Department of Endocrinology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, 576104, India.
Department of Endocrinology and Metabolism, Lancashire Teaching Hospitals NHS Trust, Preston, PR2 9HT, United Kingdom.
Sci Rep. 2024 Aug 26;14(1):19790. doi: 10.1038/s41598-024-70242-8.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is an important public health problem owing to its high prevalence and associated morbidity and mortality secondary to progressive liver disease and cardiovascular events. Resmetirom, a selective thyroid hormone receptor-β agonist has been developed as a therapeutic modality for MASLD. This systematic review and meta-analysis aimed to evaluate the effectiveness and safety of resmetirom compared to a placebo in the treatment of MASLD. Eligible studies were systematically identified by screening PubMed, Scopus, Web of Science, Cochrane library, Embase, and ClinicalTrials.gov from 2014 to 2024. Only randomized controlled trials comparing the efficacy and safety of resmetirom in the treatment of MASLD against placebo were included in the analysis. Meta-analysis was performed using RevMan 5.4 software. Four studies with low risk of bias and involving a total of 2359 participants were identified. The metanalysis included only three clinical trials with 2234 participants. A significant reduction in MRI-proton density fat fraction (MRI-PDFF) with 80 mg Resmetirom compared to that with placebo [SMD - 27.74 (95% CI - 32.05 to - 32.42), p < 0.00001] at 36-52 weeks as well as at 12-16 weeks [SMD - 30.92 (95% CI - 36.44 to - 25.40), p < 0.00001]. With Resmetirom 100 mg dose at 36-52 weeks [SMD - 36.05 (95% CI - 40.67 to - 31.43), p < 0.00001] and 12-16 weeks [SMD - 36.89 (95% CI - 40.73 to - 33.05), p < 0.00001] were observed. Resmetirom treatment was associated with a significant reduction in LDL-c triglyceride, lipoproteins. and liver enzymes. There was significant reduction FT4 and increase in SHBG and sex steroids with Resmetirom compared to placebo. There was no major difference in the overall treatment emergent adverse events at 80 mg [OR 1.55 (95% CI 0.84 to 2.87), and 100 mg [OR 1.13 (95% CI 0.78 to 1.63), doses of Resmetirom compared to placebo. However, gastrointestinal adverse events diarrhoea and nausea occurred in ≥ 10% in the Resmetirom group compared to placebo at < 12 week. Resmetirom treatment showed modest efficacy in treating MASLD with reduction in MRI-PDFF, LDL-c, triglyceride, lipoproteins, liver enzymes and NASH biomarkers without significant safety concerns. Larger and long-term RCTs may further confirm this promising outcomes of Resmetirom use in MASLD.
代谢功能障碍相关脂肪性肝病 (MASLD) 是一个重要的公共卫生问题，因为其高患病率以及与进行性肝病和心血管事件相关的发病率和死亡率。Resmetirom 是一种选择性甲状腺激素受体-β激动剂，已被开发为治疗 MASLD 的一种治疗方法。本系统评价和荟萃分析旨在评估 Resmetirom 与安慰剂相比在治疗 MASLD 中的疗效和安全性。通过筛选 PubMed、Scopus、Web of Science、Cochrane 图书馆、Embase 和 ClinicalTrials.gov，从 2014 年到 2024 年，系统地确定了符合条件的研究。仅纳入了比较 Resmetirom 与安慰剂治疗 MASLD 的疗效和安全性的随机对照试验进行分析。使用 RevMan 5.4 软件进行荟萃分析。确定了四项低偏倚风险的研究，共涉及 2359 名参与者。荟萃分析仅纳入了三项涉及 2234 名参与者的临床试验。与安慰剂相比，Resmetirom 80mg 治疗 36-52 周时 [SMD-27.74（95%CI-32.05 至-32.42），p<0.00001]，以及治疗 12-16 周时 [SMD-30.92（95%CI-36.44 至-25.40），p<0.00001]时 MRI 质子密度脂肪分数（MRI-PDFF）显著降低。Resmetirom 100mg 剂量治疗 36-52 周时 [SMD-36.05（95%CI-40.67 至-31.43），p<0.00001]和治疗 12-16 周时 [SMD-36.89（95%CI-40.73 至-33.05），p<0.00001]时也观察到了同样的结果。与安慰剂相比，Resmetirom 治疗可显著降低 LDL-c、甘油三酯、脂蛋白和肝脏酶。与安慰剂相比，Resmetirom 治疗后 FT4 降低，SHBG 和性激素增加。与安慰剂相比，Resmetirom 80mg [OR 1.55（95%CI 0.84 至 2.87）]和 100mg [OR 1.13（95%CI 0.78 至 1.63）]剂量的总治疗期间出现的不良事件发生率没有显著差异。然而，与安慰剂相比，Resmetirom 组在治疗 12 周内出现胃肠道不良事件腹泻和恶心的发生率≥10%。Resmetirom 治疗在治疗 MASLD 方面显示出适度的疗效，可降低 MRI-PDFF、LDL-c、甘油三酯、脂蛋白、肝脏酶和 NASH 生物标志物，且无明显安全性问题。更大规模和长期的 RCT 可能会进一步证实 Resmetirom 在 MASLD 中的应用具有良好的效果。
