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在MASH和纤维化中进行Survodutide的第二阶段随机试验
Arun J Sanyal1, Pierre Bedossa1, Mandy Fraessdorf1
1From the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, Virginia Commonwealth University School of Medicine, Richmond (A.J.S.); Liverpat and University of Paris (P.B.), and Sorbonne Université, Institute for Cardiometabolism and Nutrition, Assistance Publique-Hôpitaux de Paris, INSERM Unité Mixte de Recherche Scientifique 1138, Centre de Recherche des Cordeliers (V.R.) - all in Paris; Boehringer Ingelheim, Ingelheim am Rhein (M.F., S.A.H and R.Y.), Saarland University Medical Center, Homburg (J.M.S.), and University of the Saarland, Saarbrücken (J.M.S.) - all in Germany; Covenant Metabolic Specialists, Sarasota, FL (G.W.N.); Houston Methodist Hospital and Houston Research Institute, Houston (M.N.), and the Texas Liver Institute, University of Texas Health San Antonio, San Antonio (E.L. and N.A.) - all in Texas; the University of Turin, Turin, Italy (E.B.); the Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, and Newcastle National Institute for Health and Care Research Biomedical Research Centre, Newcastle upon Tyne Hospitals National Health Service (NHS) Foundation Trust, Newcastle upon Tyne (Q.M.A.), the University Hospitals Birmingham NHS Foundation Trust and the University of Birmingham, Birmingham (P.N.N.), and the Institute of Hepatology, Faculty of Life Sciences and Medicine, King's College London and King's College Hospital, London (P.N.N.) - all in the United Kingdom; Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT (A.H.-T.); and Arizona Liver Health, Chandler (N.A.).
在第二阶段试验中,双重葡萄糖和GLP-1受体激动剂Survodutide显著改善了与代谢功能障碍相关的脂肪肝炎 (MASH),而没有使纤维化恶化. 需要进一步的第三阶段研究来证实MASH治疗的这些有希望的结果.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 内分泌学 在内分泌学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 与代谢功能障碍相关的脂肪肝炎 (MASH) 构成了严重的健康负担.
- 针对葡萄糖受体和葡萄糖样-1 (GLP-1) 受体的双重激动性显示了MASH治疗的潜力.
- 在肝纤维化MASH中,双重葡萄糖和GLP-1受体激动剂survodutide的疗效需要进行研究.
研究的目的:
- 评估Survodutide在活检确认的MASH和肝纤维化 (F1-F3阶段) 患者的疗效和安全性.
- 为了评估survodutide对组织学MASH改善和肝纤维化的影响.
- 为了确定MASH治疗中最优的苏尔沃杜提德剂量.
主要方法:
- 一项为期48周的随机,双盲,安慰剂控制的第二阶段试验,涉及293名患有MASH和纤维化的人.
- 参与者每周接受皮下注射苏尔沃杜提德 (2.4毫克,4.8毫克或6.0毫克) 或安慰剂.
- 主要终点:在MASH没有纤维化恶化的组织学改善;次要终点:减少肝脂肪和纤维化改善.
主要成果:
- 在47% (2.4毫克),62% (4.8毫克) 和43% (6.0毫克) 的survodutide接受者中,没有纤维化恶化的情况下,观察到组织学MASH的改善,而安慰剂 (P<0.001) 则为14%.
- 与安慰剂相比,在survodutide剂量组中,肝脏脂肪含量显著降低,肝纤维化有所改善.
- 恶心,腹和吐等不良事件更频繁地发生在survodutide中,但严重的不良事件与安慰剂相似.
结论:
- 与安慰剂相比,Survodutide在改善MASH而不会恶化纤维化方面表现出更高的疗效.
- 这些结果支持在更大规模的MASH治疗3期试验中进一步调查survodutide.
- 苏尔沃杜提德代表了患有MASH和肝纤维化患者的潜在治疗选择.
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