基于胰高血糖素样肽-1的多重受体激动剂的研究进展

Research Progress on Multi-receptor Agonists Based on Glucagon-like Peptide-1

胰高血糖素样肽-1(GLP-1)受体激动剂因其独特的作用优势,在降糖及减重领域的市场份额越来越大。但由于肥胖及2型糖尿病等异质性及并发性的病理学特点,以及能量平衡调节的复杂性,其减重效果无法达到预期标准。以GLP-1为基础的单分子多重受体激动剂有望将几种胃肠激素的有益作用整合到同一个分子中,以改善代谢紊乱。在总结市场上各种GLP-1类似物的分子结构及临床表现的基础上,着重介绍各类以GLP-1为基础的单分子多靶向激动剂的研究进展,为治疗肥胖和糖尿病提供新的思路。

Glucagon-like peptide-1(GLP-1)receptor agonists account for an increasing proportion of the market of anti-diabetic and weight-reducing medicines with its unique advantages.However,due to the heterogeneity and concomitant pathological features of obesity and type 2 diabetes as well as the complexity of energy balance regulation,its moderate weight-reducing effect cannot achieve the desired results.Single-molecule multi-receptor agonists based on GLP-1 are expected to improve metabolic disorders by integrating the beneficial effects of several gut hormones.On the basis of the molecular structures and clinical data of GLP-1 analogues on the market,this review focuses on the research progress of various GLP-1-based single-molecule multi-target agonists to provide new approaches to the maintenance of blood sugar homeostasis and anti-obesity therapies.