Zhang Tingting, Liu Sainan, He Suning, Shi Linqi, Ma Rujiang
Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, 300071, Tianjin, China.
Chembiochem. 2025 Apr 14;26(8):e202400962. doi: 10.1002/cbic.202400962. Epub 2025 Jan 10.
Diabetes is a metabolic disorder characterized by insufficient endogenous insulin production or impaired sensitivity to insulin. In recent years, a class of incretin-based hypoglycemic drugs, glucagon-like peptide-1 receptor agonists (GLP-1RAs), have attracted great attention in the management of type 2 diabetes mellitus (T2DM) due to their benefits, including stable glycemic control ability, a low risk of hypoglycemia, and weight reduction for patients. However, like other peptide drugs, GLP-1RAs face challenges such as instability, susceptibility to enzymatic degradation, and immunogenicity, which severely limit their clinical application. In recent years, various strategies have been developed to improve the bioavailability and therapeutic efficacy of GLP-1RAs, including structural modification and carrier-mediated delivery. This article briefly introduces the research and application status of several common GLP-1RAs and their limitations. Taking exendin-4 as an example, we focus on the research progress of improving bioavailability and therapeutic efficacy based on structural modification and carrier delivery strategies, aiming to provide reference for the development of new GLP-1RAs treatment systems.
糖尿病是一种代谢紊乱疾病，其特征为内源性胰岛素分泌不足或对胰岛素的敏感性受损。近年来，一类基于肠促胰岛素的降糖药物，即胰高血糖素样肽-1受体激动剂（GLP-1RAs），因其具有稳定的血糖控制能力、低血糖风险低以及能使患者体重减轻等益处，在2型糖尿病（T2DM）的管理中备受关注。然而，与其他肽类药物一样，GLP-1RAs面临着诸如稳定性差、易受酶降解以及免疫原性等挑战，这些严重限制了它们的临床应用。近年来，已开发出各种策略来提高GLP-1RAs的生物利用度和治疗效果，包括结构修饰和载体介导递送。本文简要介绍了几种常见GLP-1RAs的研究与应用现状及其局限性。以艾塞那肽-4为例，我们重点关注基于结构修饰和载体递送策略提高生物利用度和治疗效果的研究进展，旨在为新型GLP-1RAs治疗系统的开发提供参考。
