Safety and efficacy of resmetirom in metabolic dysfunction-associated steatohepatitis (MASH): a systematic review and meta-analysis

Metabolic dysfunction-associated steatohepatitis (MASH) affects nearly 38% of the population, potentially progressing to cirrhosis and cancer. Lifestyle changes remain the cornerstone of management, but adherence is challenging, prompting the exploration of therapeutic options. Resmetirom, targeting thyroid hormone receptors, regulates liver enzymes and fat metabolism, showing potential as a treatment for MASH. This systematic review and meta-analysis evaluates the safety of resmetirom in MASH patients. Three randomized controlled trials with adult participants were analyzed, sourced from PubMed and the Cochrane Library until April 2024. Participants received either resmetirom or placebo, and data on adverse effects and efficacy outcomes were extracted. Statistical analyses, including risk ratios (RRs) and confidence intervals (CI), were performed using Review Manager (version 5.4.1) with a random-effects model. The pooled RR for serious adverse events was 0.85 (95% CI: 0.63-1.14; P = 0.28), indicating no significant difference. However, diarrhea (RR = 1.82, 95% CI: 1.41-2.35; P < 0.001) and nausea (RR = 1.73, 95% CI: 1.31-2.28; P < 0.001) showed higher incidence. No significant differences were found for fatigue (RR = 1.19, 95% CI: 0.77-1.84; P = 0.43) or urinary tract infections (RR = 1.07, 95% CI: 0.76-1.52; P = 0.69). Liver fat content, lipid profiles, and liver enzymes also showed significant improvement in the resmetirom group. Low heterogeneity across most outcomes indicated consistent findings among the studies. While resmetirom demonstrates efficacy in improving lipid and liver profiles, its increased risk of diarrhea and nausea should be considered in therapeutic decisions.