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Incretin‐based treatment of type 2 diabetes: glucagon‐like peptide‐1 receptor agonists and dipeptidyl peptidase‐4 inhibitors *
Author(s) -
Deacon Carolyn F.
Publication year - 2007
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/j.1463-1326.2007.00765.x
Subject(s) - vildagliptin , incretin , exenatide , medicine , endocrinology , sitagliptin , liraglutide , glucagon like peptide 1 , gastric emptying , type 2 diabetes , sitagliptin phosphate , dipeptidyl peptidase , gastric inhibitory polypeptide , insulin , glucagon , diabetes mellitus , chemistry , biochemistry , stomach , enzyme
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.