Sitagliptin (Januvia) is an orally available medicine that belongs to the class of medicines called DPP-IV (dipeptidyl peptidase IV) inhibitors. It can be used in a once-daily or twice-daily dose. Other DPP-IV inhibitors include:

• Vildagliptin
• Linagliptin
• Saxagliptin

Vildagliptin has a shorter half-life compared to sitagliptin. Compared to vildagliptin, sitagliptin is less effective in lowering the A1C.

Sitagliptin Uses:

• Diabetes mellitus Type 2:

  • As an adjunct to diet and exercise to optimize glycemic control in adults with type 2 diabetes mellitus, in the form of monotherapy or combination therapy.

Sitagliptin dose in Adults

Note: The supplementary use of a glucagon-like peptide-1 (GLP-1) receptor agonist (such as exenatide, dulaglutide) should be avoided because there is no further glycemic benefit.

Sitagliptin dose in the treatment of Diabetes mellitus:

Note:

• For patients who did not respond well to early therapy with dietary changes and metformin use or who could not take metformin, this medication may be administered either in combination therapy or as an alternative to monotherapy.
• To reduce the risk of hypoglycemia, sitagliptin is often only used in patients who are near to their glycemic goal and are healthy cardiovascular patients.
• Sitagliptin is typically used once or twice daily in doses of 25 mg to 100 mg.

Sitagliptin dose in patients on concomitant insulin or insulin secretagogues:

• • Reduction in dose of insulin and/or insulin secretagogues may be needed.

Sitagliptin dose in Children

Not recommended in children

Pregnancy Risk Category: B

• Maternal hyperglycemia in women with diabetes can lead to congenital anomalies and adverse effects on the fetus, neonate and mother.
• Preventing undesirable outcomes is possible by keeping maternal blood glucose and HbA1C within a close range. This will allow you to achieve your goals, while avoiding significant hypoglycemia.
• Pregnant women with diabetes should be treated with agents other than sitagliptin.

Sitagliptin can be used during breastfeeding

• There is no data to indicate if sitagliptin may be present in breast milk.
• The company advises weighing the benefits to the mother and the hazards to the infant while deciding whether to breastfeed while receiving therapy.

Sitagliptin dose in patients with kidney disease:

• eGFR >=45mL/minute/1.73m 2

  • There is no need to adjust the dosage.

• eGFR >=30 - 45mL/minute/1.73m 2

  • 50mg once per day

• eGFR 30mL/minute/1.73m 2

  • 25mg once daily

• ESRD that requires hemodialysis, peritoneal dialysis, or both:

  • 25mg once daily; do not worry about the timing of hemodialysis

Sitagliptin dose in patients with liver disease:

• Mild to moderate impairment (Child Puugh classes A andB)

  • There is no need to adjust the dosage.

• Severe impairment (Child Puugh class C).

  • The manufacturer's labeling does not contain any dosage adjustments (hasn't been studied).

Common Side Effects of Sitagliptin (Januvia):

• Endocrine & metabolic:

  • Hypoglycemia

• Respiratory:

  • Nasopharyngitis

Uncommon Side effects of Sitagliptin:

• Gastrointestinal:

  • Diarrhea
  • Nausea

• Renal:

  • Increased serum creatinine

Contraindication to Sitagliptin (Januvia):

• Extreme sensitivity to sitagliptin or any other formulation ingredient (eg anaphylaxis, edema)

Warnings and precautions

• Arthralgia

  • Dipeptidyl Peptidase-4 (DPP-4) inhibitors can cause severe and disabling pains in the joints. These symptoms may appear within a few days to years of treatment. They may disappear with discontinuation.
  • If DPP-4 inhibitor therapy is reintroduced, symptoms may recur.

• Bullous pemphigoid

  • Bullous pemphigoid has been linked to DPP-4 inhibitor usage. This can be treated with either topical or systemic immunosuppressive treatment and then the DPP-4 inhibited is removed.
  • Patients should be advised to immediately report any blisters or erosions.
  • If bullous pemphigoid symptoms are suspected, discontinue treatment and consult a dermatologist.

• Hypersensitivity reactions

  • Serious hypersensitivity responses like anaphylaxis, edoema, and exfoliative skin reactions like Stevens Johnson syndrome have been reported.
  • If you experience hypersensitivity reactions, discontinue use.
  • Generally, events are noted within the first three months of therapy. They may also occur after the first dose.
  • If the patient has had angioedema from other DPP-4 inhibitors, be cautious.

