Metabolic dysfunction-associated steatohepatitis treatment: spotlight on the latest hepatoprotective drugs

Expert Opin Pharmacother. 2025 Oct-Oct;26(14-15):1589-1598. doi: 10.1080/14656566.2025.2566258. Epub 2025 Sep 25.

Abstract

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) has become a major public health concern. Recently, the development of liver-targeted pharmacologic therapies has gained momentum, culminating in the conditional approval of resmetirom which has generated renewed optimism for the management of MASLD. In addition, several other investigational agents have shown promising results in clinical trials.

Areas covered: In this review, we summarize the data on recent pharmacologic developments in the treatment of MASLD, with a particular focus on agents targeting the more progressive form - at-risk metabolic dysfunction-associated steatohepatitis (MASH). These therapies act through a variety of direct and indirect pathways within the liver.

Expert opinion: The approval of liver-targeted therapies for MASH marks the beginning of a new era in disease management, offering promising outcomes even for advanced stages such as cirrhosis. The rising prevalence of obesity and T2DM suggests that new treatment options that can treat multiple comorbidities - including GLP1 receptor agonists, dual, and multi-agonists - are likely to play a significant role in the management of MASH. The availability of effective pharmacologic treatment options highlights the need for effective screening strategies in high-risk populations and call for the engagement of policymakers to develop coordinated plans at a global level.

Keywords: Fibrosis; GLP-1 receptor agonist; MASH; MASLD; resmetirom.

Publication types

  • Review

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy
  • Drug Development
  • Fatty Liver* / drug therapy
  • Fatty Liver* / etiology
  • Fatty Liver* / physiopathology
  • Humans
  • Metabolic Diseases* / complications
  • Metabolic Diseases* / drug therapy
  • Molecular Targeted Therapy
  • Non-alcoholic Fatty Liver Disease / drug therapy
  • Obesity / complications
  • Obesity / drug therapy
  • Protective Agents* / pharmacology
  • Protective Agents* / therapeutic use

Substances

  • Protective Agents