Evaluation of the effects of dapagliflozin, a sodium-glucose co-transporter-2 inhibitor, on hepatic steatosis and fibrosis using transient elastography in patients with type 2 diabetes and non-alcoholic fatty liver disease

Diabetes Obes Metab. 2019 Feb;21(2):285-292. doi: 10.1111/dom.13520. Epub 2018 Oct 2.

Abstract

Aims: To investigate the effects of dapagliflozin on liver steatosis and fibrosis evaluated in patients with type 2 diabetes and non-alcoholic fatty liver disease (NAFLD).

Materials and methods: In a randomized, active-controlled, open-label trial, 57 patients with type 2 diabetes and NAFLD were randomized to a dapagliflozin group (5 mg/d; n = 33) or a control group (n = 24) and were treated for 24 weeks. Hepatic steatosis and fibrosis were assessed using transient elastography to measure controlled attenuation parameter (CAP) and liver stiffness, respectively.

Results: Baseline liver stiffness measurement (LSM) was positively correlated with several markers and scoring systems for liver fibrosis. In week 24, there was a significant decrease in CAP from 314 ± 61 to 290 ± 73 dB/m (P = 0.0424) in the dapagliflozin group, while there was no significant change in the control group. In addition, LSM tended to decrease from 9.49 ± 6.05 to 8.01 ± 5.78 kPa in the dapagliflozin group. In 14 patients from this group with LSM values ≥8.0 kPa, indicating significant liver fibrosis, LSM decreased significantly from 14.7 ± 5.7 to 11.0 ± 7.3 kPa (P = 0.0158). Furthermore, serum alanine aminotransferase and γ-glutamyltranspeptidase levels decreased in the dapagliflozin group, but not in the control group, and visceral fat mass was significantly reduced in the dapagliflozin group.

Conclusions: Based on these findings, the sodium-glucose co-transporter-2 inhibitor dapagliflozin improves liver steatosis in patients with type 2 diabetes and NAFLD, and attenuates liver fibrosis only in patients with significant liver fibrosis, although the possibility cannot be excluded that a reduction in body weight or visceral adipose tissue by dapagliflozin may be associated with a decrease of liver steatosis or fibrosis.

Keywords: dapagliflozin; liver fibrosis; non-alcoholic fatty liver disease; transient elastography; type 2 diabetes.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Benzhydryl Compounds / pharmacology
  • Benzhydryl Compounds / therapeutic use*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Elasticity Imaging Techniques* / methods
  • Female
  • Glucosides / pharmacology
  • Glucosides / therapeutic use*
  • Humans
  • Lipid Metabolism / drug effects
  • Liver / diagnostic imaging
  • Liver / drug effects
  • Liver / pathology
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / diagnosis*
  • Liver Cirrhosis / drug therapy
  • Male
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease / complications
  • Non-alcoholic Fatty Liver Disease / diagnosis*
  • Non-alcoholic Fatty Liver Disease / drug therapy*
  • Prognosis
  • Sodium-Glucose Transporter 2 Inhibitors / pharmacology
  • Sodium-Glucose Transporter 2 Inhibitors / therapeutic use*
  • Treatment Outcome

Substances

  • Benzhydryl Compounds
  • Glucosides
  • Sodium-Glucose Transporter 2 Inhibitors
  • dapagliflozin