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CDS 2013:杨文英认为DPP-4抑制剂是“智能化”降糖药

2013-11-26 MedSci MedSci原创

  肠促胰素机制研制的DPP-4抑制剂之所以目前被大家看好,很重要的原因是由于这类药物的作用机制完全不同于目前市面上其他的降糖药物。它在人体内的作用机制是多方面的:在胰岛方面,它可以在刺激β细胞分泌胰岛素的同时抑制胰高糖素的分泌,而且这种作用机制是具有葡萄糖浓度依赖性的,因而可以最大限度地防止低血糖的发生;另外,它还可以抑制食欲中枢,可以在很好控制血糖的同时不增加体重。在11月22日的2013

  肠促胰素机制研制的DPP-4抑制剂之所以目前被大家看好,很重要的原因是由于这类药物的作用机制完全不同于目前市面上其他的降糖药物。它在人体内的作用机制是多方面的:在胰岛方面,它可以在刺激β细胞分泌胰岛素的同时抑制胰高糖素的分泌,而且这种作用机制是具有葡萄糖浓度依赖性的,因而可以最大限度地防止低血糖的发生;另外,它还可以抑制食欲中枢,可以在很好控制血糖的同时不增加体重。在11月22日的2013中华医学会糖尿病学分会第十七次全国学术会议上,中华医学会糖尿病学会荣誉主任委员、亚洲糖尿病学会副主席、中日友好医院内分泌代谢病中心主任杨文英分享了目前医学界对DPP-4抑制剂的共识。
  DPP-4抑制剂的作用机制:通过抑制二肽基肽酶-4(DPP-4)的活性,有效减少GLP-1的失活,在生理范围内增加有活性的GLP-1水平。目前已知的GLP-1可以通过刺激胰岛素、抑制升糖素、抑制胃排空和让胰岛细胞重生的方式来降低血糖,主要是以葡萄糖浓度依赖的方式促进胰岛素释放,并降低胰高糖素水平,发挥降低HbA1c、空腹血糖及餐后血糖的作用,因此杨文英介绍说这是一种“智能”的降糖方法。DPP-4抑制剂则正是使DPP-4失活从而不分解GLP-1。 
   DPP-4抑制剂的总体疗效:目前在中国已上市的DPP-4抑制剂药物有西格列汀、沙格列汀、维格列汀、利格列汀、阿格列汀等。根据临床,目前DPP-4抑制剂的总体疗效有如下汇报:(1)降低HbA1c幅度约为0.4~1.0%;(2)以二甲双胍为基础的联合治疗(加用DPP-4抑制剂和磺脲类、噻唑烷二酮类等),DPP-4抑制剂与对照药的疗效相当;(3)以中国2型糖尿病人群为研究对象,发现维格列汀与阿卡波糖的降低HbA1c的作用相似;(4)DPP-4抑制剂降低HbA1c的程度与基线HbA1c水平有一定的关系。
  DPP-4抑制剂的适应症以及不良反应:
  (1)适应症:适用于成人2型糖尿病患者的血糖控制;不能用于1型糖尿病或糖尿病酮症酸中毒患者;不推荐用于妊娠期、哺乳期妇女和儿童。
  (2)不良反应:常见不良反应有咽炎、头痛、上呼吸道感染等,但是其低血糖的发生率比磺脲类低;少见不良反应包括:超敏反应、血管神经水肿、肝酶升高、腹泻咳嗽等,另有研究发现沙格列汀可明显增加糖尿病患者的心衰住院风险。
  DPP-4抑制剂在肾功能不全患者中的应用:
  西格列汀:中、重度肾功能不全及需要透析的终末期肾病,需根据肌酐清除率调整剂量。
  维格列汀:中度或者重度肾功能不全或受血液透析治疗不推荐使用。
  沙格列汀:轻度肾功能不全需调整剂量;中重度肾功能不全剂量调整为2.5mg,每日一次;重度肾功能不全不推荐使用。
  利格列汀药物代谢不经肾,适应于所有情况的肾病患者。
  DPP-4抑制剂在肝功能不全患者中的应用:
  西格列汀:轻度或者中度肝功能不全不需要调整剂量;目前尚无严重肝功能不全患者使用的临床经验,因此不推荐。
  维格列汀:不推荐用于开始给药前肝酶大于正常上限3倍的患者;罕见有肝功能障碍(包括肝炎)的报告,因此用药过程中需进行定期检测;对于用药中发生肝酶异常者,在肝功能检测恢复正常后,不建议重新使用。
  沙格列汀:中度肝功能不全需谨慎;重度肝功能不全不推荐。
  利格列汀:不同程度的肝功能不全不需要调整剂量。
  阿格列汀:肝功能异常需谨慎使用,出现具有临床意义的肝酶升高或者肝功能检查异常结果持续或恶化需停用。
  DPP-4抑制剂引发超敏反应的报道:
  超敏反应:沙格列汀和阿格列汀上市后曾被报告出现严重超敏反应(包括速发过敏反应和血管性水肿),因此如果疑有严重超敏反应须立即停止使用。
  高敏反应:利格列汀有高敏反应(例如荨麻疹、血管性水肿、局部皮肤剥脱或支气管高敏反应)的临床研究报告,临床中使用时须注意观察相关方面的体征。
  DPP-4抑制剂在心衰患者的使用:
  维格列汀和沙格列汀:(1)NYHAI-II级的充血性心衰需慎用;(2)III-IV级充血性心衰不推荐使用。
  DPP-4抑制剂与半乳糖不耐受遗传疾病:
  沙格列汀及维格列汀含有乳糖,因此,半乳糖不耐受遗传疾病、Lapp乳糖酶缺乏症或葡萄糖-半乳糖吸收不良患者不得服用。
  联合用药的低血糖风险:
  西格列汀与磺脲类药物合用低血糖风险增加,需适当减少磺脲类药物的剂量。
  利格列汀与胰岛素、磺脲类合用时低血糖风险增加,需适当减少胰岛素和磺脲类药物的剂量。
  药物相互作用: 
   沙格列汀的代谢主要由CYP3A4/5介导,其主要代谢产物也是DPP-4抑制剂,其抑制活性作用是沙格列汀的二分之一,与强效CYP3A/5抑制剂(如酮康唑、阿扎那韦、克拉霉素、茚地那韦、伊曲康唑、奈法唑酮、奈非那韦、利托那韦、沙奎那韦和泰利霉素)合用时,应将沙格列汀的剂量限制为
2.5mg/天

  禁忌症:
  对药物或药物中任何一成分过敏者禁用。

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    2013-11-28 yangpeizhi
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    2013-11-28 gaoxiaoe

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