Resmetirom in Metabolic Dysfunction-Associated Steatohepatitis (MASH): A Systematic Review

Background: Previously known as nonalcoholic steatohepatitis (NASH), metabolic dysfunction-associated steatohepatitis (MASH) is a major global health concern that is strongly associated with metabolic syndrome, type 2 diabetes, and obesity. There are still not many therapeutic alternatives accessible, despite substantial research efforts. Because of its liver-selective properties and lipid-lowering benefits, Resmetirom (MGL-3196), a selective agonist of the thyroid hormone receptor-β (THR-β), has emerged as a viable therapeutic. The purpose of this review is to methodically assess and gather the available clinical data about the effectiveness and safety of resmetirom in people with MASH.

Methods: Using PubMed, Embase, ClinicalTrials.gov, and the Cochrane Library, a thorough systematic literature search was conducted comprehensively, encompassing data up to May 10, 2025. RCTs and observational studies that evaluated the impact of resmetirom on histological or biochemical improvement in MASH were included. The studies were assessed, pertinent data was retrieved, and the danger of bias was investigated by two independent reviewers. The data synthesis focused on adverse effects, alterations in lipid profiles, correction of liver enzymes, and histological responses.

Results: Six studies in all, including two observational studies and four RCTs, with 2,314 individuals with biopsy-confirmed MASH met the inclusion criteria. Resmetirom resolved NASH without aggravating fibrosis in as many as 26% of patients at 36 weeks, and it dramatically decreased liver fat content [Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF) drop of ≥30%]. It also led to significant reductions in triglycerides, ApoB, and LDL-C. The majority of the reported side effects were minor and included nausea, diarrhea, and brief elevations in liver enzymes. No significant adverse events or an increase in cardiovascular problems were seen.

Conclusion: In addition to having positive cardiometabolic effects, Resmetirom shows promising efficacy in reducing liver fat and improving important histological features of MASH. It is well acknowledged and has the potential to be the first medication to alter the course of MASH. To confirm these findings and assess long-term impacts, more thorough and prolonged research is required