbA1c and FG but not with the changes in the other clinical variables, including BW. Conclusions: Dapagliflozin and empagliflozin improved both metabolic and hepatic dysfunction as a class effect. The amelioration of hepatic dysfunction was mediated partly through an alleviation of hyperglycemia and possibly through an improvement in insulin resistance, independent of BW.