“ 在改善MASH而不恶化纤维化方面，Survodutide优于安慰剂，值得在3期试验中进一步研究。”
胰高血糖素受体和胰高血糖素样肽-1 (GLP-1)受体的双重激动作用可能比单独GLP-1受体激动作用治疗代谢功能障碍相关性脂肪性肝炎(MASH)更有效。
Survodutide(胰高血糖素受体和GLP-1受体的双重激动剂)在MASH和肝纤维化患者中的疗效和安全性尚不清楚。
很多人会问：药效怎样？
为了探究实际情况，研究人员进行了临床试验。
研究结果发表在医学四大頂刊之一NEJM（2023年影响因子96.2）。
*详细数据可点击左下角“阅读原文”
先直接上“答案”：
在改善MASH而不恶化纤维化方面，Survodutide优于安慰剂，值得在3期试验中进一步研究。
再看看研究怎么做的：
在这项为期48周的2期试验中，以1:1:1:1的比例随机分配活检证实的MASH和纤维化F1至F3期的成年人，接受每周一次的皮下注射，剂量为2.4、4.8或6.0 mg或安慰剂。
该试验分为两个阶段:24周的快速剂量递增阶段，随后是24周的维持阶段。
主要终点是MASH的组织学改善(减少)，无纤维化恶化。
次要终点包括肝脏脂肪含量减少至少30%，活检评估的纤维化改善(减少)至少一个阶段。
温馨提示：节录了部分肥胖数据，低体重的数据可参考原文；翻译难免有错漏，请以原文为准！
再看看结果：
共有293名随机分配的参与者接受了至少一剂的Survodutide或安慰剂。
与安慰剂组14%的参与者相比，2.4 mg组47%的参与者，4.8 mg组62%的参与者和6.0 mg组43%的参与者出现了MASH改善，没有纤维化恶化(二次剂量反应曲线作为最佳拟合模型P<0.001)。
在2.4 mg组中，63%的参与者的肝脏脂肪含量下降了至少30%，4.8 mg组为67%，6.0 mg组为57%，安慰剂组为14%;纤维化改善至少一个阶段的比例分别为34%、36%、34%和22%。
Survodutide组比安慰剂组更常见的不良事件包括恶心(66%对23%)、腹泻(49%对23%)和呕吐(41%对4%);严重不良事件发生在8%的生存组和7%的安慰剂组。
小编：效果还真的挺好啊！
A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis.
附：英文摘要
Abstract
Background:
Dual agonism of glucagon receptor and glucagon-like peptide-1 (GLP-1) receptor may be more effective than GLP-1 receptor agonism alone for treating metabolic dysfunction-associated steatohepatitis (MASH). The efficacy and safety of survodutide (a dual agonist of glucagon receptor and GLP-1 receptor) in persons with MASH and liver fibrosis are unclear.
Methods:
In this 48-week, phase 2 trial, we randomly assigned adults with biopsy-confirmed MASH and fibrosis stage F1 through F3 in a 1:1:1:1 ratio to receive once-weekly subcutaneous injections of survodutide at a dose of 2.4, 4.8, or 6.0 mg or placebo. The trial had two phases: a 24-week rapid-dose-escalation phase, followed by a 24-week maintenance phase. The primary end point was histologic improvement (reduction) in MASH with no worsening of fibrosis. Secondary end points included a decrease in liver fat content by at least 30% and biopsy-assessed improvement (reduction) in fibrosis by at least one stage.
Results:
A total of 293 randomly assigned participants received at least one dose of survodutide or placebo. Improvement in MASH with no worsening of fibrosis occurred in 47% of the participants in the survodutide 2.4-mg group, 62% of those in the 4.8-mg group, and 43% of those in the 6.0-mg group, as compared with 14% of those in the placebo group (P<0.001 for the quadratic dose-response curve as best-fitting model). A decrease in liver fat content by at least 30% occurred in 63% of the participants in the survodutide 2.4-mg group, 67% of those in the 4.8-mg group, 57% of those in the 6.0-mg group, and 14% of those in the placebo group; improvement in fibrosis by at least one stage occurred in 34%, 36%, 34%, and 22%, respectively. Adverse events that were more frequent with survodutide than with placebo included nausea (66% vs. 23%), diarrhea (49% vs. 23%), and vomiting (41% vs. 4%); serious adverse events occurred in 8% with survodutide and 7% with placebo.
Conclusions:
Survodutide was superior to placebo with respect to improvement in MASH without worsening of fibrosis, warranting further investigation in phase 3 trials. (Funded by Boehringer Ingelheim; 1404-0043 ClinicalTrials.gov number, NCT04771273; EudraCT number, 2020-002723-11.).
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参考文献：Sanyal AJ, Bedossa P, Fraessdorf M, Neff GW, Lawitz E, Bugianesi E, Anstee QM, Hussain SA, Newsome PN, Ratziu V, Hosseini-Tabatabaei A, Schattenberg JM, Noureddin M, Alkhouri N, Younes R; 1404-0043 Trial Investigators. A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis. N Engl J Med. 2024 Jul 25;391(4):311-319. doi: 10.1056/NEJMoa2401755. Epub 2024 Jun 7. PMID: 38847460.
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