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。     

GLP-1的药理活性研究

胰高血糖素样肽1(GLP-1)是一种肠肽激素,主要由末端空肠、回肠和结肠的L细胞所分泌。大量动物试验和临床研究表明,GLP-1能明显降低2型糖尿病患者的空腹和餐后血糖,本课题组基于GLP-1的降糖机制,根据统计分析结果判断GLP-1的药理活性。     

2型糖尿病治疗新药-利拉鲁肽最新研究结果公布

药物LEAD项目是人胰高糖素样肽1（GLP－1）类似物利拉鲁肽（liraglutide）的大规模、全球多中心Ⅲ期临床研究,共纳入4000多例2型糖尿病患者,探索了利拉鲁肽单药、与口服降糖药联用及与同类药物相比较的疗效和安全性。随着LEADl～6研究结果的陆续公布,相关荟萃分析也不断开展,其结果表明,利拉鲁肽不但可以有效降糖,而且可减轻体重,低血糖风险小,     

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。     

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。     

胰高血糖素样肽-1研究概况

肠促胰素已成为治疗2型糖尿病的热点。胰高血糖素样肽-1具有促进胰岛素合成和分泌、抑制胰高血糖素分泌、促进胰岛B细胞增殖的生理功能。此外,胰高血糖素样肽。1还具有延缓胃排空、抑制食欲和调节脂肪代谢等功能。艾塞那肽和利拉鲁肽是目前临床应用较多的胰高血糖素样肽-1类似物,临床研究证实其能有效降低血糖、糖化血红蛋白水平及体重指数且无低血糖反应,为2型糖尿病患者治疗带来了新的希望。胰高血糖素样肽-1类似物也存在一定的不良反应,其长期安全性有待进一步观察研究。     

GLP-1类似物利拉鲁肽研究进展

胰高糖素样肽-1类似物(GLP-1类似物)利拉鲁肽是一种全新作用机制的降糖药物,具有降低体重、降低收缩压、改善胰岛细胞功能.本文对利拉鲁肽国内外近期文献进行分析,从其药理作用特点、临床研究、安全性和耐受性等方面阐述其研究进展.其长期应用疗效如何以及能否延缓糖尿病的进展仍需要进一步的研究.     

司美格鲁肽临床和安全性的研究进展

司美格鲁肽作为新型的人胰高血糖素样肽-1受体激动剂,在国内用于2型糖尿病的治疗,其独特药物特性赋予其在血糖控制、体质量管理和胰岛素抵抗改善等方面显著效果。近年临床研究进一步揭示其在降低心血管事件、代谢相关脂肪性肝炎、癌症免疫治疗和神经退行性疾病等领域的潜力。然而,应用司美格鲁肽也伴随一些新风险,如胆囊疾病和延迟胃排空带来的临床隐忧。汇总最新研究成果,全面评估司美格鲁肽在各领域的疗效和安全性,旨在为其更广泛的临床应用提供指导。     

2型糖尿病治疗药物杜拉鲁肽的研究进展

杜拉鲁肽是一种长效胰高血糖素样肽-1(GLP-1)受体激动剂,能促进胰岛素分泌,保护胰岛β细胞,抑制胰高血糖素分泌,抑制胃排空,降低食欲;临床用于2型糖尿病(T2DM)和肥胖症的治疗;本品不适用于1型糖尿病,也不能替代胰岛素治疗。本文综述了近年来杜拉鲁肽的研究文献,从作用机制、药效学和药动学、临床研究、不良反应等方面介绍GLP-1受体激动剂杜拉鲁肽的研究进展,旨在为临床合理用药提供参考。     

胰激肽释放酶治疗糖尿病视网膜病变的系统评价

目的：评价胰激肽释放酶治疗糖尿病视网膜病变的疗效与安全性。方法：检索MEDLINE（1977～2008）、EMBASE（1989～2008）、Cochrane临床试验数据库、CBMdisc（1978～2008）和CNKI（1979～2008）等文献数据库，收集胰激肽释放酶治疗糖尿病视网膜病变的临床研究，进行质量评价，并对符合纳入标准的临床研究进行Meta分析。结果：共纳入4项随机、对照研究，全部为中文，未检索到关于此题目的其他语种研究报告。4项研究的质量均较低，4项研究Juni评分为C级。所有研究均未对远期效果进行评价。有1项研究未提到随机分组，其他3项研究提到采用随机分组，但未描述具体的随机方法，未进行分配方案的隐藏。所有研究均未使用盲法，也未进行随访。由于缺乏高质量的临床研究，上述Meta分析未进行敏感性分析。结论：胰激肽释放酶可能对糖尿病视网膜病有一定的疗效。由于目前的临床研究质量较低，且未对远期疗效进行评价，胰激肽释放酶对于糖尿病视网膜病变的疗效还需要进行大规模及高质量的随机对照研究加以证实。     

