Medicinal chemistry and applications of incretins and DPP-4 inhibitors in the treatment of type 2 diabetes mellitus

Mohamed Lotfy, Jaipaul Singh, Huba Kalász, Kornelia Tekes, Ernest Adeghate

Research output: Contribution to journalReview article

22 Citations (Scopus)

Abstract

Diabetes mellitus (DM) is a major metabolic disorder currently affecting over 200 million people worldwide. Approximately 90% of all diabetic patients suffer from Type 2 diabetes mellitus (T2DM). The world's economy coughs out billions of dollars annually to diagnose, treat and manage patients with diabetes. It has been shown that the naturally occurring gut hormones incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP- 1) can preserve the morphology and function of pancreatic beta cell. In addition, GIP and GLP-1 act on insulin receptors to facilitate insulin-receptor binding, resulting in optimal glucose metabolism. This review examines the medicinal chemistry and roles of incretins, specifically, GLP-1 and drugs which can mimic its actions and prevent its enzymatic degradation. The review discussed GLP-1 agonists such as exenatide, liraglutide, taspoglutide and albiglutide. The paper also identified and reviewed a number of inhibitors, which can block dipeptidyl peptidase 4 (DPP-4), the enzyme responsible for the rapid degradation of GLP-1. These DPP-4 inhibitors include sitagliptin, saxagliptin, vildagliptin and many others which are still in the experimental phase.

Original languageEnglish
Pages (from-to)82-92
Number of pages11
JournalOpen Medicinal Chemistry Journal
Volume5
Issue numberSPEC. ISSUE 2
DOIs
Publication statusPublished - Nov 9 2011

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Keywords

  • DPP-4 inhibitors
  • Incretins
  • Medicinal chemistry
  • Type 2 diabetes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery

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