saxagliptin

Saxagliptin is an oral antidiabetic medication that acts as a dipeptidyl peptidase-4 (DPP-4) inhibitor. It is marketed as Onglyza and is approved for adults with type 2 diabetes to improve glycemic control in addition to diet and exercise; it can be used as monotherapy or in combination with other antidiabetic agents such as metformin, SU, thiazolidinediones, or insulin.

The drug works by inhibiting DPP-4, which raises levels of incretin hormones such as GLP-1 and GIP. The increase in incretins enhances glucose-dependent insulin secretion from pancreatic beta cells and suppresses glucagon release from alpha cells, contributing to lower blood glucose. Incretin effects may also slow gastric emptying.

Administration and dosing are once daily by mouth, with or without food. The usual dose is 5 mg daily. In patients with moderate to severe renal impairment (creatinine clearance below 50 mL/min), the dose is reduced to 2.5 mg daily. Saxagliptin is not indicated for type 1 diabetes or diabetic ketoacidosis, and safety in pregnancy has not been established.

Pharmacokinetically, saxagliptin is metabolized to an active metabolite and eliminated through both renal and hepatic pathways. Dose adjustments are recommended in renal impairment, and potential drug interactions should be considered. Potent CYP3A4 inhibitors (for example ketoconazole) increase exposure to saxagliptin, necessitating a dose reduction. Strong CYP3A4 inducers may reduce its effectiveness.

Common adverse effects include upper respiratory tract infection, urinary tract infection, and headache. Rare but serious risks include pancreatitis, hypersensitivity reactions, and an increased possibility of heart failure requiring hospitalization in patients with preexisting heart failure. Saxagliptin should be used with caution in patients with cardiovascular disease and discontinued if pancreatitis or severe hypersensitivity occurs.