Alogliptin is a dipeptidyl-peptidase IV (DPP-4) inhibitor that was
approved in Japan in 2010 for treatment of type 2 diabetes, a disease in
which insulin resistance and β-cell dysfunction lead to hyperglycemia.
As islet function is lost, the severity of insulin resistance
increases. The introduction of DPP-4 inhibitors has brought a novel
class of insulinotropic agents for the treatment options available to type
2 diabetic patients. The therapeutic potential of glucagon-like peptide 1
(GLP-1), an incretin peptide, for the treatment of type 2 diabetes was
realized in the 1990s. The insulinotropic effects of GLP-1 depend closely
on glucose concentrations providing the possibility of glucose normalization
without the risk of hypoglycemia. GLP-1 has other non-insulinotropic
physiological actions that are advantageous. It suppresses glucagon
secretion from a cells and slows gastric emptying, which contributes to
satiety and to a slower passage and reabsorption of carbohydrates. GLP-1
also contributes to satiety via a central mechanism as a neurotransmitter
with effects on the hypothalamus.
Syrrx Inc. (now Takeda San Diego) (Japan)
Alogliptin is an oral antihyperglycemic agent that is a selective inhibitor of the enzyme dipeptidyl peptidase-4 (DPP-4).
Antidiabetic agent.
ChEBI: A piperidine that is 3-methyl-2,4-dioxo-3,4-dihydropyrimidine carrying additional 2-cyanobenzyl and 3-aminopiperidin-1-yl groups at positions 1 and 2 respectively (the R-enantiomer). Used in the form of its benzoate salt for treatment of t
pe 2 diabetes.
Dipeptidyl peptidase 4 inhibitor:
Treatment of type 2 diabetes in combination with
other therapies
Alogliptin does not undergo extensive metabolism. Two
minor metabolites were detected following administration
of an oral dose of [14C]-alogliptin, N-demethylated
alogliptin, M-I (<1% of the parent compound), and
N-acetylated alogliptin, M-II (<6% of the parent
compound). M-I is an active metabolite and is a highly
selective inhibitor of DPP-4 similar to alogliptin; M-II
does not display any inhibitory activity towards DPP-4
or other DPP-related enzymes. In vitro data indicate
that CYP2D6 and CYP3A4 contribute to the limited
metabolism of alogliptin.
