Effectiveness of drug interventions in nonalcoholic fatty liver disease: A network meta-analysis

Background Nonalcoholic fatty liver disease (NAFLD) is a major chronic liver disorder worldwide, and there is no established treatment for this disease. We conducted a network meta-analysis (NMA) to compare existing treatments, which include four classes of antidiabetic drugs, and examined the optimum treatments for NAFLD. Aim To compare the effectiveness of different treatments for NAFLD. Methods An NMA was conducted using Stata 14.0 (Corporation LLC, College Station, United States) and R (X64 3.6.3 version) in this study. Eligible randomized controlled trials (RCTs) were searched in the PubMed, Cochrane Library, Embase, Medline and Web of Science databases from database inception to April 2021. Two researchers independently screened the available studies in strict accordance with inclusion and exclusion criteria. The Cochrane Risk of Bias tool was used to evaluate the risk of bias of the included studies. The variables with and without dimensional differences were calculated as the standardized mean difference and weighted mean difference, respectively. An inconsistency model and "node-splitting" technique were used to test for inconsistency. Funnel plots were used to evaluate publication bias. Results Twenty-two eligible RCTs involving 1377 participants were eventually included in our analysis. Data were pooled using a random-effects model. Our NMA results revealed that glucagon-like peptide-1 receptor agonists (GLP-1RAs) were the most effective treatment, yielding improvements in hepatic fat content (HFC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum γ-glutamyl transferase (GGT) and body weight [surface under the cumulative ranking curve (SUCRA) = 99.6%, 92.6%, 82.8%, 92.3% and 99.6%, respectively], while thiazolidinediones (TZDs) were the best intervention for reducing the NAFLD activity score (NAS; SUCRA = 98.9%). In addition, moderate performance was observed for the sodium glucose cotransporter-2 inhibitors groups (SUCRA = 25.1%, 66.2%, 63.5%, 58.2% and 71.9% for HFC, ALT, AST, GGT and body weight, respectively). However, metformin performed poorly according to most indicators (SUCRA = 54.5%, 0.3%, 19.5%, 33.7%, 57.7% and 44.3% for HFC, NAS, ALT, AST, GGT and body weight, respectively). Conclusion GLP-1RAs may be the optimum choice for most patients with NAFLD. However, TZDs are considered the most effective therapies in NAFLD patients with histological disease activity.