Advances in small-molecule insulin secretagogues for diabetes treatment
Jingqian Su, Jingran Xu, Shan Hu, Hui Ye, Lian Xie, Songying Ouyang
Abstract
Diabetes, a metabolic disease caused by abnormally high levels of blood glucose, has a high prevalence rate worldwide and causes a series of complications, including coronary heart disease, stroke, peripheral vascular disease, end-stage renal disease, and retinopathy. Small-molecule compounds have been developed as drugs for the treatment of diabetes because of their oral advantages. Insulin secretagogues are a class of small-molecule drugs used to treat diabetes, and include sulfonylureas, non-sulfonylureas, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase 4 inhibitors, and other novel small-molecule insulin secretagogues. However, many small-molecule compounds cause different side effects, posing huge challenges to drug monotherapy and drug selection. Therefore, the use of different small-molecule drugs must be improved. This article reviews the mechanism, advantages, limitations, and potential risks of small-molecule insulin secretagogues to provide future research directions on small-molecule drugs for the treatment of diabetes. • Small-molecule insulin secretagogues offer effective diabetes treatment options. • Targets to promote insulin secretion include GPCRs, DPP-4 and PTP1B. • Small-molecule drugs for different targets have different efficacies. • For fewer side effects, different drugs and delivery modes should be selected. • Future focus: optimizing drug structures for better targeting and efficacy.