Resmetirom: A New FDA-approved Drug as a Targeted Therapeutic Strategy in Metabolic Dysfunction Associated Steatohepatitis: Translational Evidence from Current Clinical Trials.

Abstract

Metabolic dysfunction-associated steatohepatitis (MASH) represents a significant global health burden, affecting 3-5% of the population and projected to become a leading cause of liver transplantation by 2030. This review examines Resmetirom, the first FDA-approved drug for non-cirrhotic MASH with moderate to severe hepatic fibrosis. As a selective thyroid hormone receptor beta (THR-β) agonist, Resmetirom enhances hepatic lipid metabolism through increased mitochondrial β-oxidation and improved lipoprotein profiles. Multiple clinical trials have demonstrated its efficacy in reducing hepatic fat content, improving liver histology, and resolving MASH without worsening fibrosis. While generally well-tolerated, gastrointestinal side effects including diarrhea and nausea were more common with Resmetirom than placebo. This breakthrough therapy offers a promising option for MASH management, though long-term studies and broader geographic representation in trials remain necessary to fully establish its role in clinical practice.