NEJM:GLP-1受体激动剂治疗非酒精性脂肪性肝炎(NASH):脂肪变性和肝损伤显著减轻,但纤维化改善不明显

2020-11-18 MedSci原创 MedSci原创

Semaglutide治疗组NASH缓解比率显着高于安慰剂组(40.4%比17.2%)。

在美国肝病研究协会(AASLD)年会The liver meeting会议上,诺和诺德(Novo Nordisk)汇报了其GLP-1受体激动剂Semaglutide的阳性结果,Semaglutide显著减轻了非酒精性脂肪性肝炎(NASH)患者的肝脏脂肪变性和肝损伤,但并未显著改善纤维化严重程度。相关研究结果也于2020年11月13日发表在NEJM杂志上。

在临床研究中,将320例确诊NASH患者随机接受皮下注射semaglutide 0.1 mg(n = 57)、0.2 mg(n = 59)、0.4 mg(n = 56)或安慰剂(n = 58),每天一次,持续72周。在这些患者中,女性占61%,2型糖尿病占62%,纤维化F1期占28%,纤维化F2期占23%,纤维化F3期占49%,平均NAFLD活性评分(NAS)为4.9。

结果显示Semaglutide治疗230名患者,达到了NASH缓解的主要终点,使用Semaglutide(所有剂量组)的缓解比率显着高于安慰剂组(40.4%比17.2%)。其中semaglutide 0.2 mg组的比例为35.6%,0.4 mg组的比例为58.9%。对于纤维化阶段改善的次要终点,0.1 mg组改善比率为49.1%,0.2 mg组改善比率为32.2%,0.4 mg组改善比率为42.9%,而安慰剂组为32.8%。与安慰剂相比,Semaglutide组无显著差异。

但是随着Semaglutide剂量的增加,纤维化疾病发生进展的患者比例下降,0.1 mg组为10.0%,0.2 mg组为7.7%,0.4 mg组为4.9%,而安慰剂组为18.8% 。并且与安慰剂相比,Semaglutide呈现剂量依赖性地降低谷丙转氨酶和谷草转氨酶的水平。

塞马鲁肽显示的安全性与其在其他适应症中一致,没有新的安全问题。最常见的不良反应是胃肠道疾病,包括恶心,便秘,呕吐和腹痛。

原始出处:

