Sitagliptin

Sitagliptin is an oral antidiabetic medication that belongs to the dipeptidyl peptidase-4 (DPP-4) inhibitors class. It is used to improve glycemic control in adults with type 2 diabetes and is approved for use as monotherapy or in combination with other antidiabetic agents, such as metformin, a sulfonylurea, pioglitazone, or insulin. It is not indicated for type 1 diabetes or for treatment of diabetic ketoacidosis. The drug is marketed alone as sitagliptin and in combination products such as sitagliptin/metformin.

Mechanism of action: Sitagliptin inhibits the DPP-4 enzyme, which increases levels of incretin hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). The resulting rise in incretins enhances glucose-dependent insulin secretion and suppresses postprandial glucagon release, contributing to lower blood glucose levels.

Pharmacokinetics and administration: Sitagliptin is taken orally and can be administered with or without food. It is largely excreted unchanged by the kidneys, and its half-life is approximately 12 hours. Dose adjustments are recommended for patients with reduced renal function.

Dosing by renal function (typical): with estimated glomerular filtration rate (eGFR) ≥ 50 mL/min/1.73 m2, 100 mg once daily; eGFR 30–50, 50 mg once daily; eGFR < 30, 25 mg once daily. In patients on dialysis, 25 mg once daily is used. No routine hepatic dose adjustment is required.

Adverse effects and precautions: Sitagliptin is generally well tolerated. Common adverse events include nasopharyngitis, upper respiratory tract infection, and headache. There have been rare reports of pancreatitis and hypersensitivity reactions, and some patients may experience arthralgia. Caution is advised when used with insulin or sulfonylureas due to an increased risk of hypoglycemia. Safety in pregnancy is not definitively established; use only if clearly needed.