AIM:GLP-1RAs治疗2型糖尿病—受益和损害

2015-12-08 catxa 译 MedSci原创

与其他每周一次GLP-1RAs相比,dulaglutide (1.5mg)、每周一次exenatide和taspoglutide(20mg)具有较大程度降低HbA1c、空腹血糖和体重的效果。Taspoglutide (20mg)使用者发生恶心的风险最高。每周一次GLP-1RAs类药物使用者发生低血糖的风险相似。

背景:每周一次GLP-1RAs(glucagon-like peptide-1 receptor agonists,GLP-1受体激动剂)是治疗2型糖尿病新药。

目的:总结2型糖尿病成年患者接受每周一次GLP-1RAs治疗代谢疾病的疗效和副作用的证据。

数据来源: 从开始到2015年9月26日,电子数据库(PubMed、Web of Science、Cochrane Central注册的对照试验,美国FDA,欧洲药品局,ClinicalTrials.gov)和会议摘要。

研究纳入标准:随机对照试验(随访≥24周),研究albiglutide、dulaglutide、每周一次exenatide、semaglutide和taspoglutide,报告代谢疾病【主要结局,HbA1c(糖化血红蛋白】或安全结局。

数据提取:两位研究人员单独提取数据,评估偏倚风险。没有应用语言限制。

数据综合:共纳入34项试验(21126名受试者)。

与安慰剂相比,每周一次GLP-1RAs降低HbA1c 和空腹血糖,taspoglutide (20mg)、每周一次exenatide、dulaglutide(1.5mg) 减少体重。

在每周一次GLP-1RAs中,dulaglutide (1.5 mg)和taspoglutide (10 mg)降低HbA1c程度最大(–0.4%,95%CI–0.7%- –0.2%),每周一次exenatide和albiglutide降低空腹血糖最明显(-0.7mmol/L,95%CI -1.1 - -0.2mmol/L),taspoglutide(20mg)、dulaglutide (0.75mg)减少体重最多(-1.5kg,95% CI -2.2 - -0.8)。
各组间血压、血脂和c反应蛋白水平临床上没有差异。

与albiglutide和dulaglutide相比,每周一次exenatide增加心率(1.4bpm-3.2bpm)在每周一次GLP-1RAs中,各种药物低血糖症风险相似,taspoglutide(20mg)组受试者发生恶心的风险最大(OR 1.9-5.9)。

研究限制: semaglutide数据不可用,结局的定义具有异质性,73%的试验使用 LOCF(Last observation carried forward,末次观测值结转),可能存在发表偏倚。

结论:与其他每周一次GLP-1RAs相比,dulaglutide (1.5mg)、每周一次exenatide和taspoglutide(20mg)具有较大程度降低HbA1c、空腹血糖和体重的效果。Taspoglutide (20mg)使用者发生恶心的风险最高。每周一次GLP-1RAs类药物使用者发生低血糖的风险相似。

原文出处:

Francesco Zaccardi, Zin Zin Htike, David R. Webb, et all. Benefits and Harms of Once-Weekly Glucagon-like Peptide-1 Receptor Agonist Treatments: A Systematic Review and Network Meta-analysis. Ann Intern Med. Published online 8 December 2015.

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    2016-03-08 360611848
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    2016-03-14 忠诚向上