• Pancreatitis

  • Use has been associated with cases of acute pancreatitis, including hemorhagic and necrotizing deaths.
  • You should be aware of signs and symptoms of pancreatitis.
  • If pancreatitis is suspected, stop using the medication immediately and seek appropriate treatment.
  • Patients with a history or pancreatitis should be cautious. It is not known if they are at higher risk.

• Effects on the renal system:

  • A decrease in renal function can lead to acute renal failure that may require dialysis.

• Bariatric surgery

  • Absorption altered:

    • Absorption may be impacted by the anatomical and transit changes brought on by gastric bypass and sleeve gastrectomy surgery.

  • Exposure to Glucagon-like peptide-1 and its therapeutic efficacy

    • Monitor your pancreatitis symptoms and signs carefully
    • Gastric bypass and Sleeve gastrectomy can increase endogenous production of glucagon-like Peptide-1.
    • The placebo-controlled, single-dose study examined short-term sitagliptin therapy for type 2 diabetes in patients undergoing gastric bypass. It was found to be well tolerated and resulted in a modest but significant decrease in blood glucose postprandially.

• Cardiovascular disease

  • Heart failure has been linked to treatment with DPP-4 inhibitors in cardiovascular outcome trials of type 2 diabetic patients and patients with atherosclerotic cardio disease.
  • According to the American Heart Association, sitagliptin could increase myocardial dysfunction.
  • Sitagliptin was not found to be superior to placebo in the occurrences of the primary composite cardiovascular outcome in a significant randomised, double-blinded study in patients with type 2 diabetes and established cardiovascular disease (history of major CAD, ischemic cerebral disease, or atherosclerotic peripheral arterial disease) (cardiovascular deaths, nonfatal MI, or hospitalisation in unstable angina).
  • Hospitalizations for heart failure did not differ between the groups in terms of frequency.
  • Except for saxagliptin, DPP-4 inhibitors may be suggested by the ADA for HF patients.

• Renal impairment

  • Patients with severe or moderate renal impairment and end-stage renal disease (ESRD), which may require hemodialysis, peritoneal dialysis, or hemodialysis should be cautious.
  • In renal impairment, sitagliptin dosage adjustment is necessary.

Sitagliptin: Drug Interaction

Notice: Drug Interaction Categories

• Risk Factor CUse Combination Carefully
• Risk Factor DTake into consideration treatment modification
• Risk Factor XAvoid concurrent use

Monitoring parameters:

• Patients who are stable in glycemic control, and have achieved their treatment goals, should undergo HbA at least twice a year.
• Patients who fail to achieve their treatment goals or have therapy changed, should check the glycated hemoglobin at three months interval (4 times per year)
• Monitor for the signs and symptoms of heart failure

How to administer Sitagliptin?

Oral: Administer without regard to meals. However, when taken with meals, the gastrointestinal side effects are minimized.

Mechanism of action of Sitagliptin (Januvia):

• Sitagliptin blocks the dipeptidylpeptidase-4 enzyme (DPP-4), resulting in higher levels of active incretin for a longer period.
• Incretin hormones, such as glucagon-like protein-1 [GLP-1] or glucose-dependent insulinotropic peptide [GIP], regulate glucose homeostasis.
• They increase insulin synthesis and release by pancreatic beta cells while decreasing pancreatic alpha cell glucagon production.
• Hepatic glucose synthesis decreases when glucagon output is reduced.
  The intestine releases incretin hormones continuously throughout the day under normal physiological conditions. Levels may rise as a result of dietary consumption.
• DPP-4 enzyme is responsible for rapid activation of incretin hormones.

Absorption:

• Rapid

Distribution:

• ~198 L

Protein binding:

• 38%

Metabolism:

• Not substantially metabolised; in vitro studies reveal a limited amount of metabolism via CYP3A4 and 2C8 to metabolites (inactive).

Bioavailability:

• ~87%

Half-life elimination:

• 12.4 hours

Time to peak, plasma:

• 1 to 4 hours

Excretion:

• Urine 87% (~79% excreted as unchanged drug, 16% excreted as metabolites);
• feces 13%

International Brands of Sitagliptin:

• Januvia
• Fazique
• Glactiv
• Glipita
• Inosita
• Janaglip
• Januvia XR
• Janvia
• Ristaben
• Sitagen
• Sitalia
• Sitap
• Sitrg
• Sliptin
• Tesavel
• Xelevia

Sitagliptin Brand Names in Pakistan: