(sit a GLIP tin)
- Sitagliptin Phosphate
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Januvia: 25 mg, 50 mg, 100 mg
Brand Names: U.S.
- Antidiabetic Agent, Dipeptidyl Peptidase 4 (DPP-4) Inhibitor
Sitagliptin inhibits dipeptidyl peptidase IV (DPP-IV) enzyme resulting in prolonged active incretin levels. Incretin hormones (eg, glucagon-like peptide-1 [GLP-1] and glucose-dependent insulinotropic polypeptide [GIP]) regulate glucose homeostasis by increasing insulin synthesis and release from pancreatic beta cells and decreasing glucagon secretion from pancreatic alpha cells. Decreased glucagon secretion results in decreased hepatic glucose production. Under normal physiologic circumstances, incretin hormones are released by the intestine throughout the day and levels are increased in response to a meal; incretin hormones are rapidly inactivated by the DPP-IV enzyme.
Not extensively metabolized; minor metabolism via CYP3A4 and 2C8 to metabolites (inactive) suggested by in vitro studies
Urine 87% (~79% as unchanged drug, 16% as metabolites); feces 13%
Time to Peak
1 to 4 hours
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.
Special Populations: Hepatic Function Impairment
Mean AUC and Cmax of sitagliptin increased approximately 21% and 13%, respectively, in patients with moderate hepatic impairment (Child-Pugh class B).
Special Populations: Elderly
Elderly patients had ~19% higher plasma concentration.
Use: Labeled Indications
Diabetes mellitus, type 2: As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (noninsulin dependent) as monotherapy or combination therapy.
Serious hypersensitivity (eg, anaphylaxis, angioedema) to sitagliptin or any component of the formulation
Diabetes mellitus, type 2: Oral: 100 mg once daily
Concomitant use with insulin and/or insulin secretagogues (eg, sulfonylureas): Reduced dose of insulin and/or insulin secretagogues may be needed.
Dosing: Renal Impairment
CrCl ≥50 mL/minute: No dosage adjustment necessary.
CrCl ≥30 to <50 mL/minute (approximate SCr of >1.7 to ≤3 mg/dL [males] or >1.5 to ≤2.5 mg/dL [females]): 50 mg once daily
CrCl <30 mL/minute (approximate SCr of >3 mg/dL [males] or >2.5 mg/dL [females]): 25 mg once daily
ESRD requiring hemodialysis or peritoneal dialysis: 25 mg once daily; administer without regard to timing of hemodialysis
Dosing: Hepatic Impairment
Mild to moderate impairment (Child-Pugh classes A and B): No dosage adjustment necessary.
Severe impairment (Child-Pugh class C):
US labeling: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Canadian labeling: Use is not recommended.
Administer without regard to meals.
Individualized medical nutrition therapy (MNT) based on American Diabetes Association (ADA) recommendations is an integral part of therapy.
Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
ACE Inhibitors: DPP-IV Inhibitors may enhance the adverse/toxic effect of ACE Inhibitors. Specifically, the risk of angioedema may be increased. Monitor therapy
Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy
Androgens: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Exceptions: Danazol. Monitor therapy
Digoxin: SITagliptin may increase the serum concentration of Digoxin. Monitor therapy
Hyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy
Hypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy
Insulin: DPP-IV Inhibitors may enhance the hypoglycemic effect of Insulin. Management: Consider a decrease in insulin dose when initiating therapy with a dipeptidyl peptidase-IV inhibitor and monitor patients for hypoglycemia. Consider therapy modification
Lumacaftor: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. Lumacaftor may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy
MAO Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy
Pegvisomant: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy
P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy
P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy
Quinolone Antibiotics: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolone Antibiotics may diminish the therapeutic effect of Blood Glucose Lowering Agents. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Monitor therapy
Ranolazine: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy
Salicylates: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy
Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy
Sulfonylureas: DPP-IV Inhibitors may enhance the hypoglycemic effect of Sulfonylureas. Management: Consider a decrease in sulfonylurea dose when initiating therapy with a dipeptidyl peptidase-IV inhibitor and monitor patients for hypoglycemia. Consider therapy modification
Thiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy
Reported with monotherapy.
