Inhibition of dipeptidyl peptidase-4: The mechanisms of action and clinical use of vildagliptin for the management of type 2 diabetes

Galina Smushkin, Adrian Vella

Research output: Contribution to journalReview articlepeer-review

2 Scopus citations

Abstract

Postprandial hyperglycemia in type 2 diabetes is characterized by impaired insulin secretion and action, decreased glucose effectiveness and defective suppression of glucagon secretion. Newly available therapies for type 2 diabetes target the pathway of the incretin hormone glucagon-like peptide-1 (GLP-1). Oral inhibitors of dipeptidyl peptidase-4 (DPP-4) raise the level of endogenous GLP-1 by inhibiting its clearance thereby lowering fasting and postprandial glucose concentrations. Unlike compounds which act as agonists of the GLP-1 receptor, DPP-4 inhibitors are not associated with significant effects on gastrointestinal motility, which led to a controversy around the mechanisms responsible for their glucose-lowering effects. Here we review the evidence in regards to the mechanisms whereby DPP-4 inhibitors lower glucose concentrations. Their effects are most likely mediated by an increase in endogenous GLP-1, although additional mechanisms may be involved. The pharmacology, efficacy and safety of vildagliptin, a novel DPP-4 inhibitor, are also discussed.

Original languageEnglish (US)
Pages (from-to)83-90
Number of pages8
JournalDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy
Volume2
StatePublished - 2009

Keywords

  • DPP-4 inhibitor
  • Glucagon-like peptide 1
  • Incretin
  • Insulin action
  • Insulin secretion

ASJC Scopus subject areas

  • Internal Medicine
  • Pharmacology

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