Maglitin Mechanism of Action

Pharmacology: Pharmacodynamics: MAGLITIN (Sitagliptin phosphate) is an orally-active, potent, and highly selective inhibitor of the dipeptidyl peptidase 4 (DPP-4) enzyme for the treatment of type 2 diabetes. The DPP-4 inhibitors are a class of agents that act as incretin enhancers. By inhibiting the DPP-4 enzyme, sitagliptin increases the levels of two known active incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). The incretins are part of an endogenous system involved in the physiologic regulation of glucose homeostasis. When blood glucose concentrations are normal or elevated, GLP-1 and GIP increase insulin synthesis and release from pancreatic beta cells, GLP-1 also lowers glucagon secretion from pancreatic alpha cells, leading to reduced hepatic glucose production.
Pharmacokinetics: Absorption: The absolute bioavailability of sitagliptin is approximately 87%, since co-administration of a high-fat meal with MAGLITIN had no effect on the pharmacokinetics.
Distribution: The mean volume of distribution at steady state is approximately 198 liters. The fraction of sitagliptin reversibly bound to plasma proteins is low (38%).
Metabolism: Sitagliptin is primarily eliminated unchanged in urine, and metabolism is a minor pathway. Approximately 79% of sitagliptin is excreted unchanged in the urine. The primary enzyme responsible for the limited metabolism of sitagliptin was CYP3A4, with contribution from CYP2C8.
Elimination: Elimination of sitagliptin occurs primarily via renal excretion. Excretion is mainly via urine 87% (79% as unchanged drug, 16% as metabolite); feces 13%.