Sitavia Mechanism of Action

Pharmacology: Pharmacodynamics: Sitagliptin inhibits dipeptidyl peptidase-4 (DPP-4), an enzyme that inactivates glucagon-like peptide (GLP-1) and glucose dependent insulinotropic polypeptide (GIP), which are incretin hormones. The drug inhibits DPP-4 selectively with no effect on DPP-8 or DDP-9 in vitro at concentrations approximating those from therapeutic dosage. Sitagliptin increases circulating concentrations of GIP and GLP-1 in a glucose-dependent manner.
GIP and GLP-1 stimulate insulin synthesis and release from pancreatic B-cells in a glucose-dependent manner. GLP-1 also decreases glucagon secretion from pancreatic alpha-cells in a glucose-dependent manner, leading to reduced hepatic glucose production.
Sitagliptin lowers fasting plasma glucose concentrations and reduces glucose excursions following glucose load or meal in patients with type 2 diabetes mellitus.
Pharmacokinetics: Peak plasma sitagliptin concentration is achieved within 3 hours following oral administration. Absolute bioavailability is approximately 87%. Administration of sitagliptin with a high-fat meal had no effect on the pharmacokinetics of the drug. Sitagliptin is metabolized to a limited extent by CYP isoenzymes 3A4 and 2C8 to active metabolites. Terminal half-life of sitagliptin is 12.4 hours following oral administration of a 100 mg oral dose. Following administration of a single radiolabeled dose, 87% of the dose was excreted in the urine (mainly as unchanged drug) and 13% was excreted in the feces.