Effects of glucagon-like peptide-1 and long-acting analogues on cardiovascular and metabolic function

Although the insulinotropic role of glucagon-like peptide-1 (GLP-1) in type 2 diabetes mellitus has been substantiated, its role in cardioprotection remains largely unknown. To ascertain the role of the cardiovascular actions of GLP-1 in health and disease states necessitates a review of the current evidence as well as ongoing investigation. Of cardiovascular significance, both positive inotropic and chronotropic effects, unmodifiable by beta-adrenergic blockers, have been reportedly attributed to GLP-1 actions on the myocardium. However, the potent role of GLP-1 and its analogues in eliciting tachycardic and pressor effects should be of some concern. Aside from its reported insulinotropic activity, GLP-1 impacts the myocardium directly. Highly specific GLP-1 receptors have been identified in the heart and within the central nervous system, particularly in the nucleus tractus solitarius, a neuromodulatory centre of cardiovascular control. The occurrence of GLP-1 receptors in cardiac tissue and autonomic regions of cardiovascular control has stimulated investigation, particularly as these sites may be suitable targets for the pharmacological action of GLP-1 and long-acting analogues. Discordance on the haemodynamic consequences of GLP-1 pharmacotherapy in experimental animals and human patients has been reported in the literature. However, long-term pharmacological doses of GLP-1 have shown prolonged and beneficial actions on cardiovascular homeostasis in the adjuvant treatment of metabolic disease.     

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。     

The novel use of GLP-1 analogue and insulin combination in type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a global public health problem. Due to the progressive nature of the disease, a combination(s) of two or more drugs acting on different pathophysiological process is often necessary to achieve early and sustained achievement of individualized glycemic targets. At the same time, choosing the safest option to avoid hypoglycemia is of paramount importance. GLP-1 analogues are a relatively recent class of anti-diabetic drugs, and are highly effective with an acceptable safety profile. Attempts have been made to combine GLP-1 analogues with basal insulin for management of T2DM. Presently GLP-1 analogues like exenatide/long acting exenatide and liraglutide have been co-administered with basal insulin like glargine and detemir respectively, and are approved by regulatory agencies. Currently a fixed dose combination (FDC) of insulin degludec and liraglutide is under development. GLP-1 analogue and insulin as FDC or by co-administration, is a rational method of controlling fasting and postprandial glucose effectively. The efficacy and safety of this combination has been studied in a wide population with promising outcomes. Innovative use of GLP-1 analogues beyond diabetes is also being attempted, and a variety of patents are filed or granted for the same. This review summarizes the current status of GLP-1 and insulin combination in the management of T2DM and highlights the new frontiers in research involving GLP-1. Patents on combination of GLP-1 and insulin which were granted earlier, and the ones which have been applied for, are also discussed.     

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。     

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。     

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.     

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。     

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.     

Targeting amyloid-beta by glucagon-like peptide -1 (GLP-1) in Alzheimer's disease and diabetes

INTRODUCTION: Epidemiological evidence suggests an association between type 2 diabetes (T2DM) and Alzheimer's disease (AD), in that one disease increases the risk of the other. T2DM and AD share several molecular processes which underlie the tissue degeneration in either disease. Disturbances in insulin signaling may be the link between the two conditions. Drugs originally developed for T2DM are currently being considered as possible novel agents in the treatment of AD. AREAS COVERED: This review discusses the potential role of glucagon-like peptide -1 (GLP-1) treatment in AD. GLP-1 receptors are expressed in areas of the brain important to memory and learning, and GLP-1 has growth-factor-like properties similar to insulin. A key neuropathological feature of AD is the accumulation of amyloid-beta (Aβ). In preclinical studies, GLP-1 and longer lasting analogues have been shown to have both neuroprotective and neurotrophic effects, and to protect synaptic activity in the brain from Aβ toxicity. EXPERT OPINION: A convincing amount of evidence has shown a beneficial effect of GLP-1 agonist treatment on cognitive function, memory and learning in experimental models of AD. GLP-1 analogues may therefore be the new therapeutic agent of choice for intervention in AD.