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二肽基肽酶Ⅳ（DDP-4）抑制剂在糖尿病中的应用——Philip Home 教授访谈 1.People have always been focused on drug therapy for 2-DM patients. The United Kingdom Prospective Diabetes Study (UKPDS) has suggested that regardless of treatment, β-cell function of islet in diabetic patients would loss progressively. Traditional antidiabetic drugs can not protectβ-cell function and stimulate β-cell to regenerate. Some studies have suggested that glucagon like peptide-1 may stimulate insulin secretion then lower the blood glucose and also increaseβ-cell function and volume. Currently two types of incretin based therapies including GLP-1 analogue and Dipeptidyl peptidase 4（DDP-4）inhibitor have developed. Would you please talk about the current research status and future development perspectives of these drugs? 2型糖尿病治疗药物向来是人们关注的焦点，英国前瞻性糖尿病研究（UKPDS）结果显示无论采取何种治疗手段，糖尿病患者胰岛β细胞功能均进行性丧失。传统的降糖药物无保护胰岛β细胞功能和促其新生的作用，研究发现胰升糖素样肽-1不仅促进胰岛素分泌而起到降低血糖作用，而且还增加胰岛β细胞功能和体积，从而研制出了肠促胰岛素类似物和二肽基肽酶Ⅳ（DDPIV）抑制剂两类药物。请您跟我们谈谈这类药物目前的研发状态以及将来的发展前景吧。 2.In October 2006,the new drug Sitagliptin Phosphate(Merck company), Dipeptidyl peptidase 4（DDP-4）inhibitor, got the FDA approval, which drew lots of attentions to this new therapeutic class. Because sitagliptin phosphate is the first DDP-4 inhibitor approved for the treatment of type 2 diabetes, could you (talk about the latest study results about efficacy of this drug?) please comment on the differences of this drug from the current oral antidiabetics, and its possible position or status in the clinical management of T2DM in future? 2006年10月默克公司用于治疗2型糖尿病的新药二肽基肽酶Ⅳ（DDP-4）抑制剂sitagliptin phosphate获美国FDA的批准获准上市，引起了人们对这一类新型药物的普遍关注。由于sitagliptin phosphate是第一个上市的DPP－4抑制剂，请您谈谈(目前最新的关于该药物疗效方面的研究结果)该药与现有治疗有哪些不同之处，将来在2型糖尿病临床治疗中可能具有的地位。 3.DDP－4 inhibitors can stimulate insulin secretion, but do not result in hypoglycemia. Could you please talk about physiopathologic mechanism of DDP-4 inhibitors in this aspect? DPP IV抑制剂能刺激胰岛素的分泌，但并不引起低血糖，请您谈一下DPP－4抑制剂在这方面的病理生理基础吧？（不引起低血糖与B细胞保护无关） 4.The aged diabetes mellitus is always the difficulty in DM therapy, and it refers to combination with other medications, and so on. Could you please talk about the features and advantages of DPP-4 inhibitors in this aspect? Particularly, the evidences about combination therapy? 老年人糖尿病治疗一直是糖尿病治疗的一个难点，涉及联合用药等问题，请您谈谈二肽基肽酶Ⅳ（DDPIV）抑制剂在这方面有哪些特点和优势呢?特别是联合用药的循证证据。 5.People pay close attention to drug safety in current drug development. Weight gain is a common adverse effect for most oral antidiabetic drugs. This may decrease patients' compliance and increase the risk of cardiovascular diseases. Do DDP-4 inhibitors have any advantage in this aspect? Does current clinical practice support this advantage? 目前药物的开发更倾向于对安全性的更高要求。体重增加是大多数口服降糖药用药后常见的不良反应，这一点可能降低依从性，并且可能增加发生心血管病的风险。DPP－4抑制剂在这方面有优势吗？目前临床实践对此有无支持？ 6.Preclinical studies have indicated that increasing the level of incretin may improve and protect the function of β-cell. Then can we think that the drug containing DDPⅣ inhibitor may have the similar effect for other hormone, neuropeptide and cytokine? In 2007 European Association for the Study of Diabetes, it is announced that DDP Ⅳ inhibitor can impact anabolism of fatty tissue through adjusting the antilipotropism of NPY in the fatty tissue. What do you think about this problem? 临床前研究表明增加肠促胰岛素水平能改善和保护β细胞功能。那么是否可以认为含DPP IV抑制剂的药物对于其他激素，神经肽和细胞因子也可能有类似的作用？在2007EASD会议上就公布了一项关于DPP IV抑制剂通过调节脂肪组织中的NPY抗亲脂作用而影响脂肪组织代谢的研究结果，您对这个问题怎么看呢？ |
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