胰高血糖素样肽-1类似物药物的研究进展

目的 介绍胰高血糖素样肽-1(GLP-1)及其类似物药物在2型糖尿病治疗中的应用。方法 通过归纳总结近年来国内外相关文献,介绍了GLP-1的序列结构及其生理功能,并对其类似物药物(如Exendin-4,Liraglutide等)的临床应用或研发进展,以及它们目前在临床应用上的缺陷及相应的修饰或改造途径进行了阐述。结果与结论 与现有药物比较,GLP-1及其类似物药物对2型糖尿病有着显著的疗效,在糖尿病治疗领域有广泛的应用前景。     

胰高血糖素样肽-1类似物的研究进展

该文主要介绍了近年来成为糖尿病治疗领域研究热点的胰高血糖素样肽-1(GLP-1)类似物的治疗药物及其临床研究应用进展.随着人们对GLP-1类似物及其治疗药物的进一步认识以及深入研究,将有望开发出更多治疗糖尿病的新型药物应用于临床,造福于广大患者.     

胰高血糖素样肽-1及其类似物的生物学活性测定方法

胰高血糖素样肽-1(GLP-1)因其独特的生理功能成为治疗2型糖尿病最有潜力的药物之一,有很好的开发前景。本文对GLP-1及其类似物的生物学活性,如稳定性、免疫学活性、体外和体内生物学活性的测定方法进行了综述,为GLP-1及其类似物的应用开发研究提供参考。     

胰高血糖素样肽1及其类似物治疗2型糖尿病的研究进展

目的:了解胰高血糖素样肽1(GLP-1)及其类似物治疗2型糖尿病的研究进展,为2型糖尿病的药物治疗提供参考。方法:查阅近年来国内外相关文献,就GLP-1及其类似物治疗2型糖尿病的研究进行归纳和总结。结果与结论:GLP-1类似物在2型糖尿病的治疗中使用广泛,其能促进葡萄糖依赖的胰岛素分泌,抑制胰高血糖素的合成,有效改善血糖水平。同时,GLP-1类似物还能够抑制机体餐后胃排空,减少热量摄入,减轻患者体质量。现有的GLP-1类似物中,艾塞那肽降血糖效果明显,患者依从性差,且存在恶心呕吐等不良反应;利拉鲁肽能很好地控制血糖,但存在胃肠道反应;阿必鲁肽降糖效果不及利拉鲁肽;度拉糖肽疗效与利拉鲁肽相当,是最具潜力的2型糖尿病治疗药物;利司那肽在美国还未被批准上市,但具有较好的临床应用前景。     

糖尿病治疗新药——长效化胰高血糖素样肽-1（GLP-1）及其类似物的研究进展

胰高血糖素样肽-1（GLP-1）是机体在响应营养摄入时而释放的一类肠促胰岛素,主要由肠道末端内分泌L细胞分泌。GLP-1具有降糖作用．同时在治疗2型糖尿病可取得理想的效果。但是,GLP-1在体内不稳定,易被二肽基肽酶Ⅳ（DPPⅣ）迅速降解,并迅速被肾脏清除。其半衰期很短。因此,长效化GLP-1及其类似物成为目前抗糖尿病研究的热点之一。本文分别综述了几类长效GLP-1及其类似物和与之相关的降糖作用。     

利拉鲁肽的药理及临床研究进展

 利拉鲁肽是一种酰化胰高血糖素样肽-1（GLP-1）类似物,通过激活GLP-1受体,以葡萄糖依赖性刺激胰岛素分泌并抑制胰高血糖素分泌,临床用于2型糖尿病的二线治疗,可与其他口服降糖药联合使用,但不用于1型糖尿病的治疗。文中通过Medline对利拉鲁肽进行文献检索,并对其药理作用、药动学、临床研究、安全性和药物相互作用等进行综述。     

利拉鲁肽和阿必鲁泰治疗2型糖尿病临床研究进展

利拉鲁肽和阿必鲁泰是治疗2型糖尿病的新靶点药物,较已有的口服降糖药降糖效果好、副作用较小,而且可以减轻体质量,因此有广阔的应用前景。作为新一代降糖新药,利拉鲁肽是一种短效胰高血糖素样肽-1（GLP-1）类似物,阿必鲁泰是一种长效GLP-1类似物,两者既有共同之处,又有区别。总结这二种抗糖尿病新药的临床应用和不良反应研究进展,为临床合理用药以及新药研发提供思路。     

从循证证据看德谷胰岛素利拉鲁肽注射液的临床应用

基础胰岛素与胰高血糖素样肽-1受体激动剂（glucagon-like peptide-1 receptor agonist,GLP-1RA）联合用药是近十年糖尿病注射疗法的重要进展之一。新型降糖药物德谷胰岛素利拉鲁肽注射液（Insulin Degludec and Liraglutide Injection,IDegLira）将基础胰岛素类似物（德谷胰岛素）与GLP-1RA受体激动剂（利拉鲁肽）两种药物联合,2022年进入中国市场。现依据IDegLira发表的相关循证证据,介绍作用机制、药效/药代动力学,并且从循证医学角度列举在不同2型糖尿病人群的疗效和安全性及其真实世界研究结果,以帮助临床医生全面了解IDegLira。     

