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二肽基肽酶4抑制剂治疗2型糖尿病

Authors
Kathleen Dungan, MD
Anthony DeSantis, MD
Section Editor
David M Nathan, MD
Deputy Editor
Jean E Mulder, MD
Translators
于楠, 主治医师

引言

目前2型糖尿病药物治疗的基础是增加可用的胰岛素(直接给予胰岛素或给予促进胰岛素分泌的药物)、改善胰岛素敏感性、延缓胃肠道对碳水化合物的运输和吸收或增加尿糖排出。针对胰高血糖素样肽-1(glucagon-like peptide-1, GLP-1)的治疗[如二肽基肽酶4(dipeptidyl peptidase 4, DPP-4)抑制剂、GLP-1受体激动剂]可通过多种机制影响血糖控制，包括增强葡萄糖依赖的胰岛素分泌、延缓胃排空，以及减少餐后胰高血糖素分泌和食物摄取(表 1)。

本专题将总结DPP-4抑制剂治疗2型糖尿病的作用机制及疗效。GLP-1受体激动剂将单独讨论。关于2型糖尿病血糖成人患者的初始血糖治疗及持续性高血糖处理的一般讨论也参见其他专题。 (参见“胰高血糖素样肽-1受体激动剂在2型糖尿病治疗中的应用”和“成人2型糖尿病的初始血糖管理”和“2型糖尿病患者持续高血糖的治疗”)

作用机制

GLP-1由小肠L细胞内的胰高血糖素原基因产生，在受到营养素刺激后分泌(图 1)[1]。GLP-1发挥主要作用的机制是刺激胰岛的葡萄糖依赖性胰岛素释放[2]。它也显示出可了缓胃排空[3]、抑制不适当的餐后胰高血糖素释放[1,4]及减少食物摄取的功效(表 1)。以GLP-1为基础的治疗，包括DPP-4抑制剂，通常不会引起低血糖，除非联用可引起低血糖的其他治疗。GLP-1是一种肠促胰岛素，是自然产生的胃肠激素家族中的一员，其在进餐后释放，但在静脉给予碳水化合物时不会产生，可刺激胰岛素合成和分泌。 (参见“胰高血糖素样肽-1受体激动剂在2型糖尿病治疗中的应用”，关于‘胰高血糖素样肽-1’一节)

DPP-4抑制剂是一类口服的糖尿病药物，可抑制DPP-4[5]。DPP-4是一种普遍存在的酶，在大多数类型细胞的表面都有表达，其可灭活多种其他生物活性肽，包括葡萄糖依赖性促胰岛素多肽(glucose-dependent insulinotropic polypeptide, GIP)和GLP-1；因此，对其进行抑制或可通过多种作用影响血糖调节。然而与GLP-1激动剂相比，DDP-4抑制剂对GLP-1的水平只有轻微影响。 (参见“胰高血糖素样肽-1受体激动剂在2型糖尿病治疗中的应用”)

候选者

在大多数2型糖尿病患者中都不考虑将DPP-4抑制剂作为初始治疗。大多数2型糖尿病患者的初始治疗应从饮食、减重、运动及使用二甲双胍(如无禁忌证)入手。患者不耐受二甲双胍、磺酰脲类或噻唑烷二酮类药物或存在禁忌证时(例如合并慢性肾脏病或低血糖风险极高)，可考虑采用DPP-4抑制剂单药治疗。对于应用二甲双胍、噻唑烷二酮类或磺酰脲类药物不能充分控制血糖的患者，可考虑将DPP-4抑制剂作为附加药物。然而，DPP-4抑制剂微弱的降糖效果、高昂的费用和有限的临床使用经验降低了我们对这类药物的热情。初始及后续疗法将单独详细总结。 (参见“成人2型糖尿病的初始血糖管理”，关于‘我们的方法’一节和“2型糖尿病患者持续高血糖的治疗”，关于‘治疗方案的选择’一节)

                

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Literature review current through: 2017-06 . | This topic last updated: 2017-06-12.
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