钠-葡萄糖共转运蛋白2抑制剂治疗2型糖尿病的临床研究进展

2 型糖尿病是一种以胰岛素分泌缺陷、胰岛素抵抗或者两者并存所致的高血糖为特征的慢性代谢性疾病。早期血糖控制不佳可以促进微血管并发症的进展,以及大血管风险的发生。虽然有众多的降糖药物在临床使用,但只有约50%的患者能实现血糖控制,传统药物仍存在某些不足,因此,需要开发具有新机制的治疗药物。钠-葡萄糖共转运蛋白2（SGLT2）是近年来发现的具有全新作用机制的一个糖尿病治疗靶点。SGLT2 抑制剂通过抑制肾脏近端小管对葡萄糖的重吸收来增加尿中葡萄糖的排泄而达到控制血糖的目的,其独立于葡萄糖依赖的胰岛素途径,能使低血糖发生风险降低。临床试验数据表明,SGLT2 抑制剂单药治疗和与传统降糖药物联合治疗均可以有效地控制血糖,并改善胰岛素抵抗,同时也有降血压和减少体质量作用。尽管后续的研究显示了SGLT2 抑制剂具有良好的耐受性,该类药物在临床上报道的意想不到的风险仍需要大量和长期的临床数据证实。     

二肽基肽酶-4抑制剂临床应用研究进展

二肽基肽酶-4（DPP-4）抑制剂是近年来出现的一种新的治疗2型糖尿病的药物,具有降糖作用显著,安全性良好,不增加体质量和低血糖风险,长期应用对胰岛β-细胞具有保护作用等优点。本文将从其作用机制,疗效,安全性方面概述这类药物。     

二肽基肽酶Ⅳ抑制剂治疗2型糖尿病肥胖患者的临床研究进展

目的:为2型糖尿病肥胖患者临床合理用药提供参考。方法:查阅二肽基肽酶Ⅳ抑制剂(DPP-4抑制剂)治疗2型糖尿病肥胖患者的临床试验及相关文献,分析药物对患者治疗指标及安全性的影响,如血糖、体质量、心血管并发症和不良反应。结果与结论:DPP-4抑制剂在2型糖尿病肥胖患者中具有良好的降糖作用,同时对血脂异常、高血压和冠状动脉粥样硬化性心脏病等心血管并发症也有较好的效果,但对患者体质量减轻效果不明显。此类药物安全性和耐受性良好,但西格列汀治疗后有可能引起胰腺不良反应和胰腺炎。     

治疗2型糖尿病药物二肽基肽酶IV(DPP-4)抑制剂的研究进展

2型糖尿病是最常见的慢性病之一。DPP-4抑制剂是治疗2型糖尿病的新药,目前已有大量研究报道了不同结构的DPP-4抑制剂。本文主要根据当前进入临床前和,洛床研究阶段的DPP4抑制剂候选药物的数据,对DPP4抑制剂的化学结构类型进行分类,综述它们的药理、药效和构效关系,并对DPP-4抑制剂的研发进展进行展望。     

二肽基肽酶-4(DPP-4)抑制剂西格列汀在2型糖尿病治疗中的作用

目的:介绍新型口服降糖药二肽基肽酶-4(DPP-4)抑制剂西格列汀及其最新研究进展。方法 :对西格列汀的药理作用、药代动力学、不良反应及药物相互作用等方面的临床研究进行论述。结果和结论 :西格列汀是一种安全、有效的新型口服降糖药,具有良好的临床应用前景。     

二肽基肽酶-4抑制剂在2型糖尿病治疗中的作用

二肽基肽酶-4（DPP-4）抑制剂可选择性抑制DPP-4的活性,阻止胰升糖素样肽-1（GLP-1）裂解失活,提高活性GLP-1的血浆水平,增强其生理作用.该药临床用于治疗2型糖尿病,其能够改善2型糖尿病患者的糖脂代谢、减少β细胞凋亡和促进β细胞增殖,具有降低糖化血红蛋白水平、减少低血糖和副反应发生等作用,在2型糖尿病治疗中有广泛的应用前景.     

