Sodium-glucose cotransporter protein-2 inhibitors and glucagon-like peptide-1 receptor agonists versus thiazolidinediones for non-alcoholic fatty liver disease: A network meta-analysis

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Abstract
Aims Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disorders worldwide. Some hypoglycemic drugs can improve NAFLD. However, it is unclear which of these types of hypoglycemic drugs are more effective for NAFLD. Therefore, we conducted a network meta-analysis to determine the effect of thiazolidinediones (TZDs), sodium-glucose cotransporter 2 (SGLT2) inhibitors, and glucagon-like peptide-1 (GLP-1) receptor agonists on NAFLD patients. Methods A literature search of PubMed, EMBASE, the Cochrane Library, and Medline was conducted, and the literature from database inception up to April 30, 2021 was obtained. Liver function tests, lipid profiles, body mass index (BMI) and glycemic parameters were obtained from randomized controlled trials. Weighted mean differences (WMDs), relative risks and 95% confidence intervals (CIs) were calculated for continuous outcomes, and the I2 statistic was used to evaluate the heterogeneity of the studies. Results In total, 22 trials, including 1361 patients, were selected. In direct meta-analysis, GLP-1 receptor agonists were superior to TZDs in decreasing alanine aminotransferase (WMD, −0.40, 95% CI: −0.60 to −0.20), γ-glutamyl transferase (WMD, −5.00, 95% CI: −6.47 to −3.53), BMI (WMD, −4.10, 95%CI: −6.55 to −1.65) and triglycerides (WMD, − 0.50, 95% CI: −0.68 to −0.32). Based on Bayesian network meta-analysis, the effect of SGLT-2 inhibitors on weight loss was superior to that of TZDs (WMD, −1.80, 95%CI: −3.30 to −0.41). Conclusions GLP-1 receptor agonists and SGLT-2 inhibitors improved liver enzymes, BMI, blood lipid, blood glucose and insulin resistance in NAFLD patients.
Funding Information
  • National Natural Science Foundation of China (81974281)
  • Natural Science Foundation of Hunan Province (2020JJ2052)
  • Chinese Cardiovascular Association-Access Fund (2019-CCA-ACCESS-2020JJ2052)

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