DPP-4抑制剂在2型糖尿病治疗中的作用

2型糖尿病已成为全球范围内发病率增长最快的疾病之一,其发病和进展的重要原因是：胰岛的β细胞胰岛素分泌缺陷和α细胞胰升糖素不适当的分泌造成的胰岛素与胰升糖素比例失调,目前药物治疗不能从根本上阻止β细胞和α细胞的功能恶化.肠促胰素能同时改善胰岛α及β细胞功能,成为治疗糖尿病的新靶点.由于其血浆半衰期仅2 min,很快被二肽基肽酶（DPP-4）降解,口服给药的DPP-4抑制剂成为2型糖尿病治疗的新选择.其作用机制抑制二肽基肽酶的活性,保护内源性肠促胰素活性,发挥葡萄糖依赖性降糖作用.其代表药物有西格列汀、维格列汀、沙格列汀等.其在2型糖尿病中的作用,能够显著降低HbA1c,空腹和餐后血糖,与磺脲类相比DPP-4抑制剂非劣效于磺脲类,由于是葡萄糖依赖性降糖,不会出现低血糖.能改善胰岛素抵抗,同时改善α及β细胞功能障碍,DPP-4抑制剂总体上不增加体重或轻度减轻体重,降低心血管事件的风险,有良好的安全性和耐受性,是2型糖尿病早期治疗的理想药物.     

胰升糖素样肽-1对胰岛β细胞胰岛素基因表达的调节作用

目的 研究不同浓度胰升糖素样肽-1（GLP-1）对大鼠胰岛β细胞胰岛素基因表达的影响,探讨GLP-1在2型糖尿病治疗中的作用。方法 不同刺激浓度的GLP-1（0nmol／L、1nmol／L、10nmol／L、10^2nmol／L、10^3nmol／L）与葡萄糖浓度分别为2．2mmol／L、5．5mmol／L、11.1mmol／L的RPMI1640营养液共培养24h后,提取细胞总RNA,运用半定量RT-PCR技术检测胰岛素基因表达的变化。结果 葡萄糖浓度为2．2mmol／L和5．5mmol／L时,随GLP-1浓度升高,胰岛素基因表达量呈钟型方式升高;葡萄糖浓度为11．1mmol／L时,随GLP-1浓度升高,胰岛素基因表达量呈浓度依赖性升高。结论 GLP-1以葡萄糖依赖和浓度依赖方式促进胰岛素基因的表达。     

GLP-1受体激动剂和DPP-4抑制剂对心血管系统的保护作用

胰高糖素样肽1(GLP-1)受体激动剂和二肽基肽酶-4(DPP-4)抑制剂是近年上市的治疗2型糖尿病的新型药物。GLP-1主要通过抑制心肌细胞凋亡、改善内皮细胞功能、减轻体重、降低血糖、降低血压、改善心肌收缩力、舒张血管等直接或间接发挥其心脏保护作用,GLP-1受体激动剂和DPP-4抑制剂对体重、血压和血脂等心血管危险因素有改善作用。GLP-1受体激动剂和DPP-4抑制剂作用于新靶点,具有其独特的优点,将会是一类抗糖尿病新药。     

DPP-4抑制剂对2型糖尿病依从性的影响

目前,2型糖尿病的发病率在世界范围内增长迅速,全世界约有2.46亿人患有2型糖尿病,我国2型糖尿病的总人数位居世界第一.然而对于血糖的良好持久控制并不乐观,尚存在诸多的困难.目前,治疗糖尿病的药物主要有胰岛素分泌促进剂(磺酰脲类、瑞格列奈)、胰岛素、胰岛素增敏剂(双胍类、噻唑烷二酮类)和α-葡萄糖苷酶抑制剂,但它们常具有不同程度的不良反应,如低血糖、体重增加、心血管不良反应等.     

