Effects of sodium-glucose co-transporter 2 inhibitors on liver parameters and steatosis: A meta-analysis of randomized clinical trials

Diabetes Metab Res Rev. 2021 Sep;37(6):e3413. doi: 10.1002/dmrr.3413. Epub 2020 Oct 12.

Abstract

Aims: Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in Western countries and a common comorbidity with type 2 diabetes (T2D). It lacks effective pharmacotherapy. We aimed to summarize the evidence on the effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on liver structure and function.

Materials and methods: Meta-analysis of randomized clinical trials in PubMed, Web of Science and ClinicalTrials.gov from their inception to April 2019. Trials evaluating liver function and/or structure and comparing SGLT2 inhibitors with placebo or other oral antidiabetic drugs in patients with T2D were included. Twenty studies (from 3033) were included. A total of 1950 patients with T2D, with or without NAFLD, were treated with SGLT2 inhibitors for at least 8 weeks, and 1900 patients were used as controls. Independent extraction was carried out by two observers. This study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis.

Results: SGLT2 inhibitors induced a significant decrease in serum alanine (-7.43U/L, [95%CI -12.14, -2.71], p < 0.01), in aspartate aminotransferases (-2.83U/L, [-4.71, -0.95], p < 0.01), as well as in gamma glutamyl transferase (-8.21U/L, [-9.52, -6.91], p < 0.01), and an increase in total plasma bilirubin (8.19% [0.79, 15.59], p < 0.01), comparing with placebo or other oral antidiabetic drugs. SGLT2 inhibitors treatment was associated with a decrease in liver steatosis (-3.39% [-6.01, -0.77], p < 0.0.1).

Conclusions: Treatment with SGLT2 inhibitors improves liver structure and function in patients with T2D. This meta-analysis suggests that SGLT2 inhibitors are a promising pharmacological approach for treatment of NAFLD.

Keywords: NAFLD; SGLT2 inhibitors; liver; metanalysis.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diabetes Mellitus, Type 2* / drug therapy
  • Glucose
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Non-alcoholic Fatty Liver Disease* / drug therapy
  • Randomized Controlled Trials as Topic
  • Sodium
  • Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use
  • Symporters*

Substances

  • Hypoglycemic Agents
  • Sodium-Glucose Transporter 2 Inhibitors
  • Symporters
  • Sodium
  • Glucose