胰高血糖素样肽-1及其类似物的研究进展

目的介绍胰高血糖素样肽-1(GLP-1)及其类似物的结构特点、研究进展以及临床情况。方法查阅国内外文献及相关资料,根据GLP-1的结构特点,归纳了对其进行的结构改造与修饰的方法及所产生的临床药效。结果 GLP-1能葡萄糖浓度依赖地促进胰岛素分泌,能降低2型糖尿病患者糖化血红蛋白水平和餐后血糖,并能减轻体质量。结论通过对GLP-1的结构改造与修饰,开发更稳定更有效的GLP-1类似物,是未来糖尿病治疗领域的主要研究思路之一。     

利拉鲁肽单药治疗长期安全有效——LEAD-3及扩展研究浅析

新一代基于肠促胰素的降糖药物，利拉鲁肽——每日一次的人胰高糖素样肽-1（GLP-1）类似物，面世后便得到医学界广泛关注。近来“利拉鲁肽对糖尿病的疗效与作用”（LEAD，Liraglutide Effectand Actionin Diabetes）系列临床研究结果在国外权威学术期刊相继发表，其中，LEAD-3及其扩展研究，对利拉鲁肽和格列美脲单药治疗比较显示出利拉鲁肽单药治疗在疗效和安全性上的优势，为2型糖尿病的临床治疗带来了新希望。     

胰高血糖素样肽1类似物治疗糖尿病国内研究现状

目的系统评价肠促胰素类药物胰高血糖素样肽1(GLP-1)受体激动剂治疗糖尿病在国内的研究现状,了解其未来发展趋势。方法计算机检索中国知网(CNKI)、维普网(VIP)、万方数据库,搜集相关研究,检索时间为自建库至2018年12月31日。根据纳入和排除标准对检索到的文献进行筛选,对纳入研究采用文献计量分析法对其发表时间、发表期刊、研究类型及研究药物品种进行分析,并对我国GLP-1类似物治疗糖尿病研究热点内容进行定性分析。结果共纳入文献2137篇,1995年至2015年的发文数量一直呈增长趋势,2015年至2018年趋于稳定,维持在320篇左右;研究类型发文量由高到低依次为临床研究,综述,动物试验和药理研究,药物合成、制备及分析研究。药物专利及市场研究,药物利用和药物经济学研究,药代动力学研究。结论目前,国内GLP-1类似物治疗糖尿病的研究重点为临床疗效研究,虽然GLP-1类似物治疗糖尿病有显著优势,但其价格比传统降糖药(MET,SU,TZD,AGI等)高,关于GLP-1类似物的经济性探索将成为另一个研究重点,这将在一定程度上决定GLP-1类似物能否在临床广泛使用。     

胰高血糖素样肽-1及类似物的降压作用研究进展

胰高血糖素样肽-1是体内一种重要的肠促胰岛素,具有葡萄糖浓度依赖性降糖作用,其类似物已用于2型糖尿病治疗。近年来的临床前和临床研究均发现胰高血糖素样肽-1及类似物有一定程度的降压作用,其作用机制可能与促进水钠排泄、改善血管内皮功能等有关。本文综述胰高血糖素样肽-1及类似物的降压作用。     

胰高血糖素样肽-1及相关降糖药物的研究进展

胰高血糖素样肽-1（glucagon-like peptide-1,GLP-1）是近几年糖尿病治疗药物研究的热点之一,具备多重降血糖作用。它的两大类药物：GLP-1类似物和二肽基肽酶-Ⅳ抑制剂作为新的降糖药物相继完成临床研究,并在糖尿病治疗中发挥越来越重要的作用。本文就GLP-1的结构、药理作用以及两类相关降糖药物的临床应用作一概述。     

人GLP-1类似物治疗2型糖尿病的研究进展

人胰高血糖素样肽1（GLP-1）类似物已成为新一代降糖药。无论是上市的艾塞那肽和利拉鲁肽,还是处于临床研究阶段的taspoglutide,均在2型糖尿病临床研究中取得显著成果,如有效降糖、减轻体重和减少低血糖发生等。同时,人GLP—1类似物潜在的益处与风险还有待进一步研究。     

Glucagon-like peptide 1 and inhibitors of dipeptidyl peptidase IV in the treatment of type 2 diabetes mellitus

Proof-of-concept for the efficacy of a glucagon-like peptide 1 (GLP-1)-based therapy of patients with type 2 diabetes was provided in 2002 by means of prolonged continuous subcutaneous infusion of native GLP-1. Since then, several long-acting analogues of GLP-1, as well as inhibitors of dipeptidyl peptidase IV, the enzyme that rapidly inactivates endogenous GLP-1, have demonstrated efficacy in long term clinical trials.     