胰升血糖素样肽-1受体的表达与细胞凋亡的相关性研究

胰升血糖素样肽-1(GLP-1)作为一种新型的降糖药物已逐渐应用于临床,有些学者认为GLP-1是继二甲双胍后的治疗2型糖尿病的又一重要的基础药物[1],发现它与胰岛β细胞的增殖与凋亡、血糖依赖性的胰岛素分泌、延缓胃排空和抑制食欲等有关。GLP-1的功能是由胰升血糖素     

DPP-4抑制剂研究进展

DPP-4抑制剂是一类用于治疗2型糖尿病的口服降糖新药,可改善血糖控制,并且不会诱发低血糖和增加体重。与原有药物相比,DPP-4抑制剂在用药安全性方面具有显著的优势。本综述介绍已上市的DPP-4抑制剂及其作用机理和临床研究。     

新型降糖药DPP-4抑制剂研究进展

二肽基肽酶-4 (dipeptidyl peptidase-4, DPP-4)是研发新型降糖药物的热门靶点。目前,已经发现许多DPP-4抑制剂,其中一些化合物已经进入临床应用。本文介绍了DPP-4抑制剂在降糖药中的地位及作用机制,综述了近年来不同结构类型DPP-4抑制剂的研究进展。     

DPP-4抑制剂治疗糖尿病国内研究现状

二肽基肽酶-4（DPP-4）抑制剂是一类新型口服降糖药物,其通过抑制DPP-4酶活性,提高体内内源性胰升糖素样肽1（GLP-1）水平,增强肠促胰素作用进而发挥降糖作用。DPP-4抑制剂除了能有效的控制血糖水平,还能保护胰岛功能,延缓疾病进程,在临床上已被广泛用于治疗糖尿病。本文通过查阅国内相关文献及资料,对相关科研成果进行总结归纳,就DPP-4抑制剂治疗糖尿病在国内的研究状况做一综述。     

DPP-4抑制剂不能替代磺脲类药物

胰岛素促泌剂是治疗2型糖尿病的重要手段。近年来,为了得到疗效更好,更安全的胰岛素促泌剂,人们做了大量的研究。二肽基肽酶-4（DPP-4）抑制剂就是一种基于肠促胰素的新型降糖药,它不仅具有胰岛素促泌效应,还有减少低血糖、不增加体重、改善糖脂代谢、减少B细胞凋亡等优点,有人提出其可能取代磺脲类药物。下面就从机制、疗效、经济学、并发症等等方面将两类药物进行比较,以指导I临床应用。     

DPP-4抑制剂治疗糖尿病的临床疗效

目的探讨DPP-4抑制剂治疗糖尿病的临床疗效。方法选取2013年3月—2015年3月晋中市第一人民医院收治的84例糖尿病患者,分为对照组和观察组,每组42例。对照组患者接受双胍类(二甲双胍)药物治疗,观察组患者在对照组基础上接受DPP-4抑制剂(西格列汀)治疗。比较两组患者的临床疗效及不良反应发生情况。结果观察组患者空腹血糖(FPG)、餐后2h血糖(2h PG)及糖化血红蛋白(Hb A1c)低于对照组,总有效率高于对照组,不良反应发生率低于对照组,差异有统计学意义(P<0.05)。结论 DPP-4抑制剂治疗糖尿病的临床疗效显著,不良反应少,安全性高。     

DPP-4抑制剂调节血糖外的作用

DPP-4抑制剂疗效的产生依赖于通过抑制二肽基肽酶Ⅳ使机体内源性的GLP-1水平升高.GLP-1受体分布广泛,除分布在胰岛外,还存在于胃、十二指肠、胰腺外分泌、脑干、丘脑、下丘脑、海马、心、肺、肾、肌细胞、脂肪细胞及肝脏,有证据表明GLP-1受体在内脏传入神经也有表达[1].目前学者们对GLP-1类似物和DPP-4抑制剂在治疗2型糖尿病方面进行了大量研究,本文对DPP-4抑制剂降糖以外的作用进一步进行探讨.     

DPP-4抑制剂的降糖作用机制

上个世纪三十年代,法国人LaBarre首次提出了＂肠促胰素＂这一概念。近年来的研究加深了人们对肠促胰素的认识,并且催生了一种新型的口服降糖药物——二肽基肽酶-4（DPP-4）抑制剂,它可以提高血液中内源性GLP-1和GIP的浓度,并最终改善血糖控制。目前已有数种DPP-4抑制剂在部分国家上市销售。这些药物的化学结构和药效／代动力学或许各有差异,但它们都能有效地降低血糖（HbAl。降低0．5％～1％）并具有良好的耐受性。本文将着重从A细胞和B细胞的双向调节方面阐述此类药物的作用机制。     

DPP-4抑制剂的用药方案

2型糖尿病的发病机制包括胰岛素抵抗和进行性B细胞分泌不足两个环节,通过肠促胰岛素(incretin)的作用而改善胰岛B和A细胞分泌功能及胰岛素敏感性,为2型糖尿病的治疗开辟了新的途径.     

