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新兴的 GLP-1 受体激动剂。

Emerging GLP-1 receptor agonists.

机构信息

Diabetes Research Division , Department of Internal Medicine F, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.

出版信息

Expert Opin Emerg Drugs. 2011 Dec;16(4):607-18. doi: 10.1517/14728214.2011.616493. Epub 2011 Sep 9.

Abstract

INTRODUCTION

Recently, glucagon-like peptide-1 receptor (GLP-1R) agonists have become available for the treatment of type 2 diabetes. These agents exploit the physiological effects of GLP-1, which is able to address several of the pathophysiological features of type 2 diabetes. GLP-1R agonists presently available are administered once or twice daily, but several once-weekly GLP-1R agonists are in late clinical development.

AREAS COVERED

The present review aims to give an overview of the clinical data on the currently available GLP-1R agonists used for treatment of type 2 diabetes, exenatide and liraglutide, as well as the emerging GLP-1R agonists including the long-acting compounds.

EXPERT OPINION

An emerging therapeutic trend toward initial or early combination therapy with metformin- and incretin-based therapy is anticipated for patients with type 2 diabetes. GLP-1-based therapy has so far proven safe and tolerable. The determination of which incretin-based therapy to choose necessitates comparisons between the various GLP-1R agonists. The available GLP-1R agonists cause sustained weight loss and clinical relevant improvement of glycemic control. The long-acting GLP-1R agonists in late development may improve the effects of GLP-1 even further with optimized pharmacokinetic profiles resulting in fewer side effects. Meta-analyses have shown promising effects on cardiovascular disease and data from ongoing multicenter trials with cardiovascular endpoints are expected in 2015.

摘要

简介

最近,胰高血糖素样肽-1 受体(GLP-1R)激动剂已被用于治疗 2 型糖尿病。这些药物利用 GLP-1 的生理作用,能够解决 2 型糖尿病的多种病理生理特征。目前可获得的 GLP-1R 激动剂每天给药 1 次或 2 次,但几种每周给药 1 次的 GLP-1R 激动剂处于后期临床开发阶段。

涵盖领域

本综述旨在概述目前用于治疗 2 型糖尿病的 GLP-1R 激动剂(艾塞那肽和利拉鲁肽)的临床数据,以及新出现的 GLP-1R 激动剂,包括长效化合物。

专家意见

预计对于 2 型糖尿病患者,将出现一种新的治疗趋势,即最初或早期联合二甲双胍和肠促胰岛素治疗。基于 GLP-1 的治疗迄今为止已被证明是安全且耐受良好的。确定选择哪种肠促胰岛素治疗需要比较各种 GLP-1R 激动剂。现有的 GLP-1R 激动剂可引起持续的体重减轻和临床相关的血糖控制改善。后期开发的长效 GLP-1R 激动剂可能会通过优化的药代动力学特性进一步改善 GLP-1 的作用,从而减少副作用。荟萃分析显示对心血管疾病有良好的效果,预计 2015 年会有关于心血管终点的正在进行的多中心试验的相关数据。

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