Effect of SGLT2 Inhibitors on Type 2 Diabetes Mellitus With Non-Alcoholic Fatty Liver Disease: A Meta-Analysis of Randomized Controlled Trials

Front Endocrinol (Lausanne). 2021 Jun 17:12:635556. doi: 10.3389/fendo.2021.635556. eCollection 2021.

Abstract

Objective: Clinical trials showed that sodium-glucose cotransporter 2 (SGLT2) inhibitors can improve non-alcoholic fatty liver disease (NAFLD). In this work, a meta-analysis of randomized controlled trials was conducted to evaluate the effect of SGLT2 inhibitors on type 2 diabetes mellitus (T2DM) with NAFLD.

Methods: PubMed, Embase, Web of Science, and Cochrane Libraries were used for the systematic literature review to determine eligible studies. A randomized effect model was adapted to perform a meta-analysis on these eligible studies to estimate the combined effect sizes. Differences were expressed as the weighted average difference (WMD) of the continuous results and the 95% confidence interval (CI).

Results: Ten randomized controlled trials with 573 participants were included. SGLT2 inhibitors significantly reduced the levels of alanine transaminase (WMD -5.36 [95% CI: -8.86, -1.85], p = 0.003) and Aspartate Transaminase (WMD -2.56 [95% CI: -3.83, -1.29], p <0.0001). In terms of body composition, liver proton density fat fraction (WMD -2.20 [95% CI: -3.67, -0.74], p = 0.003), visceral fat mass area (WMD -20.71 [95% CI: -28.19, -13.23], p <0.00001), subcutaneous fat areas (WMD -14.68 [95% CI: -26.96, -2.40], p = 0.02) were also significantly reduced.

Conclusion: SGLT2 inhibitors can remarkably reduce hepatic enzymes, hepatic fat and improve body composition. Thus, they may become a new treatment option for NAFLD.

Systematic review registration: PROSPERO, identifier CRD42020215570.

Keywords: liver proton density fat fraction; non-alcoholic fatty liver disease; sodium-glucose cotransporter 2 inhibitors; type 2 diabetes mellitus; visceral fat mass area.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Adipose Tissue / metabolism
  • Aged
  • Blood Glucose / analysis
  • Body Composition
  • Diabetes Complications
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Female
  • Homeostasis
  • Humans
  • Insulin Resistance
  • Male
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease / complications*
  • Non-alcoholic Fatty Liver Disease / drug therapy*
  • Randomized Controlled Trials as Topic
  • Sodium-Glucose Transporter 2 Inhibitors / pharmacology*

Substances

  • Blood Glucose
  • Sodium-Glucose Transporter 2 Inhibitors