Comparison of sodium-glucose cotransporter-2 inhibitors and thiazolidinediones for management of non-alcoholic fatty liver disease: A systematic review and meta-analysis.

BACKGROUND: The pharmacologic treatment of non-alcoholic fatty liver disease (NAFLD) remains unclear.

METHODS: Two reviewers searched PubMed, SCOPUS, Cochrane Central and clinicaltrials.gov for randomized controlled trials (RCTs) of patients with NAFLD with or without type 2 diabetes mellitus (T2DM) receiving TZDs vs SGLT2 inhibitors. The primary outcomes were change in alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT) and improvement in steatosis and fibrosis. The secondary outcomes were changes in lipid profile, body weight and glycated hemoglobin (HbA1c). Random effects models with continuous outcomes as weighted mean differences (WMD) with 95% confidence intervals (CI) were used.

RESULTS: Five studies (n = 311 NAFLD patients) were included. Patients treated with SGLT2 inhibitors (n = 156) showed significant decrease in visceral fat area (VFA; WMD 23.45, p < 0.00001) and body weight (WMD 4.22, p < 0.00001) as compared to those treated with TZDs (n = 155). Patients from both groups showed improvement in AST (WMD 1.21, p = 0.40), ALT (WMD -0.46, p = 0.81), GGT (WMD -0.47, p = 0.84), hepatic fibrosis (WMD 0.11, p = 0.52), LDL (WMD 2.19, p = 0.35), HbA1c (WMD -0.16%, p = 0.20), HOMA-IR (WMD: -0.04, p = 0.91) and FPG (WMD -7.37, p = 0.28) which was equivalent and non-significant.

CONCLUSION: The improvement in liver enzymes, steatosis and fibrosis caused by SGLT2 inhibitors and TZDs was similar. SGLT2 inhibitors, however, resulted in a significant decrease in VFA and body weight. As weight loss is found to have a positive effect on the resolution of steatosis and fibrosis in NAFLD patients, SGLT2 inhibitors may have the potential to be considered for long-term management, however, further research needs to be conducted to determine the utility of SGLT2 inhibitor class of antidiabetic drugs for effectively treating NAFLD.