Sitagliptin

Sitagliptin is an oral antidiabetic medication used to treat type 2 diabetes. Sitagliptin is an oral dipeptidyl peptidase-4 (DPP-4) inhibitor used in conjunction with diet and exercise to improve blood sugar control. It is taken by mouth. It is also available in the fixed-dose combination medication sitagliptin/metformin.

Pharmacodynamics

Inhibition of DPP-4 by sitagliptin slows DPP-4-mediated inactivation of incretins such as GLP-1 and GIP. Incretins are released throughout the day and upregulated in response to meals as part of glucose homeostasis. Decreased inhibition of incretins increases insulin synthesis and decreases glucagon release in a glucose concentration-dependent manner. These effects result in an overall improvement in glycemic control, as evidenced by reduced glycosylated hemoglobin (HbA1c).

Pharmacokinetics

Sitagliptin is 87% orally bioavailable and taking it with or without food does not affect its pharmacokinetics. Sitagliptin reaches maximum plasma concentration within 2 hours. Protein binding is approximately 38%. Sitagliptin is largely unmetabolized, with 79% of the dose excreted in the urine as the unchanged parent compound. Minor metabolic pathways are mediated primarily by cytochrome p450 CYP3A4 and to a lesser extent by CYP2C8. The plasma half-life is approximately 12.4 hours.

Side effects

Common side effects are headache, swelling of the legs, and upper respiratory tract infection. Serious side effects may include angioedema, low blood sugar, kidney problems, pancreatitis, and joint pain. It is unclear whether it is safe to use during pregnancy or breastfeeding.