Overview
Sitagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor used as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. It works by increasing incretin levels, which stimulate insulin release and reduce glucagon secretion in a glucose-dependent manner. It is not recommended for type 1 diabetes or diabetic ketoacidosis.
Mechanism of Action
Sitagliptin is a selective, competitive dipeptidyl peptidase-4 (DPP-4) inhibitor that slows the inactivation of incretin hormones GLP-1 and GIP. This increases active incretin levels, stimulating glucose-dependent insulin secretion from pancreatic beta cells and decreasing glucagon secretion from pancreatic alpha cells, resulting in reduced hepatic glucose production.
Indications
- Adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus
Common Doses
- 25 mg
- 50 mg
- 100 mg
Dosage
For monotherapy: 100 mg once daily. For combination therapy with metformin: 100 mg once daily. For combination therapy with sulfonylurea or insulin: may require lower doses of the insulin secretagogue or insulin. Dose adjustment required for renal impairment.
Contraindications
- Severe renal impairment (eGFR below 30 mL/min/1.73 m²)
- Acute or chronic metabolic acidosis, including diabetic ketoacidosis
- History of serious hypersensitivity reaction to sitagliptin or any excipients
Side Effects
- Upper respiratory tract infection
- Nasopharyngitis
- Headache
- Hypoglycemia (when used with insulin or sulfonylureas)
- Pancreatitis
- Acute renal failure
- Severe arthralgia
- Bullous pemphigoid
- Hypersensitivity reactions
Interactions
- Carbonic anhydrase inhibitors (increased risk of lactic acidosis)
- Drugs that reduce metformin clearance (e.g., ranolazine, vandetanib, dolutegravir, cimetidine)
- Alcohol (potentiates metformin's effect on lactate metabolism)
- Insulin secretagogues or insulin (increased hypoglycemia risk)
- Drugs affecting glycemic control (thiazides, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blockers, isoniazid)
Counseling Points
- Take once daily with or without food
- Do not use for type 1 diabetes or diabetic ketoacidosis
- Report symptoms of pancreatitis (severe abdominal pain, nausea, vomiting)
- Monitor for signs of heart failure (shortness of breath, edema, rapid weight gain)
- Report severe joint pain or skin blistering
- Carry glucose source if taking with insulin or sulfonylureas
- Avoid excessive alcohol consumption