Small-Molecule Glp-1 Secretagogs: Challenges And Recent Advances

Glucagon-like peptide-1 (GLP-1) is a potent anti-hyperglycemic 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.