Review Maps Pharmacological Therapies for MASLD/MASH, Spotlighting Resmetirom, Semaglutide, and Incretin-Based Agents

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease globally, progressing to metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis, and hepatocellular carcinoma. Despite weight loss being foundational, achieving it through lifestyle changes is challenging for many patients, creating a critical need for effective pharmacological interventions. Current standard-of-care often falls short in preventing disease progression, especially to advanced fibrosis or cirrhosis. This gap highlights the importance of understanding novel and emerging therapies that target the underlying metabolic dysfunction.

This narrative review synthesizes the current pharmacological landscape for MASLD, including agents with conditional approval for MASH. Researchers summarized the efficacy and mechanisms of action for established therapies like resmetirom (a selective thyroid hormone receptor-β agonist) and semaglutide (a glucagon-like peptide-1 receptor agonist). The review also explored emerging incretin-based therapies and fibroblast growth factor-21 analogues, alongside current guidance on non-invasive tests for treatment selection and monitoring. The scope included recent advancements in obesity and metabolic medicine, framing MASLD management within a complication-centric obesity paradigm.

The review identified resmetirom and semaglutide as two conditionally approved pharmacological agents for MASH, representing significant advancements in the field. Resmetirom, acting as a liver-directed, selective thyroid hormone receptor-β agonist, targets hepatic metabolism directly. Semaglutide, a GLP-1 receptor agonist, leverages its broader metabolic effects, including weight loss and glycemic control, to improve liver outcomes. Beyond these agents, the review highlighted the promise of emerging incretin-based therapies (e.g., dual GLP-1/GIP agonists) and fibroblast growth factor-21 analogues, which are under investigation for their potential to address various facets of MASLD pathogenesis. The authors also detailed how non-invasive tests can guide treatment selection and monitor response, integrating these tools into a more personalized approach. This evolving paradigm shifts towards complication-centric obesity management, positioning incretin-based therapies as a potential backbone for managing obesity and its related conditions, including MASLD. > The review underscores that despite these recent approvals, effective pharmacological therapy for MASH-related cirrhosis remains an unmet need, emphasizing the critical importance of early identification and intervention.