Resmetirom: The First FDA-Approved Drug for Metabolic Dysfunction-Associated Steatohepatitis (MASH) with a Perspective on Precision Medicine.

Abstract

Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive form of metabolic dysfunction-associated steatotic liver disease (MASLD) involving hepatocyte destruction, inflammation, and typically pericellular fibrosis, potentially progressing to cirrhosis. Resmetirom, a T3 analogue and an oral agonist of thyroid hormone receptor-β(THR-β), represents a significant advancement in targeted drug therapy for MASH as the first US Food and Drug Administration (FDA)-approved treatment. Clinical trials have shown that resmetirom effectively improves MASH markers, reduces liver fat content, and exhibits high selectivity for THR-β, which is predominantly expressed in the liver. Despite promising research data, challenges remain in the treatment of MASH with resmetirom, including adverse reactions and limited efficacy in some patients. This article reviews the discovery, mechanisms, and clinical evaluation of resmetirom in detail, and discusses the challenges encountered in MASH precision therapy.