Inhibitors of dipeptidyl peptidase IV--recent advances and structural views

Prevalence of type 2 diabetes has increased dramatically in the last decades. Current medicines are not yet capable to efficiently prevent or reverse progression of the disease and its associated comorbidities. As a consequence, there is a great need for novel antidiabetic drugs. Treatments of type 2 diabetes that are based on enhanced and sustained action of insulinotropic incretin hormones such as GLP-1 have received much attention in the past years. Treatment strategies include administration of: 1) GLP-1 analogues that are resistant to degradation by the serine protease DPP-IV, and 2) small molecule DPP-IV inhibitors that are able to provide sustained action of endogenous GLP-1, again by preventing its degradation. This review summarizes recent research results for the second approach. It briefly touches upon the advantages that treatment of type 2 diabetes with DPP-IV inhibitors may offer over current medications. In the main section, several important structural classes of DPP-IV inhibitors are described and compared based on literature data. Specific attention is given to the analysis of several X-ray structures of enzyme-inhibitor co-crystals. Finally, as clinical data are steadily emerging for some of the most advanced development candidates, the last section of this review is providing a brief overview of some efficacy data from recent clinical studies with DPP-IV inhibitors.     

胰高血糖素样肽1类似物治疗2型糖尿病的安全性与耐受性

目的:介绍以艾塞那肽及利拉鲁肽为代表的胰高血糖素样肽1(GLP-1)类似物在治疗2型糖尿病过程中的安全性与耐受性.方法:在多项临床及动物实验的基础上,对GLP-1类似物的安全性与耐受性进行归纳总结.结果与讨论:GLP-1类似物的安全性与耐受性问题包括低血糖事件及胃肠道副反应的发生率,肝肾功能不全患者用药剂量是否需要调整,以及该药与急性胰腺炎、甲状腺C细胞增生或肿瘤的相关性等问题尚待更加深入的研究证实,临床医生在治疗2型糖尿病的过程中,应严格掌握用药指征,密切观察病人胃肠道症状体征及肝肾功能相关指标,合理用药.     

Gut peptides in the treatment of diabetes mellitus

It has been known for at least one century that agents secreted from the intestine during meal absorption regulates glucose assimilation. Extensive research during the past three decades has identified two gut hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP, also known as gastric inhibitory polypeptide) that are important in postprandial glucose metabolism. Both peptides are incretins; they are secreted during carbohydrate absorption and increase insulin secretion. Since they are potent insulin secretagogues, GIP and GLP-1 have received considerable attention as potential diabetes therapeutics. However, only GLP-1 exerts insulinotropic properties when administered to patients with Type 2 diabetes. Both GLP-1 and GIP are rapidly inactivated in the circulation by the enzyme dipeptidyl peptidase IV (DPP-IV). The application of GLP-1 into clinical practice has been delayed due to the need to develop compounds that overcome this rapid inactivation. Two approaches have been taken to utilise the insulinotropic and glucose-lowering actions of GLP-1 as an antidiabetic agent: the development of DPPIV-resistant analogues and the inhibition of DPP-IV. This review focuses on the physiology of GLP-1 and GIP and the advances that have been made thus far in developing treatments based on these physiological incretins for Type 2 diabetes.     

肠促胰岛素激素类2-型糖尿病药物研究进展

近年来糖尿病患者递增,糖尿病已经成为严重危害人类健康的疾病。新型2-型糖尿病药物的研发已成为当前药物研究的一大热点。研究表明葡萄糖依赖性促胰岛素分泌多肽（glucose-dependent-insulinotropie polypeptide,GIP）和胰高血糖素样肽-1（glucagons like peptide-1.GLP-1）是人类重要的肠促胰岛素激素,GLP-1和GIP对于保持人体葡萄糖稳态平衡意义重大。目前根据GLP-1和GIP的作用机制研发出胰高血糖素样肽-l类似物和受体激动剂以及二肽基肽酶-4（DPP-4）抑制剂,均具有广阔的临床价值及市场前景。     

Gut peptides in the treatment of diabetes mellitus

It has been known for at least one century that agents secreted from the intestine during meal absorption regulates glucose assimilation. Extensive research during the past three decades has identified two gut hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP, also known as gastric inhibitory polypeptide) that are important in postprandial glucose metabolism. Both peptides are incretins; they are secreted during carbohydrate absorption and increase insulin secretion. Since they are potent insulin secretagogues, GIP and GLP-1 have received considerable attention as potential diabetes therapeutics. However, only GLP-1 exerts insulinotropic properties when administered to patients with Type 2 diabetes. Both GLP-1 and GIP are rapidly inactivated in the circulation by the enzyme dipeptidyl peptidase IV (DPP-IV). The application of GLP-1 into clinical practice has been delayed due to the need to develop compounds that overcome this rapid inactivation. Two approaches have been taken to utilise the insulinotropic and glucose-lowering actions of GLP-1 as an antidiabetic agent: the development of DPP-IV-resistant analogues and the inhibition of DPP-IV. This review focuses on the physiology of GLP-1 and GIP and the advances that have been made thus far in developing treatments based on these physiological incretins for Type 2 diabetes.