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Incretin-based treatment of type 2 diabetes: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors*


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    Conflict of interest statement:
    C. D. has received lecture fees from Merck & Co, Novo Nordisk and Prosidion; has served on advisory boards; and has acted as a consultant for Novo Nordisk and Dainippon Sumimoto Pharma Co Ltd.
    This article is based on a presentation given by Dr D. J. Drucker at a stand-alone symposium entitled, ‘Islet enhancement through DPP-4 inhibition as a treatment strategy in prediabetes,’ which was held during the Second International Congress on ‘Prediabetes’ and the metabolic syndrome in Barcelona.

Carolyn F. Deacon, PhD, Department of Biomedical Sciences, Panum Institute, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark.


Incretins are gut peptides that potentiate nutrient-stimulated insulin secretion following meal ingestion. Activities of the dominant incretins, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide, include glucose-dependent stimulation of insulin secretion and, in preclinical models, improvement in islet β-cell mass. GLP-1 additionally reduces glucagon secretion, inhibits gastric emptying and promotes satiety. Patients with type 2 diabetes mellitus (T2DM) exhibit reduced total and intact GLP-1 levels, and exogenous administration of the hormone via continuous infusion results in glucose profiles similar to those in non-diabetic subjects. Incretins are rapidly degraded by dipeptidyl peptidase-4 (DPP-4). Thus, strategies to enhance incretin activity have included development of GLP-1 receptor agonists resistant to the action of DPP-4 (e.g. exenatide and liraglutide) and DPP-4 inhibitors that act to increase concentrations of endogenous intact incretins (e.g. sitagliptin and vildagliptin). Clinical trials of these incretin-based therapies have shown them to be effective in improving glycaemic control in patients with T2DM.