Advances in small-molecule insulin secretagogues for diabetes treatment

Biomed Pharmacother. 2024 Sep:178:117179. doi: 10.1016/j.biopha.2024.117179. Epub 2024 Jul 26.

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.

Keywords: DPP-4 inhibitor; GLP-1 receptor agonist; GPCR agonist; Insulin secretagogue; Small-molecule drugs; Type 2 diabetes.

Publication types

  • Review

MeSH terms

  • Animals
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Diabetes Mellitus / drug therapy
  • Diabetes Mellitus / metabolism
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / metabolism
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use
  • Glucagon-Like Peptide-1 Receptor / metabolism
  • Glucagon-Like Peptide-1 Receptor Agonists
  • Humans
  • Hypoglycemic Agents* / pharmacology
  • Hypoglycemic Agents* / therapeutic use
  • Insulin Secretagogues
  • Insulin Secretion / drug effects
  • Insulin* / metabolism
  • Secretagogues / pharmacology
  • Secretagogues / therapeutic use
  • Sulfonylurea Compounds / pharmacology
  • Sulfonylurea Compounds / therapeutic use

Substances

  • Hypoglycemic Agents
  • Insulin
  • Sulfonylurea Compounds
  • Dipeptidyl-Peptidase IV Inhibitors
  • Secretagogues
  • Blood Glucose
  • Glucagon-Like Peptide-1 Receptor
  • Insulin Secretagogues
  • Glucagon-Like Peptide-1 Receptor Agonists