DPP-4抑制剂治疗2型糖尿病的研究进展及临床应用

DPP-4抑制剂是治疗2型糖尿病的新型药物。较传统的降糖药物而言,DPP-4抑制剂对降低2型糖尿病患者的血糖有更好的疗效,可以降低低血糖的危险,安全性及耐受性良好。本文通过分析DPP-4抑制剂类药物,综述其化学性质、物理作用、临床研究和当前待解决的问题,对DPP-4抑制剂类药物的研究进展及临床应用疗效进行探究和展望。     

奥格列汀:一种新的长效二肽基肽酶-4抑制剂

糖尿病是一种以高血糖为特征的代谢性疾病,目前常用的口服降糖药均需要每天服药,给患者带来不便。奥格列汀是一个小分子二肽基肽酶-4（DPP-4）抑制剂,由默克公司研发,主要用于二型糖尿病的治疗,且只需1周服用1次即可,从而提高了患者的顺应性和坚持性,最终提高了治疗效果。介绍了奥格列汀的合成方法、药理学、药物代谢动力学、临床研究等信息,为更好地应用临床与研发类似新药提供依据。     

钠-葡萄糖协同转运蛋白2抑制剂类抗糖尿病新药的研发概况

目前,钠-葡萄糖协同转运蛋白2(SGLT2)抑制剂通过抑制葡萄糖在肾脏近曲小管的重吸收,从而成为治疗糖尿病的新途径。按其结构,SGLT2抑制剂主要分为C-芳基抑制剂、O-芳基抑制剂、S-糖苷抑制剂和N-糖苷抑制剂,而C-芳基抑制剂和O-芳基抑制剂处于研究热点,其中几个新药(dapagliflozin、canagliflozin、ASP1941、BI10773和LX4211)显示出良好的控制血糖水平和减轻体质量的效果,且不良反应较小。综述两类结构中的主要药物研究概况,并分析其研发前景。     

二肽基肽酶-4抑制剂研究进展

二肽基肽酶-4抑制剂为一类常用的2型糖尿病治疗药物,可通过抑制二肽基肽酶-4活性延长胰高血糖素样肽-1的作用时间和促进胰岛素分泌,从而降低血糖水平。根据化学结构类型的不同,将二肽基肽酶-4抑制剂分为拟肽类和非拟肽类抑制剂,并分别介绍其药理活性、构效关系及药动学特性等方面的研究进展。     

DPP-4 inhibitor plus SGLT-2 inhibitor as combination therapy for type 2 diabetes: from rationale to clinical aspects

Introduction: Type 2 diabetes (T2D) is a complex disease with multiple defects, which generally require a combination of several pharmacological approaches to control hyperglycemia. Combining a dipeptidyl peptidase-4 inhibitor (DPP-4i) and a sodium-glucose cotransporter type 2 inhibitor (SGT2i) appears to be an attractive approach.

Area covered: An extensive literature search was performed to analyze the pharmacokinetics, pharmacodynamics and clinical experience of different gliptin-gliflozin combinations.

Expert opinion: There is a strong rationale for combining a DPP-4i and a SGLT2i in patients with T2D because the two drugs exert different and complementary glucose-lowering effects. Dual therapy (initial combination or stepwise approach) is more potent than either monotherapy in patients treated with diet and exercise or already treated with metformin. Combining the two pharmacological options is safe and does not induce hypoglycemia. The additional glucose-lowering effect is more marked when a gliflozin is added to a gliptin than when a gliptin is added to a gliflozin. Two fixed-dose combinations (FDCs) are already available (saxagliptin-dapagliflozin and linagliptin-empagliflozin) and others are in current development. Bioequivalence of the two compounds given as FDC tablets was demonstrated when compared with coadministration of the individual tablets. FDCs could simplify the anti-hyperglycaemic therapy and improve drug compliance.     

基础胰岛素与二肽基肽酶－4抑制剂联合治疗2型糖尿病的临床观察

目的：观察基础胰岛素与二肽基肽酶－4抑制剂联合治疗2型糖尿病的临床疗效。方法：将80例2型糖尿病患者（空腹血糖＞11．1 mmol／L）以随机数字表法分为观察组与对照组各40例,观察组患者给予地特胰岛素与西格列汀联合治疗,对照组患者给予地特胰岛素与瑞格列奈联合治疗,观察2组患者的临床疗效。结果：观察组患者空腹及餐后2h血糖、糖化血红蛋白、血脂谱、体质量指数较治疗前明显下降（P＜0．05）,且各项指标改善情况均优于对照组（P＞0．05）;2组患者胰岛β细胞功能均较治疗前明显下降,观察组改善情况优于对照组（P＜0．05）;2组患者不良反应均较少,差异无统计学意义（P＞0．05）;2组患者血糖达标率及血糖达标中位时间的差异有统计学意义（P＜0．05）。结论：基础胰岛素与二肽基肽酶－4抑制剂联合治疗2型糖尿病,具有较好的临床疗效,且安全性高,值得推广。     

2型糖尿病治疗新药坎格列净的研究进展

坎格列净是一种钠-葡萄糖共转运蛋白2抑制药,抑制葡萄糖的肾重吸收,增加葡萄糖的尿排泄.美国FDA于2013年3月批准其上市,用于治疗2型糖尿病.坎格列净可有效降低2型糖尿病患者的血糖水平,还可降低患者体质量和收缩压,且低血糖风险较小.不良反应是增加泌尿生殖道感染.本文就其作用机制、药动学、临床疗效及安全性等作一综述.     

