Sodium-glucose cotransporter-2 inhibitors improve liver enzymes in patients with co-existing non-alcoholic fatty liver disease: a systematic review and metanalysis

Introduction
Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis, inflammation, and fibrosis. While sodium-glucose cotransporter-2 (SGLT-2) inhibitors have been established to improve glycaemic control in type-2 diabetes mellitus (T2DM), evidence of the beneficial effects in diabetics with coexisting NAFLD has yet to be quantitatively summarized.

Material and methods
We searched the PubMed, Medline, CINAHL, and Cochrane databases and ClinicalTrial.gov from database inception to July 2020. We included randomized controlled trials assessing the impact of SGLT2 inhibitors on liver enzymes among patients with NAFLD. Our primary outcome included liver inflammation as measured using liver transaminase. Secondary outcomes included drug efficacy on hepatic steatosis and body mass index. Risk differences were calculated using a random model.

Results
A total of 10,555 patients were included in this meta-analysis (SGLT2 inhibitor group: n = 7125; control group: n = 3430). The treatment duration ranged from 8 to 52 weeks. Patients with T2DM, who were treated with SGLT2 inhibitor had decrease in ALT (SMD = –0.22, 95% CI: –0.27 to –0.20) and AST levels (SMD = –0.20, 95% CI: –0.31 to –0.08). The SGLT-2 inhibitor did not cause statistically significant weight loss (SMD = –0.21, 95% CI: –0.47 to 0.06), fibrosis regression utilizing FIB-4 score (SMD = –0.12, 95% CI: –0.41 to 0.18), and hepatic steatosis by using MRI-PDFF (SMD = –0.31, 95% CI: –0.68 to 0.07), as compared to controls.

Conclusions
The SGLT2 inhibitor treatment may improve liver function, as demonstrated in the statistically significant reduction in transaminase levels. There were also notable trends in improved liver fibrosis and steatosis across the study periods.