Effectiveness and Safety of Resmetirom in the Treatment of Patients with Non-alcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis

Abstract Background: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are progressive liver diseases with limited treatment options. Resmetirom, a selective thyroid hormone receptor-β agonist, has been evaluated for its therapeutic potential. Methods: Randomized controlled trials (RCTs) assessing resmetirom in NAFLD/NASH were retrieved from PubMed, Embase, Cochrane Central Register of Controlled Trials and Web of Science up to December 2024. Primary outcomes included hepatic fat reduction (magnetic resonance imaging proton density fat fraction), NASH resolution without worsening fibrosis and fibrosis improvement. Risk of bias (RoB) was assessed using the Cochrane RoB 2.0 tool. Results: Three RCTs involving 2231 participants were included in the study. Resmetirom significantly reduced hepatic fat content (standardized mean differences − 4.61; 95% confidence interval [CI] −6.77, −2.44), increased NASH resolution without worsening fibrosis (risk ratio [RR] 2.51; 95% CI 1.74, 3.64), and improved fibrosis (RR 2.31; 95% CI 1.20, 4.44). Significant improvements in lipid parameters (low-density lipoprotein cholesterol, triglycerides, apolipoprotein-B, lipoprotein A) and liver enzymes (alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transpeptidase) were noted. Treatment-emergent adverse events were slightly higher in the resmetirom group (RR 1.04; 95% CI 1.01, 1.07), primarily mild gastrointestinal symptoms. Conclusion: Resmetirom effectively improves hepatic steatosis, histological features and metabolic parameters in NAFLD/NASH with an acceptable safety profile. Further long-term RCTs are needed to establish its impact on fibrosis regression and cardiovascular outcomes.