Incretin mimetics and dipeptidyl peptidase-IV inhibitors: Potential new therapies for type 2 diabetes mellitus

Curtis Triplitt, Alison Wright, Elaine Chiquette

Research output: Contribution to journalReview article

42 Scopus citations

Abstract

The emergence of the glucoregulatory hormones glucagon-like peptide-1 (GLP-I) and glucose-dependent insulinotropic polypeptide has expanded our understanding of glucose homeostasis. In particular, the glucoregulatory actions of the incretin hormone GLP-1 include enhancement of glucose-dependent insulin secretion, suppression of inappropriately elevated glucagon secretion, slowing of gastric emptying, and reduction of food intake. Two approaches have been developed to overcome rapid degradation of GLP-1. One is the use of agents that mimic the enhancement of glucose-dependent insulin secretion, and potentially other antihyperglycemic actions of incretins, and the other is the use of dipeptidyl peptidase-IV inhibitors, which reduce the inactivation of GLP-1, increasing the concentration of endogenous GLP-1. The development of incretin mimetics and dipeptidyl peptidase-IV inhibitors opens the door to a new generation of antihyperglycemic agents to treat several otherwise unaddressed pathophysiologic defects of type 2 diabetes mellitus. We review the physiology of glucose homeostasis, emphasizing the role of GLP-1, the pathophysiology of type 2 diabetes mellitus, the clinical shortcomings of current therapies, and the potential of new therapies-including the newly approved incretin mimetic exenatide-that elicit actions similar to those of GLP-1.

Original languageEnglish (US)
Pages (from-to)360-374
Number of pages15
JournalPharmacotherapy
Volume26
Issue number3
DOIs
Publication statusPublished - Mar 1 2006

    Fingerprint

Keywords

  • AC2993
  • DPP-IV inhibitors
  • Dipeptidyl peptidase-IV inhibitors
  • Exenatide
  • GIP
  • GLP-1
  • Glucagon-like peptide-1
  • Glucose-dependent insulinotropic polypeptide
  • Incretin mimetic
  • LAF237
  • Liraglutide
  • MK-0431
  • NN2211
  • Sitagliptin
  • Type 2 diabetes mellitus
  • Vildagliptin

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this