Effect of sodium-glucose co-transporter 2 inhibitors on hepatic parameters: A systematic review and meta-analysis of randomized controlled trials

Pharmacol Res. 2021 Jan:163:105319. doi: 10.1016/j.phrs.2020.105319. Epub 2020 Nov 24.

Abstract

Previous studies have suggested that sodium-glucose co-transporter-2 (SGLT2) inhibitors may improve hepatic function; however, the evidence is scarce. Hence, we performed a meta-analysis of randomized controlled trials to evaluate the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors on hepatic parameters. PubMed, Web of Science, Scopus, and Google Scholar databases were searched to identify randomized controlled trials examining the effect of SGLT2 inhibitors on hepatic parameters. Meta-analysis was performed using a random-effects model and sensitivity analysis. Meta-analysis revealed that SGLT2 inhibitors therapy significantly lowered alanine aminotransferase (ALT) (WMD: -4.79 U/L, 95 % CI: -6.10, -3.47, I2 = 62 %, p < 0.00001), aspartate aminotransferase (AST) (WMD: -2.49 U/L, 95 % CI: -3.30, -1.68, I2 = 54 %, p < 0.00001), alkaline phosphatase (AP) (WMD: -1.13 U/L, 95 % CI: -2.03, -0.22, I2 = 23 %, p = 0.02), and gamma-glutamyl transferase (GGT) (WMD: -7.77 U/L, 95 % CI: -9.33, -6.21, I2 = 5 %, p < 0.00001). Additionally, SGLT2 inhibitors showed a significant increase in bilirubin levels (WMD: 0.64 U/L, 95 % CI: 0.27, 1.00, I2 = 53 %, p < 0.0006. Finally, no significant changes were found on albumin levels (WMD: 0.13 U/L, 95 % CI: -0.06, 0.32, I2 = 53 %, p < 0.0006) after SGLT2 inhibitors treatment. In conclusion, our results suggest that treatment with SGLT2 inhibitors exerts a beneficial effect on liver function tests through decreased ALT, AST, AP, and GGT concentrations.

Keywords: Hepatic function; Liver function tests; Meta-analysis; Sodium-glucose co-transporter-2 inhibitors.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Alanine Transaminase / blood
  • Alkaline Phosphatase / blood
  • Aspartate Aminotransferases / blood
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / drug therapy
  • Humans
  • Liver / drug effects*
  • Liver / metabolism
  • Randomized Controlled Trials as Topic
  • Sodium-Glucose Transporter 2 Inhibitors / pharmacology*
  • Sodium-Glucose Transporter 2 Inhibitors / therapeutic use
  • gamma-Glutamyltransferase / blood

Substances

  • Sodium-Glucose Transporter 2 Inhibitors
  • gamma-Glutamyltransferase
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Alkaline Phosphatase