Comparative efficacy of multiple drugs for non-alcoholic fatty liver disease: a Bayesian network meta-analysis

Non-alcoholic fatty liver disease (NAFLD), now referred to as metabolic dysfunction-associated steatotic liver disease (MASLD), is the most prevalent chronic liver disease worldwide. However, it remains unclear which drug treatment is more effective. Therefore, we conducted a network meta-analysis to comprehensively compare the efficacy of several potentially beneficial hypoglycemic drugs and vitamin E in treating patients with NAFLD.

This Bayesian network meta-analysis searched PubMed, Embase, Web of Science, and the Cochrane Library for randomized controlled trials (RCTs). We employed random-effects models to calculate mean differences (MD), relative risk (RR), and 95% confidence intervals (CI). The study outcomes included anthropometric measurements, biological markers, hepatic fat content, and liver biopsy results. The protocol for this systematic review with network meta-analysis was registered on PROSPERO (CRD42024532600).

This analysis included 26 RCTs with 2143 patients. Based on the surface under the cumulative ranking curve and the network meta-analysis matrix, glucagon-like peptide-1 receptor agonists (GLP-1RA) demonstrated superior efficacy compared to other interventions, particularly in terms of weight loss, improvement in liver enzymes, resolution of non-alcoholic steatohepatitis (NASH), reduction of hepatic fat content, glycemic control, and improvement in insulin resistance. Additionally, compared to placebo, sodium-glucose cotransporter protein-2 inhibitors (SGLT-2I) showed moderate benefits in weight loss (body mass index: MD - 1.20, 95% CI - 1.83 to - 0.71; waist circumference: MD - 2.03, 95% CI - 3.32 to - 0.74) and reduction in liver enzyme levels (alanine aminotransferase: MD - 12.96, 95% CI - 19.24 to - 6.86; aspartate aminotransferase: MD - 9.53, 95% CI - 14.20 to - 5.06). Overall, thiazolidinediones (TZD) provided significant histological benefits; however, they also carried a risk of weight gain. Vitamin E was also found to improve liver enzyme levels and histological features. According to the GRADE framework assessment, most of these findings are supported by evidence of moderate certainty.

The present study suggests that GLP-1RA may be the optimal treatment for NAFLD patients. In addition, current evidence does not sufficiently evaluate the impact of SGLT-2I on reducing liver fat content or histological outcomes. The potential risk of weight gain associated with TZD appears to be a limitation to their use. Vitamin E may be a suitable option for nondiabetic patients with NAFLD.