A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis
A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis
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DOI：
10.1056/nejmoa2028395
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发表时间：
2021-03-25
影响因子：
158.5
通讯作者：
Harrison, Stephen A.
中科院分区：
文献类型：
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作者：
Newsome, Philip N.;Buchholtz, Kristine;Harrison, Stephen A.
背景非酒精性脂肪性肝炎（NASH）是一种常见疾病，与发病率和死亡率增加相关，但治疗选择有限。胰高血糖素样肽 1 受体激动剂索马鲁肽对 NASH 患者的疗效和安全性尚不清楚。方法我们进行了一项为期 72 周的双盲 2 期试验，受试者为活检确诊为 NASH 且肝纤维化为 F1、F2 或 F3 期的患者。患者按照 3:3:3:1:1:1 的比例被随机分配接受每日一次皮下注射索马鲁肽（剂量为 0.1、0.2 或 0.4 mg）或相应的安慰剂。主要终点是 NASH 消退且纤维化未恶化。验证性次要终点是至少一个纤维化阶段的改善且 NASH 没有恶化。这些终点的分析仅在 F2 或 F3 期纤维化患者中进行；结果总共 320 名患者（其中 230 名患有 F2 或 F3 期纤维化）被随机分配接受索马鲁肽剂量为 0.1 mg（80 名患者）、0.2 mg（78 名患者）或 0.4 mg（82 名患者）或接受安慰剂（80 名患者）。 0.1 mg 组中 NASH 得到缓解且纤维化未恶化的患者比例为 40%，0.2 mg 组为 36%，0.4 mg 组为 59%，安慰剂组为 17%（P
BACKGROUNDNonalcoholic steatohepatitis (NASH) is a common disease that is associated with increased morbidity and mortality, but treatment options are limited. The efficacy and safety of the glucagon-like peptide-1 receptor agonist semaglutide in patients with NASH is not known.METHODSWe conducted a 72-week, double-blind phase 2 trial involving patients with biopsyconfirmed NASH and liver fibrosis of stage F1, F2, or F3. Patients were randomly assigned, in a 3:3:3:1:1:1 ratio, to receive once-daily subcutaneous semaglutide at a dose of 0.1, 0.2, or 0.4 mg or corresponding placebo. The primary end point was resolution of NASH with no worsening of fibrosis. The confirmatory secondary end point was an improvement of at least one fibrosis stage with no worsening of NASH. The analyses of these end points were performed only in patients with stage F2 or F3 fibrosis; other analyses were performed in all the patients.RESULTSIn total, 320 patients (of whom 230 had stage F2 or F3 fibrosis) were randomly assigned to receive semaglutide at a dose of 0.1 mg (80 patients), 0.2 mg (78 patients), or 0.4 mg (82 patients) or to receive placebo (80 patients). The percentage of patients in whom NASH resolution was achieved with no worsening of fibrosis was 40% in the 0.1-mg group, 36% in the 0.2-mg group, 59% in the 0.4-mg group, and 17% in the placebo group (P