Resmetirom in the Treatment of Noncirrhotic Non-Alcoholic Steatohepatitis: An In-Depth Review

Abstract

Background: Non-alcoholic steatohepatitis (NASH) is emerging as a significant global health challenge, closely linked to obesity and metabolic disorders. Despite its increasing prevalence, effective pharmacotherapy remains limited. Resmetirom, a selective thyroid hormone receptor beta agonist, offers a promising therapeutic approach for NASH, particularly in patients with moderate to advanced liver fibrosis. Aims: This review aims to comprehensively evaluate resmetirom for its therapeutic efficacy and safety in treating non-alcoholic steatohepatitis (NASH), a severe stage of non-alcoholic fatty liver disease (NAFLD) with a growing global prevalence. Study Design: A narrative literature review was conducted, focusing on the pharmacokinetics, pharmacodynamics, clinical efficacy, and safety of resmetirom in treating NASH. Methodology: A systematic search was performed across databases, including PubMed and Google Scholar, for English-language articles published between 2010 and 2024. Keywords used included "resmetirom," "thyroid hormone receptor beta agonist," "NASH treatment," and related terms. Articles discussing pharmacology, clinical efficacy, and safety evidence of resmetirom were included. Studies on cost-effectiveness or non-safety-related aspects, non-English articles, or those lacking full-text accessibility were excluded. Results: Resmetirom, a liver-directed thyroid hormone receptor beta (THR-β) selective agonist, demonstrated significant efficacy in reducing liver fat content, improving liver histology, and reducing LDL cholesterol levels. Phase 3 trials showed improvements in fibrosis without worsening the NAFLD Activity Score. Adverse events were mostly mild to moderate, with gastrointestinal issues like diarrhea and nausea being the most common. Resmetirom exhibited a favourable safety profile, with no systemic hyperthyroidism or hypothyroidism observed. However, careful consideration is needed for drug interactions and specific patient populations. Conclusion: Resmetirom represents a significant advancement in NASH treatment, offering a targeted approach that minimizes systemic thyroid-related side effects. It is the first FDA-approved medication for NASH, showing promise in reducing liver fat and improving histology and metabolic parameters. Further long-term studies are necessary to fully understand its durability and impact on clinical outcomes. Resmetirom provides a promising new option for managing NASH, particularly for patients with moderate to advanced fibrosis.