Objectives: This network meta-analysis (NMA) aimed to evaluate the relative rank-order of existing diabetes medications in patients with nonalcoholic fatty liver disease (NAFLD) with or without type 2 diabetes mellitus (T2DM).
Methods: A systematic literature search was conducted using the Medline, Embase and Cochrane databases. Clinical trials comparing the efficacy of diabetes medications with other interventions, including lifestyle modification and placebo, in patients with NAFLD were included. The results from the NMA are presented as the weighted mean difference (WMD) of the continuous results and the corresponding 95% confidence intervals (95% CIs).
Results: The articles presented the results of 49 trials involving 3,836 subjects published between 2013 and 2021. According to our results, thiazolidinedione (TZD) was ranked as the best diabetes medication in the reduction of alanine aminotransferase (ALT) (WMD = -10.10, 95% CI: -15.18, -5.01), followed by dipeptidyl peptidase-4 inhibitor (DPP4i) (WMD = -8.90, 95% CI: -14.41, -3.40). DPP4i also resulted in the greatest reduction in aspartate aminotransferase (AST) (WMD = -6.89, 95% CI: -11.72, -2.07). γ-Glutamyl transferase (γ-GT) reduction was highest in patients treated with glucagon-like peptide 1 receptor agonists (GLP1RAs) (WMD = -15.48, 95% CI: -30.93, -0.02). Ultimately, SGLT2is and GLP1RAs were superior to other diabetes medications or placebo in reducing liver fat fraction (LFF) (WMD = -6.09, 95% CI: -10.50, -1.68; WMD = -5.55, 95% CI: -10.40, -0.69, respectively).
Conclusion: Diabetes medications, including TZD, DPP4i and GLP1RAs, were found to be suitable alternatives for liver enzyme reduction in the treatment of NAFLD patients. SGLT2is are considered the most effective therapies for lipid modulation in these patients.
Keywords: Diabetes medications; Liver enzyme; Liver fat fraction; Network meta-analysis; Nonalcoholic fatty liver disease.
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