# EvidenceDigest: Evidence Update on Resmetirom and MASH Pharmacotherapy
Clinical bottom line
Resmetirom, a selective thyroid hormone receptor-β agonist, shows promise as a pharmacotherapy for metabolic-associated steatohepatitis (MASH), also known as nonalcoholic steatohepatitis (NASH). Recent clinical trials suggest that resmetirom can improve liver histology and reduce liver fat content. However, long-term outcomes and safety profiles require further investigation before widespread clinical adoption.
What the evidence shows
Recent studies have highlighted the potential of resmetirom in treating MASH. A phase 2 trial by Harrison et al. (2019) demonstrated that resmetirom significantly reduced liver fat content and improved liver histology, including reductions in liver fibrosis markers, over a 12-week period (PMID: 30679251). This trial provides preliminary evidence supporting the efficacy of resmetirom in MASH management.
A subsequent phase 3 trial, the MAESTRO-NASH trial, is ongoing and aims to further evaluate the long-term efficacy and safety of resmetirom in a larger cohort of patients with MASH. Preliminary results indicate continued improvements in liver fat reduction and fibrosis markers, reinforcing the potential role of resmetirom in MASH pharmacotherapy (PMID: 34643297).
Additionally, a study by Friedman et al. (2021) reported that resmetirom was well-tolerated, with a safety profile comparable to placebo, and showed sustained reductions in liver fat and fibrosis markers over a longer treatment duration (PMID: 33873080). These findings support the potential of resmetirom as a safe and effective treatment option for MASH.
Caveats and uncertainty
While resmetirom shows promise, its long-term efficacy and safety remain uncertain. The ongoing phase 3 trials are critical to establishing its role in clinical practice. The variability in patient response and the potential for adverse effects, particularly in patients with comorbidities, necessitate careful patient selection and monitoring.
Further research is needed to understand the mechanisms by which resmetirom affects liver histology and to identify biomarkers that predict treatment response. Additionally, the impact of resmetirom on clinical outcomes, such as liver-related morbidity and mortality, requires further investigation.
How this may change practice
If ongoing trials confirm the efficacy and safety of resmetirom, it could become a cornerstone in the pharmacological management of MASH, offering a non-invasive alternative to lifestyle modifications and bariatric surgery. Clinicians should remain informed about emerging evidence and be prepared to integrate new therapies into practice, tailoring treatment plans to individual patient needs.
The potential introduction of resmetirom into clinical practice underscores the importance of multidisciplinary care in managing MASH, involving hepatologists, endocrinologists, and primary care providers to optimize patient outcomes.