DPP-4的基因组学研究进展与DPP-4抑制剂的临床应用

二肽基肽酶IV(DPP-4)是一种分布广泛的膜相关性丝氨酸蛋白酶,能够影响糖代谢、脂质代谢、免疫调节、神经调节、信号转导、癌症发展等多种生理功能。随着全基因组关联研究(GWAS)的发展,DPP-4基因的基因多态性,主要是单核苷酸多态性已被证实影响血脂水平和mRNA表达,还影响心血管疾病的易感性,可能与DPP-4抑制剂在血脂紊乱和心血管疾病方面的疗效具有密切关系,这在2型糖尿病的治疗中具有重要意义。本文对国内外所有关于DPP-4基因多态性的研究进行综述,并在此基础上探讨其对DPP-4抑制剂在2型糖尿病治疗中的影响。     

An update on the safety and efficacy of oral antidiabetic drugs: DPP-4 inhibitors and SGLT-2 inhibitors

Introduction: Oral antidiabetic medications are important in many type 2 diabetes care plans

Areas covered: The article summarizes the cardiovascular and renal safety data for DPP-4 inhibitors and SGLT-2 inhibitors and specific safety data particular to each class.

Expert opinion: DPP-4 and SGLT-2 inhibitors provide unique anti-hyperglycemic mechanisms. The cardiovascular safety profiles of DPP-4 inhibitors are promising, but do not show the strong CV risk reduction of empagliflozin and canagliflozin. The heart failure signal associated with DPP-4 inhibitor use is unclear with differing agents, demonstrating increased risk or maybe even protective effects. The risk reduction in cardiovascular disease associated with SGLT-2 inhibitors has translated to recommendations to consider these therapies early in the treatment pathway. Both classes have potential safety concerns that necessitate appropriate patient selection and thorough education on potential side-effects. DPP-4 inhibitors are considered to have neutral or in some studies beneficial renoprotective effects. SGLT-2 inhibitor safety effects on the kidney are more complex. There are reports of acute kidney injury occurring soon after initiating SGLT-2 inhibitor therapy. However, there are large recent studies that have demonstrated the beneficial effect of SGLT-2 inhibitors in slowing the progression of established chronic kidney disease.     

治疗2型糖尿病的DPP-4抑制药及其知识产权分析

DPP-4抑制药是近年来研发及上市的新一类口服降糖药物及热点药物,其为2型糖尿病的临床治疗提供了新的选择。国内目前批准及临床应用的治疗2型糖尿病的DPP-4抑制药全部为进口产品。本文对国内外研发与批准上市的DPP-4抑制药知识产权现状进行了详细的研究分析,合理利用好即将专利到期或专利已经失效的DPP-4抑制药相关专利信息,可很好地指导国内针对疗效确切、市场前景好的DPP-4抑制药进行仿创性结合的后续开发,并可产生新的专利,以增强市场竞争力。     

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。     

The safety of DPP-4 inhibitor and SGLT2 inhibitor combination therapies

Introduction: Type 2 diabetes (T2D), a multifactorial and chronic disease, requires in an elevated percentage of patients the association of several antidiabetic drugs to achieve optimal glycemic control. Dipeptidyl peptidase-4 inhibitors (DPP-4i) and sodium–glucose cotransporter inhibitors (SGLT2i) are new classes of oral antidiabetic drugs developed over the last years.

Areas covered: This paper summarizes the safety of DPP-4i and SGLT2i combination therapies. Relevant studies were identified through searches in PubMed.

Expert opinion: DPP4i and SGLT2i are antidiabetic drugs that lower blood glucose without causing hypoglycaemia or weight increase. More importantly, cardiovascular trials have clearly demonstrated the cardiovascular safety of DPP4i and a reduction in cardiovascular events with SGLT2i (empagliflozin and canagliflozin). Therefore, the association of both therapeutic groups could be an attractive option to achieve optimal blood glucose control in T2D because of their complementary mechanism of action. Clinical trials evaluating the combination of SGLT2i and DPP4i show that the co-administration of these drugs in fixed-dose combinations in comparison to separate tablets does not carry additional safety concerns that each individual drug, but increases therapeutic effects. Therefore, this antidiabetic combination is a safe and effective therapy for patients with T2D.