Sitagliptin

Generic Name: Sitagliptin
Brand Names: Januvia, Tesavel, Xelevia, Ristaben, Glactiv
Formulation: Oral tablet (25 mg, 50 mg, 100 mg)
Available Presentation: Film-coated tablets in blister packs or bottles
Route of Administration: Oral

Indication: Sitagliptin is indicated for the management of type 2 diabetes mellitus in adults as monotherapy or as part of combination therapy. It is used to improve glycemic control when diet and exercise alone are insufficient. Sitagliptin can be combined with metformin, sulfonylureas, glitazones, or insulin, depending on the patient's clinical needs.

Pharmacological Class: Dipeptidyl Peptidase-4 (DPP-4) Inhibitor

Mechanism of Action: Sitagliptin selectively inhibits the DPP-4 enzyme responsible for degrading incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). This inhibition prolongs the activity of these hormones, leading to glucose-dependent stimulation of insulin secretion and suppression of glucagon release, thereby improving both fasting and postprandial glucose levels.

Absorption: Sitagliptin has high oral bioavailability (approximately 87%) and reaches peak plasma concentrations within 1–4 hours after dosing.
Distribution: It has a volume of distribution of approximately 198 liters, indicating extensive tissue distribution. Plasma protein binding is low (~38%).
Metabolism: Sitagliptin undergoes minimal hepatic metabolism. It is primarily metabolized by cytochrome P450 enzymes CYP3A4 and CYP2C8, with most of the parent drug circulating unchanged.
Elimination: Sitagliptin is mainly excreted unchanged via the kidneys through active tubular secretion. Approximately 79% of the dose is recovered in the urine, and about 13% is excreted in the feces. The elimination half-life is approximately 12.4 hours, supporting once-daily dosing.

Standard Dosage (Adults): The usual recommended dose is 100 mg once daily with or without food.

Renal Impairment Dose Adjustments:
– Mild impairment (eGFR ≥45 to <90 mL/min/1.73 m²): no dose adjustment
– Moderate impairment (eGFR ≥30 to <45 mL/min/1.73 m²): 50 mg once daily
– Severe impairment (eGFR <30 mL/min/1.73 m²) or end-stage renal disease on dialysis: 25 mg once daily

Contraindications: Known hypersensitivity to sitagliptin or any excipient, history of serious hypersensitivity reactions including anaphylaxis, angioedema, or exfoliative skin conditions related to sitagliptin. Not indicated for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis.

Cautions and Warnings: Pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been reported. Discontinue immediately if pancreatitis is suspected. Use caution in patients with a history of pancreatitis. Monitor renal function periodically, especially in elderly patients. Hypoglycemia risk increases when used with insulin or sulfonylureas. Bullous pemphigoid, arthralgia, and hypersensitivity reactions such as urticaria and angioedema may occur.

Use in Pregnancy and Lactation: There is limited data on sitagliptin use in pregnancy. It should be used during pregnancy only if clearly needed. It is unknown whether sitagliptin is excreted in human milk; therefore, caution is advised when administered to breastfeeding women.

Adverse Effects (Common): Nasopharyngitis, headache, upper respiratory tract infection
Less Common but Serious: Acute pancreatitis, hypersensitivity reactions, bullous pemphigoid, joint pain, hepatic enzyme elevations

Drug Interactions: Sitagliptin has a low potential for drug–drug interactions. Co-administration with drugs that undergo active renal tubular secretion may alter its pharmacokinetics. Use caution when co-administered with digoxin, as plasma concentrations of digoxin may increase slightly. No significant interactions with metformin, sulfonylureas, pioglitazone, or simvastatin have been reported.

Monitoring Parameters: Blood glucose and HbA1c for glycemic control, renal function (eGFR) prior to initiation and periodically thereafter, signs and symptoms of pancreatitis, allergic reactions, and skin disorders.

Storage Conditions: Store at room temperature, away from moisture and heat. Protect from light and keep in original packaging until use. Keep out of reach of children