    好好学习,继续研究

    0

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    2016-03-14 忠诚向上

    好好学习,继续研究

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=1658658, encodeId=dca8165865870, content=<a href='/topic/show?id=4b4d80e878' target=_blank style='color:#2F92EE;'>#GLP-1R#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8078, encryptionId=4b4d80e878, topicName=GLP-1R)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=fea024898996, createdName=360611848, createdTime=Tue Mar 08 18:55:00 CST 2016, time=2016-03-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=69274, encodeId=0b93692e416, content=好好学习,继续研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=88, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45101626056, createdName=忠诚向上, createdTime=Mon Mar 14 12:07:00 CST 2016, time=2016-03-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=69275, encodeId=2356692e542, content=好好学习,继续研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=92, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45101626056, createdName=忠诚向上, createdTime=Mon Mar 14 12:07:00 CST 2016, time=2016-03-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=69276, encodeId=c56a692e68f, content=好好学习,继续研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=101, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45101626056, createdName=忠诚向上, createdTime=Mon Mar 14 12:07:00 CST 2016, time=2016-03-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=69277, encodeId=9377692e731, content=好好学习,继续研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=118, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45101626056, createdName=忠诚向上, createdTime=Mon Mar 14 12:07:00 CST 2016, time=2016-03-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=69278, encodeId=f2b9692e849, content=好好学习,继续研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45101626056, createdName=忠诚向上, createdTime=Mon Mar 14 12:07:00 CST 2016, time=2016-03-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=69279, encodeId=41e3692e98b, content=好好学习,继续研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=109, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45101626056, createdName=忠诚向上, createdTime=Mon Mar 14 12:07:00 CST 2016, time=2016-03-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=69280, encodeId=408d6928035, content=好好学习,继续研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45101626056, createdName=忠诚向上, createdTime=Mon Mar 14 12:07:00 CST 2016, time=2016-03-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1422694, encodeId=0a021422694bf, content=<a href='/topic/show?id=54fa80e701' target=_blank style='color:#2F92EE;'>#GLP-1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8077, encryptionId=54fa80e701, topicName=GLP-1)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f8f23732777, createdName=yibei, createdTime=Thu Dec 10 10:55:00 CST 2015, time=2015-12-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1621998, encodeId=d80b162199826, content=<a href='/topic/show?id=392480e970' target=_blank style='color:#2F92EE;'>#GLP-1RA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8079, encryptionId=392480e970, topicName=GLP-1RA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f14520287581, createdName=bioon10, createdTime=Thu Dec 10 10:55:00 CST 2015, time=2015-12-10, status=1, ipAttribution=)]
    2016-03-14 忠诚向上

    好好学习,继续研究

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=1658658, encodeId=dca8165865870, content=<a href='/topic/show?id=4b4d80e878' target=_blank style='color:#2F92EE;'>#GLP-1R#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8078, encryptionId=4b4d80e878, topicName=GLP-1R)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=fea024898996, createdName=360611848, createdTime=Tue Mar 08 18:55:00 CST 2016, time=2016-03-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=69274, encodeId=0b93692e416, content=好好学习,继续研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=88, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45101626056, createdName=忠诚向上, createdTime=Mon Mar 14 12:07:00 CST 2016, time=2016-03-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=69275, encodeId=2356692e542, content=好好学习,继续研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=92, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45101626056, createdName=忠诚向上, createdTime=Mon Mar 14 12:07:00 CST 2016, time=2016-03-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=69276, encodeId=c56a692e68f, content=好好学习,继续研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=101, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45101626056, createdName=忠诚向上, createdTime=Mon Mar 14 12:07:00 CST 2016, time=2016-03-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=69277, encodeId=9377692e731, content=好好学习,继续研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=118, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45101626056, createdName=忠诚向上, createdTime=Mon Mar 14 12:07:00 CST 2016, time=2016-03-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=69278, encodeId=f2b9692e849, content=好好学习,继续研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45101626056, createdName=忠诚向上, createdTime=Mon Mar 14 12:07:00 CST 2016, time=2016-03-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=69279, encodeId=41e3692e98b, content=好好学习,继续研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=109, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45101626056, createdName=忠诚向上, createdTime=Mon Mar 14 12:07:00 CST 2016, time=2016-03-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=69280, encodeId=408d6928035, content=好好学习,继续研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45101626056, createdName=忠诚向上, createdTime=Mon Mar 14 12:07:00 CST 2016, time=2016-03-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1422694, encodeId=0a021422694bf, content=<a href='/topic/show?id=54fa80e701' target=_blank style='color:#2F92EE;'>#GLP-1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8077, encryptionId=54fa80e701, topicName=GLP-1)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f8f23732777, createdName=yibei, createdTime=Thu Dec 10 10:55:00 CST 2015, time=2015-12-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1621998, encodeId=d80b162199826, content=<a href='/topic/show?id=392480e970' target=_blank style='color:#2F92EE;'>#GLP-1RA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8079, encryptionId=392480e970, topicName=GLP-1RA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f14520287581, createdName=bioon10, createdTime=Thu Dec 10 10:55:00 CST 2015, time=2015-12-10, status=1, ipAttribution=)]
    2016-03-14 忠诚向上

