造福老年2型糖尿病人群,DPP-4抑制剂西格列汀让更多患者受益

2017-01-03 上海长征医院内分泌科第二军医大学甲亢眼病诊治中心 石勇铨 中国医学论坛报

我国糖尿病总患病率升高的同时,老年人群(≥60岁)患病率也明显增加。2010年流行病学调查结果显示,我国成人糖尿病患病率为11.6%,其中22.86%为≥60岁的老年患者。显然,老年糖尿病患者的管理需要更多的关注。一老年糖尿病“状况”多——合并用药,安全第一老年糖尿病患者并发症多、突发状况多,这与老年人机体重要脏器功能下降密切相关。老年糖尿病患者大多无典型的“三多一少”症状,常至出现各种并发症或伴

我国糖尿病总患病率升高的同时,老年人群(≥60岁)患病率也明显增加。2010年流行病学调查结果显示,我国成人糖尿病患病率为11.6%,其中22.86%为≥60岁的老年患者。显然,老年糖尿病患者的管理需要更多的关注。

老年糖尿病“状况”多——合并用药,安全第一

老年糖尿病患者并发症多、突发状况多,这与老年人机体重要脏器功能下降密切相关。老年糖尿病患者大多无典型的“三多一少”症状,常至出现各种并发症或伴随症状才诊断为糖尿病,且老年患者记忆力下降,治疗依从性差。因此,老年糖尿病患者往往具有较高的并发症发病率,同时,30%~40%的老年患者同时合并糖代谢紊乱、高血压、向心性肥胖、高甘油三酯血症(图1)。


图1 老年患者糖尿病主要并发症及发病率

老年糖尿病的“状况多”,致使合并用药增加,包括降糖药物的联合使用、治疗合并症的药物和其他并发症的治疗药物(图2),所以药物间相互作用的安全性格外重要。DPP-4抑制剂(如西格列汀)与其他降糖药物(二甲双胍、格列本脲、吡格列酮)及他汀类药物、抗高血压药、酮康唑、地尔硫卓、利福平、环孢菌素、华法林、地高辛等药物间无相互作用,并且这些药物不显著改变DPP-4抑制剂的药代动力学特征。老年人降糖治疗中选择西格列汀等药物安全性优势明显(图3)。


图2 老年患者合并用药情况统计


图3 同时服用的其它药物对DPP-4抑制剂的药物代谢动力学参数的影响

老年糖尿病患者肾功能减退多

时光留给人体的烙印越来越重,重要代谢器官——肾脏也不例外,多种危险因素可以加剧年龄相关的肾功能下降,那么逐渐下降的肾功能如何代谢DPP-4抑制剂呢(图4)?


图4 随年龄增长,肾小球滤过率(GFR)逐渐下降

研究证实,DPP-4抑制剂可用于肾功能减退患者。在中重度肾功能不全患者中,DPP-4抑制剂降糖作用不受影响,不影响肾功能。KDIGO在慢性肾脏病(CKD)的评估和管理指南中指出,当肾小球滤过率(GFR)>30ml/min(即CKD分期为1、2、3期)时,DPP-4抑制剂如西格列汀降低剂量使用(图5)。


图5 慢性肾功能不全患者降糖药物的选择

老年糖尿病患者的低血糖风险高

老年患者发生低血糖的频率更高,后果更严重,可增加心血管疾病风险、引起自主神经功能受损、增加老年2型糖尿病患者痴呆风险、加剧视网膜缺血缺氧损伤,很可能成为治疗依从性的显著障碍。所以,老年糖尿病人的血糖管理需要特别关注低血糖风险。


不可否认,临床所有降糖药物均存在低血糖风险。如何将风险降至最低,获得更高的成本-效益比是最重要的。DPP-4抑制剂基于肠促胰素(包括GLP-1和GIP,由肠道全天释放,进食时水平升高。DPP-4酶可快速灭活这些激素)的葡萄糖依赖性作用机制(图6),可以更好改善血糖控制,保持机体糖代谢稳态。


图6 DPP-4抑制剂作用机制

肠促胰素是参与葡萄糖稳态生理调节的内源性系统的一部分。血糖升高时,GLP-1和GIP会增加胰岛素合成并通过细胞内信号促使β细胞分泌胰岛素。同时GLP-1还能抑制α细胞分泌胰高糖素分泌,从而降低肝糖输出。通过增加并延长活性肠促胰素水平,DPP-4抑制剂以葡萄糖依赖性的方式,增加胰岛素释放,并降低胰高糖素水平。当血糖达到正常值时,其效应减弱,从而降低患者低血糖风险。

总 结

随着我国老龄化的加剧,老年糖尿病患者会越来越成为需要特别关注的人群。DPP-4抑制剂对于老年糖尿病患者有更多获益,其耐受性及安全性较好,低血糖风险较低且不增加体重。目前,DPP-4抑制剂已在全球范围应用于糖尿病患者的治疗中(单药治疗、起始联合用药、两药加用联合治疗等方案)。2013年,我国颁布的《中国老年医学会老年糖尿病诊疗措施专家共识》已经将DPP-4抑制剂西格列汀等列为老年2型糖尿病降血糖药物的一线选择方案。希望在不远的将来,DPP4抑制剂进入国家医保目录,造福更多的老年2型糖尿病患者。

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    2017-11-04 jklm09
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    2017-01-05 李东泽

    很好,不错,以后会多学习

    0

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    2017-01-05 gaoxiaoe
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