Barnett A
Department of Medicine, University of Birmingham and Heart of England National Health Service Foundation Trust (Teaching), Birmingham, UK.
Int J Clin Pract. 2006 Nov;60(11):1454-70. doi: 10.1111/j.1742-1241.2006.01178.x.
The dipeptidyl peptidase 4 (DPP-4) inhibitors enhance the body's own ability to control blood glucose by increasing the active levels of incretin hormones in the body. Their mechanism of action is distinct from any existing class of oral glucose-lowering agents. They control elevated blood glucose by triggering pancreatic insulin secretion, suppressing pancreatic glucagon secretion, and signalling the liver to reduce glucose production. The leading DPP-4 inhibitors have shown clinically significant HbA1c reductions up to 1 year of treatment and offer many potential advantages over existing diabetes therapies including a low risk of hypoglycaemia, no effect on body weight, and the potential, based on animal and in vitro studies, for the regeneration and differentiation of pancreatic beta-cells. They are efficacious as monotherapy and also in combination with commonly prescribed antidiabetic agents and are suitable for once-daily oral dosing. Consequently, many DPP-4 inhibitors such as vildagliptin (Galvus; LAF-237), sitagliptin (Januvia; MK-0431), and saxagliptin (BMS-477118) have advanced into late-stage human clinical trials. Search strategy and selection criteria This review was built on a systematic MEDLINE search for publications on the subject with the key words: DPP-4 inhibitor; vildagliptin (LAF-237); sitagliptin (MK-0431); saxagliptin (BMS-477118); and type 2 diabetes; up to August 2006. Meeting abstracts were also searched, as much of the data currently only exists in abstract form. Take home message for clinician The DPP-4 inhibitors appear to have great potential for the treatment of type 2 diabetes, but time will tell if this will be realized. While they do not lower glucose to a greater extent than existing therapies, they offer many potential advantages, including the ability to achieve sustainable reductions in HbA1c with a well-tolerated agent that has a low risk of hypoglycaemia and no weight gain, and which can be administered as a once-daily oral dose.
二肽基肽酶4（DPP - 4）抑制剂通过提高体内肠促胰岛素激素的活性水平，增强机体自身控制血糖的能力。其作用机制与现有的任何一类口服降糖药都不同。它们通过触发胰腺胰岛素分泌、抑制胰腺胰高血糖素分泌以及向肝脏发出信号以减少葡萄糖生成来控制血糖升高。领先的DPP - 4抑制剂在长达1年的治疗中已显示出具有临床意义的糖化血红蛋白（HbA1c）降低，并且与现有的糖尿病治疗方法相比具有许多潜在优势，包括低血糖风险低、对体重无影响，以及基于动物和体外研究显示的胰腺β细胞再生和分化的潜力。它们作为单一疗法有效，也可与常用的抗糖尿病药物联合使用，并且适合每日一次口服给药。因此，许多DPP - 4抑制剂，如维格列汀（佳维乐；LAF - 237）、西他列汀（捷诺维；MK - 0431）和沙格列汀（安立泽；BMS - 477118）已进入后期人体临床试验阶段。检索策略和选择标准本综述基于对MEDLINE系统检索有关该主题的出版物，关键词为：DPP - 4抑制剂；维格列汀（LAF - 237）；西他列汀（MK - 0431）；沙格列汀（BMS - 477118）；以及2型糖尿病；截至2006年8月。还检索了会议摘要，因为目前许多数据仅以摘要形式存在。给临床医生的关键信息DPP - 4抑制剂在2型糖尿病治疗中似乎具有巨大潜力，但这是否能够实现还需时间检验。虽然它们降低血糖的程度并不比现有疗法更大，但它们具有许多潜在优势，包括能够通过一种耐受性良好、低血糖风险低且无体重增加的药物实现糖化血红蛋白的持续降低，并且可以每日一次口服给药。