市售DPP-4抑制剂类抗糖尿病药物的比较研究

DPP-4抑制剂是近年来上市的一类高效、高选择性抗2型糖尿病药物,通过检索文献,综述已上市的五种DPP-4抑制剂在结构、药代药动、选择性、药物相互作用、副作用等方面的差异.     

DPP-4抑制剂的心血管保护作用

二肽基肽酶-4（DPP-4）抑制剂作为一类新上市用于治疗2型糖尿病的药物,最新的荟萃分析结果显示[1],DPP-4抑制剂可以有效地降低糖化血红蛋白（HbA1c）0.6%～1.1%,与安慰剂相比不易出现低血糖,且不易引起严重不良反应。     

DPP-4 inhibitors in diabetic complications: role of DPP-4 beyond glucose control

Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) are an emerging class of antidiabetic drugs that constitutes approximately fifty percent of the market share of the oral hypoglycemic drugs. Its mechanism of action for lowering blood glucose is essentially via inhibition of the rapid degradation of incretin hormones, such as glucagon-like peptide (GLP)-1 and gastric inhibitory polypeptide (GIP), thus the plasma concentration of GLP-1 increases, which promotes insulin secretion from the pancreatic β cells and suppresses glucagon secretion from the α cells. In addition to the direct actions on the pancreas, GLP-1 exhibits diverse actions on different tissues through its action on GLP-1 receptor, which is expressed ubiquitously. Moreover, DPP-4 has multiple substrates besides GLP-1 and GIP, including cytokines, chemokines, neuropeptides, and growth factors, which are involved in many pathophysiological conditions. Recently, it was suggested that DPP-4 is a new adipokine secreted from the adipose tissue, which plays an important role in the regulation of the endocrine function in obesity-associated type 2 diabetes. Consequently, DPP-4 inhibitors have been reported to exhibit cytoprotective functions against various diabetic complications affecting the liver, heart, kidneys, retina, and neurons. This review outlines the current understanding of the effect of DPP-4 inhibitors on the complications associated with type 2 diabetes, such as liver steatosis and inflammation, dysfunction of the adipose tissue and pancreas, cardiovascular diseases, nephropathy, and neuropathy in preclinical and clinical studies.     

DPP-4 inhibitors: focus on safety

Introduction: Dipeptidyl peptidase inhibitors (DPP-4-i) are highly selective inhibitors of the enzyme DPP-4. They act by increasing levels of incretin hormones, which have potent effects on insulin and glucagon release, gastric emptying, and satiety. Our goal is to review the safety issues related to DPP-4-i.

Areas covered: This review is based upon a PubMed search of the literature using keywords alogliptin, linagliptin, saxagliptin, sitagliptin and vildagliptin, DPP-4-i, glucagon-like polypeptide-1 agonists, as well as extensive personal clinical trial experience with each of these agents. The current DPP-4-i have very different chemical structures. Saxagliptin has significant cytochrome P450 metabolism and carries a risk of drug interactions. Linagliptin has primarily entero-hepatic excretion, a benefit in renally impaired patients. A concern arose related to congestive heart failure in the SAVOR TIMI trial of saxagliptin. Several major cardiac studies are underway, with two concluded. Despite lingering uncertainty related to pancreatitis and pancreatic cancer, large randomized trials have not shown an increased risk with DPP-4-i treatment. Cutaneous adverse effects occur with a low frequency with some of these agents.

Expert opinion: DPP-4-i are an additional choice in the group of anti-hyperglycemics. Their principal advantage is a low incidence of hypoglycemia, making these agents desirable in patients such as the elderly and those with cardiac disease. Several large trials have hinted at less cardiac risk with DPP-4-i than with sulfonylureas. The CAROLINA Trial comparing linagliptin and glimepiride may provide a conclusive answer to this question.     

Adverse drug reaction update

Increasing numbers of articles on adverse drug reactions are published in a wide range of medical journals. To help keep you up-to-date with the latest advances worldwide on all aspects of adverse drug reactions, this section of the journal brings you information selected from the drug safety alerting service Reactions Weekly. The following reports are selected from the latest issues, summarizing the most important clinical studies, adverse reaction news, and expert opinion pieces published across a broad range of literature sources.