    好好学习,继续研究

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1658658, encodeId=dca8165865870, content=<a href='/topic/show?id=4b4d80e878' target=_blank style='color:#2F92EE;'>#GLP-1R#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8078, encryptionId=4b4d80e878, topicName=GLP-1R)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=fea024898996, createdName=360611848, createdTime=Tue Mar 08 18:55:00 CST 2016, time=2016-03-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=69274, encodeId=0b93692e416, content=好好学习,继续研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=88, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45101626056, createdName=忠诚向上, createdTime=Mon Mar 14 12:07:00 CST 2016, time=2016-03-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=69275, encodeId=2356692e542, content=好好学习,继续研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=92, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45101626056, createdName=忠诚向上, createdTime=Mon Mar 14 12:07:00 CST 2016, time=2016-03-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=69276, encodeId=c56a692e68f, content=好好学习,继续研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=101, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45101626056, createdName=忠诚向上, createdTime=Mon Mar 14 12:07:00 CST 2016, time=2016-03-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=69277, encodeId=9377692e731, content=好好学习,继续研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=118, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45101626056, createdName=忠诚向上, createdTime=Mon Mar 14 12:07:00 CST 2016, time=2016-03-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=69278, encodeId=f2b9692e849, content=好好学习,继续研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45101626056, createdName=忠诚向上, createdTime=Mon Mar 14 12:07:00 CST 2016, time=2016-03-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=69279, encodeId=41e3692e98b, content=好好学习,继续研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=109, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45101626056, createdName=忠诚向上, createdTime=Mon Mar 14 12:07:00 CST 2016, time=2016-03-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=69280, encodeId=408d6928035, content=好好学习,继续研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45101626056, createdName=忠诚向上, createdTime=Mon Mar 14 12:07:00 CST 2016, time=2016-03-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1422694, encodeId=0a021422694bf, content=<a href='/topic/show?id=54fa80e701' target=_blank style='color:#2F92EE;'>#GLP-1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8077, encryptionId=54fa80e701, topicName=GLP-1)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f8f23732777, createdName=yibei, createdTime=Thu Dec 10 10:55:00 CST 2015, time=2015-12-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1621998, encodeId=d80b162199826, content=<a href='/topic/show?id=392480e970' target=_blank style='color:#2F92EE;'>#GLP-1RA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8079, encryptionId=392480e970, topicName=GLP-1RA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f14520287581, createdName=bioon10, createdTime=Thu Dec 10 10:55:00 CST 2015, time=2015-12-10, status=1, ipAttribution=)]
    2016-03-14 忠诚向上

    好好学习,继续研究

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=1658658, encodeId=dca8165865870, content=<a href='/topic/show?id=4b4d80e878' target=_blank style='color:#2F92EE;'>#GLP-1R#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8078, encryptionId=4b4d80e878, topicName=GLP-1R)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=fea024898996, createdName=360611848, createdTime=Tue Mar 08 18:55:00 CST 2016, time=2016-03-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=69274, encodeId=0b93692e416, content=好好学习,继续研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=88, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45101626056, createdName=忠诚向上, createdTime=Mon Mar 14 12:07:00 CST 2016, time=2016-03-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=69275, encodeId=2356692e542, content=好好学习,继续研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=92, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45101626056, createdName=忠诚向上, createdTime=Mon Mar 14 12:07:00 CST 2016, time=2016-03-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=69276, encodeId=c56a692e68f, content=好好学习,继续研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=101, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45101626056, createdName=忠诚向上, createdTime=Mon Mar 14 12:07:00 CST 2016, time=2016-03-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=69277, encodeId=9377692e731, content=好好学习,继续研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=118, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45101626056, createdName=忠诚向上, createdTime=Mon Mar 14 12:07:00 CST 2016, time=2016-03-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=69278, encodeId=f2b9692e849, content=好好学习,继续研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=98, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45101626056, createdName=忠诚向上, createdTime=Mon Mar 14 12:07:00 CST 2016, time=2016-03-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=69279, encodeId=41e3692e98b, content=好好学习,继续研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=109, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45101626056, createdName=忠诚向上, createdTime=Mon Mar 14 12:07:00 CST 2016, time=2016-03-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=69280, encodeId=408d6928035, content=好好学习,继续研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45101626056, createdName=忠诚向上, createdTime=Mon Mar 14 12:07:00 CST 2016, time=2016-03-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1422694, encodeId=0a021422694bf, content=<a href='/topic/show?id=54fa80e701' target=_blank style='color:#2F92EE;'>#GLP-1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8077, encryptionId=54fa80e701, topicName=GLP-1)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f8f23732777, createdName=yibei, createdTime=Thu Dec 10 10:55:00 CST 2015, time=2015-12-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1621998, encodeId=d80b162199826, content=<a href='/topic/show?id=392480e970' target=_blank style='color:#2F92EE;'>#GLP-1RA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8079, encryptionId=392480e970, topicName=GLP-1RA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f14520287581, createdName=bioon10, createdTime=Thu Dec 10 10:55:00 CST 2015, time=2015-12-10, status=1, ipAttribution=)]
    2016-03-14 忠诚向上

    好好学习,继续研究

    0

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    2016-03-14 忠诚向上

    好好学习,继续研究

    0

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    2015-12-10 yibei
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    2015-12-10 bioon10

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