Efficacy and safety of resmetirom in MASLD and MASH: network meta-analysis of randomized clinical trials.

introductionMetabolic-Associated Steatohepatitis-Related Liver Disease (MASLD) and, its progressive form, Metabolic-Associated Steatohepatitis (MASH) pose significant global health challenges. Current therapeutic strategies targeting metabolic abnormalities have shown promise but lack specificity for the liver. Thyroid hormones, particularly thyroid hormone receptor beta (THR-β) agonists like resmetirom, offer a targeted approach to liver-related pathways. CONTENT: A network meta-analysis (NMA) comparing different doses of resmetirom to placebo for MASLD and MASH was conducted. PubMed, Scopus, Cochrane, and Web of Science were searched for relevant randomized controlled trials (RCTs). Efficacy outcomes included histological, radiological, and biochemical parameters, while safety outcomes comprised adverse events and treatment discontinuation. SUMMARY: Resmetirom demonstrated dose-dependent efficacy in histological and radiological assessments, with the 100 mg dose showing superior MASH resolution and hepatic fat reduction. Biochemical markers indicated improved liver function with resmetirom treatment. However, adverse events, particularly diarrhea and nausea, were more prevalent in the resmetirom group, leading to higher treatment discontinuation rates. OUTLOOK: Resmetirom shows promise as a therapeutic option for MASLD and MASH management, with significant improvements in liver health parameters. However, safety concerns warrant careful monitoring in clinical practice. Further research is needed to optimize its long-term safety and efficacy.