Glucagon-like peptide-1 (GLP-1) is a potent antihyperglycemic hormone that is an alternative treatment choice for patients with type 2 diabetes mellitus (T2DM). The glucose-dependent mechanism of GLP-1 is particularly important because it does not stimulate insulin secretion and cause hypoglycemia when plasma glucose concentrations are in the normal fasting range. Although several peptide drugs of GLP-1 analogs are clinically available, research on the small molecules that stimulate GLP-1 secretion is still struggling. In this review, we summarize recent updates in the discovery of small-molecule GLP-1 secretagogs targeting the G-protein-coupled receptor (GPCR) family. we also discuss the challenges and strategies for the study and describe the latest developments.

胰高血糖素样肽1（GLP-1）是一种有效的降血糖激素，是2型糖尿病（T2DM）患者的另一种治疗选择。GLP-1的葡萄糖依赖性机制特别重要，因为当血浆葡萄糖浓度在正常的禁食范围内时，它不会刺激胰岛素分泌并引起低血糖症。尽管临床上可以买到几种GLP-1类似物的肽类药物，但对刺激GLP-1分泌的小分子的研究仍在努力。在这篇综述中，我们总结了针对G蛋白偶联受体（GPCR）家族的小分子GLP-1分泌蛋白的最新进展。我们还将讨论这项研究的挑战和策略，并描述最新发展。