Incretin-based drugs for type 2 diabetes: Focus on East Asian perspectives.
Incretin-based drugs for type 2 diabetes: Focus on East Asian perspectives.
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DOI：
10.1111/jdi.12490
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发表时间：
2016-04
影响因子：
3.2
通讯作者：
Yabe D
中科院分区：
文献类型：
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作者：
Seino Y;Kuwata H;Yabe D
东亚人的2型糖尿病的主要特征是β细胞功能障碍，与高加索人相比，肥胖和胰岛素抵抗较少。这种病理生理学差异可以决定疾病的适当治疗方法。肠降血糖素、葡萄糖依赖性促胰岛素多肽和胰高血糖素样肽-1在进食时分泌，并以葡萄糖依赖性方式增强胰岛素分泌。基于肠促胰岛素的药物、二肽基肽酶-4抑制剂（DPP-4 i）和胰高血糖素样肽-1受体激动剂可改善β细胞功能障碍，低血糖风险有限，目前已广泛用于2型糖尿病管理。最近对DPP-4 i和胰高血糖素样肽-1受体激动剂临床试验的Meta分析发现，这些药物在亚洲人中更有效，最可能是因为改善了β细胞功能障碍。此外，我们发现DPP-4 i降低糖化血红蛋白的作用增加与2型糖尿病患者摄入鱼类相关，这表明东亚人的饮食习惯也可能是DPP-4 i更大疗效的基础。尽管风险有限，但DPP-4 i/磺脲类药物联合治疗仍报告了重度低血糖病例。重要的是，在同时接受格列本脲或格列美脲治疗的患者中，低血糖发生率更高，因为格列本脲或格列美脲可激活由环磷酸腺苷2直接激活的交换蛋白（肠促胰岛素信号传导的关键介质），而格列齐特治疗的患者中低血糖发生率较低，格列齐特不能激活由环磷酸腺苷2直接激活的交换蛋白。DPP-4 i预防胰岛素相关低血糖的作用因促胰岛素多肽增强低血糖诱导的胰高血糖素分泌而受到关注，但仍有待在东亚人中进行研究。尽管安全性问题至关重要，必须仔细监测，但基于肠促胰岛素的药物可能成为东亚2型糖尿病患者的首选治疗。
Type 2 diabetes in East Asians is characterized primarily by β‐cell dysfunction, and with less adiposity and less insulin resistance compared with that in Caucasians. Such pathophysiological differences can determine the appropriate therapeutics for the disease. Incretins, glucose‐dependent insulinotropic polypeptide and glucagon‐like peptide‐1, are secreted in response to meal ingestion, and enhance insulin secretion glucose‐dependently. Incretin‐based drugs, dipeptidyl peptidase‐4 inhibitors (DPP‐4i) and glucagon‐like peptide‐1 receptor agonists, that ameliorate β‐cell dysfunction with limited hypoglycemia risk are now widely used in type 2 diabetes management. Recent meta‐analyses of clinical trials on DPP‐4i and glucagon‐like peptide‐1 receptor agonists found that the drugs were more effective in Asians, most likely because of amelioration of β‐cell dysfunction. In addition, we found increased glycated hemoglobin‐lowering effects of DPP‐4i to be associated with intake of fish in type 2 diabetes, which suggests that dietary customs of East Asians might also underlie the greater efficacy of DPP‐4i. Despite the limited risk, cases of severe hypoglycemia were reported for DPP‐4i/sulfonylureas combinations. Importantly, hypoglycemia was more frequent in patients also receiving glibenclamide or glimepiride, which activate exchange protein directly activated by cyclic adenosine monophosphate 2, a critical mediator of incretin signaling, and was less frequent in patients receiving gliclazide, which does not activate exchange protein directly activated by cyclic adenosine monophosphate 2. Prevention of insulin‐associated hypoglycemia by DPP‐4i has gained attention with regard to the enhancement of hypoglycemia‐induced glucagon secretion by insulinotropic polypeptide, but remains to be investigated in East Asians. Despite the safety issues, which are paramount and must be carefully monitored, the incretin‐based drugs could have potential as a first choice therapy in East Asian type 2 diabetes patients.