Comparative efficacy of Western medications for NAFLD

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Created On: 24/07/2025

With its growing global prevalence, nonalcoholic fatty liver disease (NAFLD) has become a key cause of liver-associated health issues.

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Key take away

Among Western treatments, pioglitazone delivers the strongest overall benefits for NAFLD, while aldafermin and resmetirom provide the greatest improvements in liver enzyme levels.

Background

With its growing global prevalence, nonalcoholic fatty liver disease (NAFLD) has become a key cause of liver-associated health issues. Western pharmacotherapies are commonly used in its management, yet their relative efficiency is ambiguous. Hence, this systematic review and bayesian network meta-analysis explored the efficacy of commonly prescribed Western medications for NAFLD.

Method

Researchers carried out a systematic search of Embase, Cochrane Library, PubMed, China National Knowledge Infrastructure (CNKI), WanFang, and China Science and Technology Journal Database. Eligible studies were randomized controlled trials (RCTs) involving NAFLD-affected adults (≥18 years), comparing Western medications against placebo or alternative Western treatments. On the basis of Surface Under the Cumulative Ranking Curve (SUCRA) values, treatments were ranked. Through I² and Q statistics, heterogeneity was evaluated. Visualizations and network plots were created using Stata 14.0.

Result

In total, 37 trials encompassing 7,673 patients were included. Pioglitazone illustrated the highest efficacy in mitigating nonalcoholic steatohepatitis (NASH) without fibrosis progression, escalating high-density lipoprotein cholesterol (HDL-C), and attaining a ≥2-point drop in NAFLD activity score (Odds ratio = 0.09), with a SUCRA probability of 91.4%.

Aldafermin portrayed strong improvements in liver enzymes. This encompassed alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyl transpeptidase, with SUCRA probabilities of 90% for ALT and 69.8% for AST. Cluster analyses identified resmetirom and aldafermin as top agents for liver function enhancement, while pioglitazone led in overall NAFLD improvement.

Conclusion

Among the evaluated Western medications, pioglitazone illustrated the most comprehensive efficacy for relieving NAFLD. However, aldafermin and resmetirom offered superior benefits in improving liver enzyme levels. These findings support tailored clinical use of these Western therapies to optimize patient outcomes.