A new liver-targeted agonist of thyroid hormone receptor beta resmetirom in treating MASLD/MASH: From mechanism to therapy.

Resmetirom is an oral, liver-targeted medication that selectively activates the thyroid hormone receptor beta (THRB) and thereby targets multiple pathophysiological mechanisms of metabolic dysfunction-associated steatohepatitis (MASH). By activating hepatic THRB, resmetirom promotes fatty acid oxidation, improves mitochondrial function, inhibits de novo lipogenesis and prevents hepatic cell injury and death in cultured cells, liver organoids and mice. Pivotal clinical trials have confirmed that resmetirom markedly reduces liver fat content, ameliorates inflammatory injury, and reverses liver fibrosis while also effectively lowering atherogenic lipid levels. The medication has a favorable safety and tolerability profile. Based on these findings, resmetirom was approved by the US Food and Drug Administration (FDA) in 2024 and by the European Union in August 2025. Further directions in this field will pivot on investigating the cardiovascular benefits of resmetirom, exploring its use in combination with other drugs, and the elucidation of its underlying molecular mechanism networks. This article reviews the pharmacological and clinical evidence regarding the treatment of MASH with resmetirom published by April 2026, with the aim to expanding the pharmacological profile of resmetirom and promoting the development of THRB agonism-based anti-MASH pharmacotherapies.