GLP-1 receptor agonists ranked as the most broadly beneficial drug class for , while TZDs, SGLT-2 inhibitors, and vitamin E had narrower tradeoffs.
Evidence
A Bayesian network meta-analysis of 26 randomized controlled trials with 2143 patients compared hypoglycemic drugs and vitamin E across anthropometric, biomarker, hepatic fat, and biopsy outcomes.
Caveat
Most findings were only moderate-certainty, and current evidence was insufficient for SGLT-2 inhibitors on liver fat content or histological outcomes.
Simplified
BACKGROUND: Non-alcoholic fatty liver disease (), 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.
METHODS: 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).
RESULTS: 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 (), 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.
CONCLUSIONS: 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.
Key numbers
2143 patients
Total Patients
Included across 26 randomized controlled trials.
MD - 1.20
Weight Loss (SGLT-2I)
95% - 1.83 to - 0.71.
MD - 12.96
Liver Enzyme Reduction (ALT)
95% - 19.24 to - 6.86.
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