1% to 10%:
Cardiovascular: Peripheral edema (2%)
Endocrine & metabolic: Hypoglycemia (1%)
Gastrointestinal: Diarrhea (4%), constipation (3%), nausea (2%)
Neuromuscular & skeletal: Osteoarthritis (1%)
Respiratory: Nasopharyngitis (5%), pharyngitis (1%), upper respiratory tract infection (viral; 1%)
<1% (important or life-threatening): Acne rosacea, acute pancreatitis (including hemorrhagic or necrotizing forms with some fatalities), acute renal failure (possibly requiring dialysis), anaphylaxis, anemia, bundle branch block, depression, erectile dysfunction, exfoliative dermatitis, gastritis (Helicobacter), gastroesophageal reflux disease, hypertension, hypersensitivity, hypersensitivity vasculitis, hypotension, increased liver enzymes, liver steatosis, migraine, orthostatic hypotension, pemphigoid, peripheral neuropathy, renal insufficiency, severe arthralgia (FDA Safety Alert, Aug 28, 2015), Stevens-Johnson syndrome
Concerns related to adverse effects:
• Arthralgia: Severe and disabling arthralgia has been reported with DPP-IV inhibitor use; onset may occur within one day to years after treatment initiation and may resolve with discontinuation of therapy. Some patients may experience a recurrence of symptoms if DPP-IV inhibitor therapy resumed.
• Hypersensitivity reactions: Serious hypersensitivity reactions, including anaphylaxis, angioedema, and exfoliative skin reactions, such as Stevens-Johnson syndrome, have been reported; discontinue if signs/symptoms of hypersensitivity reactions occur. Events have generally been noted within the first 3 months of therapy, and may occur with the initial dose. Use with caution if patient has experienced angioedema with other dipeptidyl peptidase IV (DPP-IV) inhibitor use.
• Pancreatitis: Cases of acute pancreatitis (including hemorrhagic and necrotizing with some fatalities) have been reported with use. Monitor for signs/symptoms of pancreatitis; discontinue use immediately if pancreatitis is suspected and initiate appropriate management. Use with caution in patients with a history of pancreatitis as it is not known if this population is at greater risk.
• Cardiovascular disease: No specific recommendations regarding patients with cardiovascular disease (including heart failure) are provided in the US labeling (Canadian labeling recommends against use in the heart failure population). Clinical trials included only a limited number of patients with heart failure. In one large randomized, double-blinded trial in patients with type 2 diabetes and established cardiovascular disease (history of major CAD, ischemic cerebrovascular disease, or atherosclerotic peripheral arterial disease), the occurrence of the primary composite cardiovascular outcome (cardiovascular death, nonfatal MI, nonfatal stroke, or hospitalization for unstable angina) was found to be noninferior to placebo. In addition, the rate of hospitalization for heart failure did not differ between the two groups (Green 2015). In a scientific statement from the American Heart Association, sitagliptin has been determined to be an agent that may exacerbate underlying myocardial dysfunction (magnitude: major) (AHA [Page 2016]).
• Diabetic ketoacidosis: Not indicated for the treatment of diabetic ketoacidosis due to lack of efficacy in this patient population.
• Diabetes mellitus, type 1: Not indicated for use in patients with type 1 diabetes mellitus (insulin dependent) due to lack of efficacy in this patient population.
• Hepatic impairment: Canadian labeling recommends against use in patients with severe hepatic impairment.
• Renal impairment: Worsening renal function, including acute renal failure, sometimes requiring dialysis has been reported. Use with caution in patients with moderate to severe renal dysfunction and end-stage renal disease (ESRD) requiring hemodialysis or peritoneal dialysis; dosing adjustment required.
Concurrent drug therapy issues:
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
• Patient education: Diabetes self-management education is essential to maximize the effectiveness of therapy.
HbA1c (at least twice yearly in patients who have stable glycemic control and are meeting treatment goals; quarterly in patients not meeting treatment goals or with therapy change [ADA 2016a]), serum glucose; renal function prior to initiation and periodically during treatment
Pregnancy Risk Factor
Adverse events have not been observed in animal reproduction studies.
In women with diabetes, maternal hyperglycemia can be associated with congenital malformations as well as adverse effects in the fetus, neonate, and the mother (ACOG 2005; ADA 2015; Kitzmiller 2008; Metzger 2007). To prevent adverse outcomes, prior to conception and throughout pregnancy maternal blood glucose and HbA1c should be kept as close to target goals as possible but without causing significant hypoglycemia (ACOG 2013; ADA 2015; Blumer 2013; Kitzmiller 2008). Prior to pregnancy, effective contraception should be used until glycemic control is achieved (Kitzmiller 2008). Other agents are currently recommended to treat diabetes in pregnant women (ACOG 2013; Blumer 2013).
Health care providers are encouraged to enroll women exposed to sitagliptin during pregnancy in the registry (1-800-986-8999).
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience headache, pharyngitis, rhinitis, rhinorrhea, or diarrhea. Have patient report immediately to prescriber signs of pancreatitis (severe abdominal pain, severe back pain, severe nausea, or vomiting), signs of low blood sugar (dizziness, headache, fatigue, feeling weak, shaking, a fast heartbeat, confusion, hunger, or sweating), urinary retention, change in amount of urine passed, severe joint pain, or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
More about sitagliptin
- Other brands: Januvia