Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Januvia: 25 mg, 50 mg, 100 mg
Pharmacology
Mechanism of Action
Sitagliptin inhibits dipeptidyl peptidase-4 (DPP-4) 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-4 enzyme.
Pharmacokinetics/Pharmacodynamics
Absorption
Rapid
Distribution
~198 L
Metabolism
Not extensively metabolized; minor metabolism via CYP3A4 and 2C8 to metabolites (inactive) suggested by in vitro studies
Excretion
Urine 87% (~79% as unchanged drug, 16% as metabolites); feces 13%
Time to Peak
1 to 4 hours
Half-Life Elimination
12.4 hours
Protein Binding
38%
Use in Specific Populations
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: 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, as monotherapy or combination therapy.
Contraindications
Serious hypersensitivity (eg, anaphylaxis, angioedema) to sitagliptin or any component of the formulation
Dosage and Administration
Dosing: Adult
Note: Due to lack of additive glycemic benefit, use in combination with a glucagon-like peptide-1 (GLP-1) receptor agonist (eg, exenatide) should be avoided (Dungan 2019; Nauck 2017).
Diabetes mellitus, type 2, treatment:
Note: May be used as an adjunctive agent or alternative monotherapy for patients who fail initial therapy with lifestyle intervention and metformin or who cannot take metformin. Use of sitagliptin is usually limited to patients close to their glycemic goal and without cardiovascular disease, especially when there is a need to minimize the risk of hypoglycemia (ADA 2019; Dungan 2019).
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.
Administration
Oral: Administer without regard to meals.
Dietary Considerations
Individualized medical nutrition therapy (MNT) based on American Diabetes Association (ADA) recommendations is an integral part of therapy.
Storage
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).
Drug Interactions
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
Angiotensin-Converting Enzyme Inhibitors: Dipeptidyl Peptidase-IV Inhibitors may enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. Monitor therapy
Digoxin: SITagliptin may increase the serum concentration of Digoxin. Monitor therapy
Direct Acting Antiviral Agents (HCV): May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy
Erdafitinib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy
Guanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. 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
Insulins: Dipeptidyl Peptidase-IV Inhibitors may enhance the hypoglycemic effect of Insulins. Management: Consider a decrease in insulin dose when initiating therapy with a dipeptidyl peptidase-IV inhibitor and monitor patients for hypoglycemia. Consider therapy modification
Lasmiditan: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Avoid combination
Lumacaftor and Ivacaftor: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. Lumacaftor and Ivacaftor may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy
Maitake: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy
Monoamine Oxidase 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
Prothionamide: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy
Quinolones: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolones 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
Ritodrine: May diminish the therapeutic effect of Antidiabetic Agents. 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: Dipeptidyl Peptidase-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
Adverse Reactions
1% to 10%:
Endocrine & metabolic: Hypoglycemia (1%)
Respiratory: Nasopharyngitis (5%)
Frequency not defined:
Gastrointestinal: Diarrhea, nausea
Renal: Increased serum creatinine
<1%, postmarketing, and/or case reports: Acute pancreatitis (including hemorrhagic or necrotizing forms), acute renal failure (possibly requiring dialysis), anaphylaxis, angioedema, arthralgia, back pain, bullous pemphigoid, constipation, exfoliative dermatitis, headache, hypersensitivity angiitis, hypersensitivity reaction, increased liver enzymes, limb pain, myalgia, oral mucosa ulcer, pain, pemphigoid, pruritus, renal insufficiency, rhabdomyolysis, severe arthralgia, skin rash (including macular), Stevens-Johnson syndrome, stomatitis, urticaria, vomiting
Warnings/Precautions
Concerns related to adverse effects:
- Arthralgia: Severe and disabling arthralgia has been reported with dipeptidyl peptidase-4 (DPP-4) 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-4 inhibitor therapy resumed.
- Bullous pemphigoid: DPP-4 inhibitor use has been associated with development of bullous pemphigoid; cases have typically resolved with topical or systemic immunosuppressive therapy and discontinuation of DPP-4 inhibitor therapy. Advise patients to report development of blisters or erosions. Discontinue therapy if bullous pemphigoid is suspected and consider referral to a dermatologist.
- 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 DPP-4 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.
- Renal effects: Worsening renal function, including acute renal failure, sometimes requiring dialysis has been reported.
Disease-related concerns:
- Bariatric surgery:
– Altered absorption: Absorption may be altered given the anatomic and transit changes created by gastric bypass and sleeve gastrectomy surgery (Mechanick 2013; Melissas 2013).
– Glucagon-like peptide-1 exposure and therapeutic efficacy: Closely monitor for signs and symptoms of pancreatitis; gastric bypass and sleeve gastrectomy may increase endogenous secretion of glucagon-like peptide-1 (Korner 2009; Peterli 2012). A single-dose, placebo-controlled study evaluated short-term therapy (4 weeks) with sitagliptin in gastric bypass patients having persistent or recurrent type 2 diabetes and found it to be well tolerated and provided a small but significant reduction in postprandial blood glucose (Shah 2018).
- Cardiovascular disease: In cardiovascular outcome trials of patients with type 2 diabetes and atherosclerotic cardiovascular disease, treatment with other DPP-4 inhibitors has been associated with HF. 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]). However, 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) with sitagliptin 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; McGuire 2016). The ADA suggests DPP-4 inhibitors (except saxagliptin) may be considered in patients with HF (ADA 2019).
- Renal impairment: 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.
Other warnings/precautions:
- Appropriate use: Not indicated for use in patients with type 1 diabetes or in patients with diabetic ketoacidosis (DKA).
- Patient education: Diabetes self-management education is essential to maximize the effectiveness of therapy.
Monitoring Parameters
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 2019]), serum glucose; renal function prior to initiation and periodically during treatment; signs/symptoms of heart failure
Pregnancy
Pregnancy Considerations
Information related to the use of sitagliptin in pregnancy is limited (Sun 2017).
Poorly controlled diabetes during pregnancy can be associated with an increased risk of adverse maternal and fetal outcomes, including diabetic ketoacidosis, preeclampsia, spontaneous abortion, preterm delivery, delivery complications, major birth defects, stillbirth, and macrosomia. 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 (ADA 2020; Blumer 2013).
Agents other than sitagliptin are currently recommended to treat diabetes mellitus in pregnancy (ADA 2020).
Health care providers are encouraged to enroll women exposed to sitagliptin during pregnancy in the registry (1-800-986-8999).
Patient Education
What is this drug used for?
- It is used to lower blood sugar in patients with high blood sugar (diabetes).
Frequently reported side effects of this drug
- Headache
- Common cold symptoms
- Nose irritation
- Throat irritation
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Heart problems like cough or shortness of breath that is new or worse, swelling of the ankles or legs, abnormal heartbeat, weight gain of more than five pounds in 24 hours, dizziness, or passing out
- Kidney problems like not able to pass urine, blood in the urine, change in amount of urine passed, or weight gain
- Pancreatitis like severe abdominal pain, severe back pain, severe nausea, or vomiting
- Low blood sugar like dizziness, headache, fatigue, feeling weak, shaking, a fast heartbeat, confusion, hunger, or sweating.
- Skin blisters
- Skin breakdown
- Severe joint pain
- Persistent joint pain
- Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes.
- Signs of a significant reaction like 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. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