1. A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis. N Engl J Med. 2020 Nov 13.

2. https://www.firstwordpharma.com/node/1775177?tsid=4

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    2021-08-07 医海拾贝

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    0

  4. 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encryptionId=70f484349b5, topicName=脂肪性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c49e75, createdName=qjddjq, createdTime=Tue Dec 29 01:30:30 CST 2020, time=2020-12-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1673632, encodeId=cecd16e3632a5, content=<a href='/topic/show?id=757b954e922' target=_blank style='color:#2F92EE;'>#酒精性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=95479, encryptionId=757b954e922, topicName=酒精性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=398f26933958, createdName=huiwelcome, createdTime=Sun May 16 03:30:30 CST 2021, time=2021-05-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1991219, encodeId=f9fd19912192c, content=<a href='/topic/show?id=7b0299e238b' target=_blank style='color:#2F92EE;'>#非酒精性脂肪性肝炎(NASH)#</a>, beContent=null, 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encodeId=f54b90518986, content=好, beContent=null, objectType=article, channel=null, level=null, likeNumber=95, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/PiajxSqBRaEIrIoKA6ro6CRnrVdQgZeVHMNOp9zBGDa4zbuUVatOhpScaygqRnJWeibItibcFFETwq4g7Q9z1LbGA/0, createdBy=81822151800, createdName=黛绿年华, createdTime=Sat Dec 05 15:08:40 CST 2020, time=2020-12-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1398066, encodeId=47501398066b5, content=<a href='/topic/show?id=8bee565436d' target=_blank style='color:#2F92EE;'>#损伤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=56543, encryptionId=8bee565436d, topicName=损伤)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eoNX3lUOlDKGBUEPNwZx0nibmdcFyeibnX4WMhUSCU2REpGRWtSmnT2CCs0dA5waxvJknYDxwtYnIcQ/132, createdBy=294e2500218, createdName=ms3046638856685384, createdTime=Fri Nov 20 01:30:30 CST 2020, time=2020-11-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1627840, encodeId=64f0162e84042, content=<a href='/topic/show?id=ab4f66e8913' target=_blank style='color:#2F92EE;'>#激动剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66789, encryptionId=ab4f66e8913, topicName=激动剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=95bc21134754, createdName=medscijoin, createdTime=Fri Nov 20 01:30:30 CST 2020, time=2020-11-20, status=1, ipAttribution=)]
    2020-12-29 qjddjq
  5. 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encryptionId=70f484349b5, topicName=脂肪性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c49e75, createdName=qjddjq, createdTime=Tue Dec 29 01:30:30 CST 2020, time=2020-12-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1673632, encodeId=cecd16e3632a5, content=<a href='/topic/show?id=757b954e922' target=_blank style='color:#2F92EE;'>#酒精性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=95479, encryptionId=757b954e922, topicName=酒精性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=398f26933958, createdName=huiwelcome, createdTime=Sun May 16 03:30:30 CST 2021, time=2021-05-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1991219, encodeId=f9fd19912192c, content=<a href='/topic/show?id=7b0299e238b' target=_blank style='color:#2F92EE;'>#非酒精性脂肪性肝炎(NASH)#</a>, beContent=null, 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encodeId=f54b90518986, content=好, beContent=null, objectType=article, channel=null, level=null, likeNumber=95, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/PiajxSqBRaEIrIoKA6ro6CRnrVdQgZeVHMNOp9zBGDa4zbuUVatOhpScaygqRnJWeibItibcFFETwq4g7Q9z1LbGA/0, createdBy=81822151800, createdName=黛绿年华, createdTime=Sat Dec 05 15:08:40 CST 2020, time=2020-12-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1398066, encodeId=47501398066b5, content=<a href='/topic/show?id=8bee565436d' target=_blank style='color:#2F92EE;'>#损伤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=56543, encryptionId=8bee565436d, topicName=损伤)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eoNX3lUOlDKGBUEPNwZx0nibmdcFyeibnX4WMhUSCU2REpGRWtSmnT2CCs0dA5waxvJknYDxwtYnIcQ/132, createdBy=294e2500218, createdName=ms3046638856685384, createdTime=Fri Nov 20 01:30:30 CST 2020, time=2020-11-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1627840, encodeId=64f0162e84042, content=<a href='/topic/show?id=ab4f66e8913' target=_blank style='color:#2F92EE;'>#激动剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66789, encryptionId=ab4f66e8913, topicName=激动剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=95bc21134754, createdName=medscijoin, createdTime=Fri Nov 20 01:30:30 CST 2020, time=2020-11-20, status=1, ipAttribution=)]
  6. 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  7. 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  8. 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createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eoNX3lUOlDKGBUEPNwZx0nibmdcFyeibnX4WMhUSCU2REpGRWtSmnT2CCs0dA5waxvJknYDxwtYnIcQ/132, createdBy=294e2500218, createdName=ms3046638856685384, createdTime=Fri Nov 20 01:30:30 CST 2020, time=2020-11-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1627840, encodeId=64f0162e84042, content=<a href='/topic/show?id=ab4f66e8913' target=_blank style='color:#2F92EE;'>#激动剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66789, encryptionId=ab4f66e8913, topicName=激动剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=95bc21134754, createdName=medscijoin, createdTime=Fri Nov 20 01:30:30 CST 2020, time=2020-11-20, status=1, ipAttribution=)]
    2020-12-05 黛绿年华

    0

  9. 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  10. 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