Authors: Salvatore, Teresa; Carbonara, Ornella; Cozzolino, Domenico; Torella, Roberto; Sasso, Ferdinando C.

Source: Current Diabetes Reviews, Volume 5, Number 2, May 2009 , pp. 92-101(10)

Publisher: Bentham Science Publishers

Abstract:

Glucagon-like peptide-1 (GLP-1) is a gut hormone that plays an important role in regulating glucose homeostasis by both its pancreatic and extrapancreatic activity. Defects of GLP-1 characterize type 2 diabetes as a primary or perhaps consequent phenomenon, resulting in inappropriately low insulin secretion after oral ingestion of nutrients. The discovery that cleavage by the ubiquitous enzyme dipeptidyl peptidase-IV (DPP-IV) is the primary route of GLP-1 metabolism formed the rationale behind the proposal to prevent degradation of endogenously released GLP-1 by DPP-IV inhibition as a novel approach to the management of type 2 diabetes. Enhanced insulin secretion as well as delayed gastric emptying, reduced glucagon secretion, and inhibited apoptosis of beta cells resulting from blockade of incretin degradation, have been proposed as the major actions of DPP-IV inhibitors as antidiabetic agents. Clinical studies to date indicate that DPP-IV inhibitors effectively ameliorate islet dysfunction and improve glucose control in patients with type 2 diabetes. They appear to have excellent therapeutic effectiveness as monotherapy in patients inadequately controlled with diet and exercise and as add-on therapy in combination with metformin, thiazolidinediones, and insulin. Their pharmacokinetic and pharmacodynamic profiles support once-daily dosing, with relatively few adverse effects.

Document Type: Research article

DOI: http://dx.doi.org/10.2174/157339909788166819

Publication date: 2009-05-01

More about this publication?

• Current Diabetes Reviews publishes frontier reviews on all the latest advances on diabetes and its related areas e.g. pharmacology, pathogenesis, complications, epidemiology, clinical care, and therapy.
  
  The journal's aim is to publish the highest quality review articles dedicated to clinical research in the field. The journal is essential reading for all researchers and clinicians who are involved in the field of diabetes.

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