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Sitagliptin Phosphate


Pronunciation: SYE-ta-GLIP-tin FOS-fate
Class: Antidiabetic agent

Trade Names

- Tablets, oral 25 mg
- Tablets, oral 50 mg
- Tablets, oral 100 mg


Sitagliptin is a dipeptidyl peptidase-4 inhibitor that is thought to act in type 2 diabetes by slowing the inactivation of incretin hormones.

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Sitagliptin is rapidly absorbed, with a 100 mg dose reaching a C max of 950 nM in 1 to 4 h; AUC was 8.52 mcM. The bioavailability is approximately 87%.


Vd is approximately 198 L. Plasma protein binding is 38%.


Metabolism by CYP3A4 and, to a lesser degree, CYP2C8.


Terminal half-life is approximately 12.4 h and renal Cl is approximately 350 mL/min. Approximately 13% is excreted in the feces and 87% in the urine via active tubular secretion (79% as unchanged drug). Sitagliptin is a substrate for organic anion transport.

Special Populations

Renal Function Impairment

Plasma AUC levels of sitagliptin were increased approximately 2- and 4-fold in patients with moderate and severe renal impairment, including patients with ESRD on hemodialysis, respectively. Dosage adjustment is required.

Hepatic Function Impairment

Mean AUC and C max of sitagliptin increased approximately 21% and 13%, respectively, in patients with moderate hepatic impairment. There is no clinical experience in patients with severe hepatic impairment.


Elderly patients had an approximate 19% higher plasma concentration; no dosage adjustment is required.


Studies characterizing the pharmacokinetics of sitagliptin in children have not been performed.


No clinically meaningful effects on the pharmacokinetics of sitagliptin were observed.

Indications and Usage

Adjunct to diet and exercise to improve glycemic control in adult patients with type 2 diabetes mellitus as monotherapy or as combination therapy.


History of a serious hypersensitivity reaction to sitagliptin.

Dosage and Administration


PO 100 mg once daily.

Renal Function Impairment
Adults Moderate renal impairment (CrCl 30 to less than 50 mL/min or approximate serum creatinine levels of more than 1.7 up to 3 mg/dL in men and more than 1.5 up to 2.5 mg/dL in women)

PO 50 mg once daily.

Severe renal impairment (CrCl less than 30 mL/min or approximate serum creatinine levels of more than 3 mg/dL in men and more than 2.5 mg/dL in women)

PO 25 mg once daily.

ESRD requiring hemodialysis or peritoneal dialysis

PO 25 mg once daily. Administer without regard to the timing of hemodialysis.

General Advice

  • Instruct patients to take with or without food.
  • Instruct patients to swallow the tablet whole and not to split, crush, or chew before swallowing.
  • When used in combination with an insulin secretagogue (eg, sulfonylurea) or with insulin, a lower dose of the insulin secretagogue or insulin may be required to reduce the risk of hypoglycemia.


Store at 59° to 86°F.

Drug Interactions


Sitagliptin plasma concentrations may be increased modestly (approximately 68%), which is not expected to be clinically important.


Digoxin plasma concentrations may be increased slightly (approximately 18%); no dosage adjustment is recommended.

Insulin, sulfonylureas (eg, tolbutamide)

A lower dose of the insulin or sulfonylurea may be needed to reduce the risk of hypoglycemia.

Adverse Reactions


Diarrhea (3%); abdominal pain (2%); nausea (1%); acute pancreatitis including fatal and nonfatal hemorrhagic and necrotizing pancreatitis, constipation, hepatic enzyme elevations, vomiting (postmarketing).


Increased serum creatinine; worsening renal function including acute renal failure sometimes requiring dialysis (postmarketing).


Hypersensitivity reactions, including anaphylaxis, angioedema, cutaneous vasculitis, exfoliative skin conditions (including Stevens-Johnson syndrome), rash, and urticaria (postmarketing).


Nasopharyngitis, upper respiratory tract infection (5%).


Headache (1%); hypoglycemia.



Periodically monitor blood glucose and HbA 1c . Assess renal function prior to initiation of therapy and periodically thereafter. Observe patients carefully for signs and symptoms of pancreatitis.


Category B .




Safety and efficacy not established.


Use with caution.


Use with caution in patients with a history of angioedema. Serious hypersensitivity reactions, including anaphylaxis, angioedema, and exfoliative skin conditions, including Stevens-Johnson syndrome, have occurred.

Renal Function

Use caution to ensure the correct dose of sitagliptin is prescribed for patients with moderate to severe renal impairment and in patients with ESRD requiring hemodialysis or peritoneal dialysis.


Acute pancreatitis, both fatal and nonfatal hemorrhagic or necrotizing pancreatitis, has been reported.

Type 1 diabetes/diabetic ketoacidosis

Do not use sitagliptin in these settings.



Mean increases in QTc interval of 8 msec, which were not considered clinically important, were observed at a dose of 800 mg. There is no experience with doses more than 800 mg.

Patient Information

  • Advise patients to read the Medication Guide before starting therapy and to read it again with each refill.
  • Inform patients of the potential risks and benefits of sitagliptin and of alternative modes of therapy. Also inform patients about the importance of adherence to dietary instructions, regular physical activity, periodic blood glucose monitoring and HbA 1c testing, recognition and management of hypoglycemia and hyperglycemia, and assessment for diabetes complications. During periods of stress, such as fever, trauma, infection, or surgery, medication requirements may change; advise patients to seek medical advice promptly.
  • Inform patients that acute pancreatitis has been reported during postmarketing use of sitagliptin. Inform patients that persistent, severe abdominal pain, sometimes radiating to the back, which may or may not be accompanied by vomiting, is the hallmark symptom of acute pancreatitis. Instruct patients to promptly discontinue sitagliptin and contact their health care provider if persistent abdominal pain occurs.
  • Inform patients that the incidence of hypoglycemia is increased when sitagliptin is added to a sulfonylurea or insulin, and that a lower dose of the sulfonylurea or insulin may be required to reduce the risk of hypoglycemia.
  • Inform patients that allergic reactions have been reported during postmarketing use of sitagliptin. If symptoms of allergic reactions, including rash, hives, and swelling of the face, lips, tongue, and throat that may cause difficulty in breathing or swallowing, occur, advise patients to stop taking sitagliptin and seek medical advice promptly.
  • Inform patients that the tablets must be swallowed whole and never split, crushed, or chewed.

Copyright © 2009 Wolters Kluwer Health.