Antidiabetic Medications for Type 2 Diabetics with Nonalcoholic Fatty Liver Disease: Evidence From a Network Meta-Analysis of Randomized Controlled Trials

Published:September 30, 2021DOI:https://doi.org/10.1016/j.eprac.2021.09.013

      Abstract

      Objective

      Type 2 diabetes mellitus and nonalcoholic fatty liver disease (NAFLD) are closely related, and antidiabetic medications have been shown to be potential therapeutics in NAFLD. Using a network meta-analysis, we sought to examine the effectiveness of antidiabetic agents for the treatment of NAFLD in patients with type 2 diabetes mellitus.

      Methods

      Medline and Embase were searched for randomized controlled trials relating to the use of antidiabetic agents, including sodium-glucose transport protein 2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists, and peroxisome proliferator-activated receptor gamma (PPARγ) agonists, biguanides, sulfonylureas and insulin, on NAFLD in patients with diabetes. The p-score was used as a surrogate marker of effectiveness.

      Results

      A total of 14 articles were included in the analysis. PPARγ agonists were ranked as the best treatment in steatosis reduction, resulting in the greatest reduction of steatosis. There was statistical significance between PPARγ agonists [mean difference (MD): −6.02%, confidence interval (CI): −10.37% to −1.67%] and SGLT2 inhibitors (MD: −2.60%, CI: −4.87% to −0.33%) compared with standard of care for steatosis reduction. Compared with PPARγ agonists, SGLT2 inhibitors resulted in a statistical significant reduction in fibrosis (MD: −0.06, CI: −0.10 to −0.02). Body mass index reduction was highest in SGLT2 inhibitors and glucagon-like peptide-1 receptor agonists. Additionally, SGLT2 inhibitors were ranked as the best treatment for increasing high-density lipoprotein and reducing low-density lipoprotein.

      Conclusion

      Glucagon-like peptide-1 receptor agonists and SGLT2 inhibitors were suitable alternatives for the treatment of NAFLD in those with type 2 diabetes mellitus with a reduction in body mass index, fibrosis, and steatosis. SGLT2 inhibitors also have the added benefit of lipid modulation.

      Key words

      Abbreviations:

      ALT (alanine aminotransferase), AST (aspartate aminotransferase), BMI (body mass index), CI (confidence interval), FIB4 (fibrosis-4), GLP-1R (glucagon-like peptide-1 receptor), HDL (high-density lipoprotein), LDL (low-density lipoprotein), MD (mean difference), MRI-PDFF (magnetic resonance imaging–derived proton density fat fraction), NAFLD (nonalcoholic fatty liver disease), NASH (nonalcoholic steatohepatitis), PPARγ (peroxisome proliferator-activated receptor gamma), RCT (randomized controlled trial), SGLT2 (sodium-glucose transport protein 2), T2DM (type 2 diabetes mellitus)
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