Usage
- Sitagliptin is prescribed as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. It is not indicated for type 1 diabetes or diabetic ketoacidosis.
- Pharmacological Classification: Dipeptidyl peptidase-4 (DPP-4) inhibitor, Antidiabetic agent.
- Mechanism of Action: Sitagliptin works by inhibiting the DPP-4 enzyme. This enzyme normally breaks down incretin hormones like GLP-1 and GIP, which stimulate insulin release and suppress glucagon secretion in response to food intake. By inhibiting DPP-4, sitagliptin increases the levels of these incretins, leading to better blood glucose control after meals.
Alternate Names
- International Nonproprietary Name (INN): Sitagliptin
- Brand Names: Januvia®, Xelevia®, Tesavel®, Sitagliptin Phosphate, Sitagliptin Sandoz Pharma®, Sitapril®
How It Works
- Pharmacodynamics: Sitagliptin increases incretin levels (GLP-1 and GIP), resulting in glucose-dependent insulin secretion, decreased glucagon secretion, and improved postprandial glycemic control.
- Pharmacokinetics:
- Absorption: Sitagliptin is rapidly absorbed after oral administration, with peak plasma concentrations occurring 1 to 4 hours post-dose.
- Metabolism: Minimally metabolized, primarily by CYP3A4, with a major metabolite having negligible DPP-4 inhibitory activity.
- Elimination: Primarily renal excretion (approximately 87%), with a small amount (13%) eliminated in the feces. The terminal half-life is about 12.4 hours.
- Mode of Action: Sitagliptin selectively and reversibly inhibits DPP-4, preventing the breakdown of incretin hormones. This results in increased incretin concentrations, leading to improved glucose-dependent insulin secretion and reduced glucagon levels.
- Receptor Binding/Enzyme Inhibition: Sitagliptin acts through competitive, reversible inhibition of the DPP-4 enzyme.
- Elimination Pathways: Primarily renal excretion (both as unchanged drug and metabolites), with a minor contribution from hepatic metabolism via CYP3A4.
Dosage
Standard Dosage
Adults:
- 100 mg orally once daily, with or without food.
Children:
- Not recommended for use in patients under 18 years of age due to insufficient efficacy data.
Special Cases:
- Elderly Patients: No dose adjustment is necessary based on age alone. However, renal function should be assessed.
- Patients with Renal Impairment:
- eGFR ≥ 45 mL/min/1.73 m²: No dosage adjustment required.
- eGFR 30 to < 45 mL/min/1.73 m²: 50 mg once daily.
- eGFR < 30 mL/min/1.73 m² (including ESRD requiring dialysis): 25 mg once daily.
- Patients with Hepatic Dysfunction: No dose adjustment is necessary for mild to moderate hepatic impairment. Use with caution in severe hepatic impairment.
- Patients with Comorbid Conditions: Assess renal function and adjust dosage accordingly. Use with caution in patients with a history of pancreatitis or heart failure.
Clinical Use Cases
Sitagliptin is specifically indicated for type 2 diabetes as an adjunct to diet and exercise. It does not have clinical use cases for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
Dose adjustments are primarily necessary for patients with renal impairment based on eGFR, as outlined above. Concomitant use of strong CYP3A4 inhibitors may necessitate dosage reduction.
Side Effects
Common Side Effects
- Upper respiratory tract infection
- Runny nose, stuffy nose, sore throat
- Headache
Rare but Serious Side Effects
- Pancreatitis (including fatal and non-fatal hemorrhagic or necrotizing pancreatitis)
- Angioedema and anaphylaxis
- Severe and disabling arthralgia
- Bullous pemphigoid
- Acute renal failure
- Heart failure
- Stevens-Johnson syndrome
- Cutaneous vasculitis
Long-Term Effects
The potential long-term effects of sitagliptin are still being investigated, but post-marketing surveillance has identified rare cases of pancreatitis and renal function deterioration.
Adverse Drug Reactions (ADR)
ADRs requiring immediate intervention include symptoms of pancreatitis (severe abdominal pain, nausea, vomiting), hypersensitivity reactions (angioedema, anaphylaxis), and signs of acute renal failure.
Contraindications
- History of serious hypersensitivity reaction to sitagliptin (e.g., anaphylaxis, angioedema).
Drug Interactions
- CYP3A4 Inhibitors (e.g., ketoconazole, itraconazole): May increase sitagliptin exposure and require dosage adjustment.
- CYP3A4 Inducers (e.g., rifampin): May decrease sitagliptin exposure.
- Digoxin: May increase digoxin levels; monitor digoxin levels.
- Insulin Secretagogues/Insulin: Increased risk of hypoglycemia.
- Alcohol: Potential increased risk of pancreatitis.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Category B. Sitagliptin should not be used during pregnancy unless the benefits outweigh the risks.
- Breastfeeding: Sitagliptin is excreted in rat milk. It is unknown if sitagliptin is excreted in human milk. Sitagliptin should not be used while breastfeeding.
Drug Profile Summary
- Mechanism of Action: DPP-4 inhibitor, increasing incretin levels.
- Side Effects: Upper respiratory infection, nasopharyngitis, headache, pancreatitis (rare), hypersensitivity reactions (rare).
- Contraindications: Hypersensitivity to sitagliptin.
- Drug Interactions: CYP3A4 inhibitors, digoxin, insulin secretagogues.
- Pregnancy & Breastfeeding: Not recommended.
- Dosage: 100 mg once daily (adjust for renal impairment).
- Monitoring Parameters: HbA1c, renal function, signs of pancreatitis/hypersensitivity.
Popular Combinations
- Metformin
- Sulfonylureas
- Pioglitazone
Precautions
- General Precautions: Assess renal function prior to and during treatment. Monitor for signs and symptoms of pancreatitis, hypersensitivity reactions, and heart failure.
- Specific Populations: See Dosage - Special Cases section.
- Lifestyle Considerations: Encourage a healthy diet and regular exercise.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Sitagliptin?
A: The standard recommended dosage is 100 mg orally once daily. Dosage adjustments are needed for patients with renal impairment.
Q2: How does sitagliptin differ from other antidiabetic medications?
A: Sitagliptin, a DPP-4 inhibitor, works by increasing incretin levels, thereby enhancing glucose-dependent insulin release. Other classes, such as sulfonylureas, directly stimulate insulin release, while metformin primarily reduces hepatic glucose production.
Q3: What are the most serious side effects of sitagliptin?
A: Pancreatitis (rare but potentially fatal), severe hypersensitivity reactions (angioedema, anaphylaxis), and acute renal failure are the most serious side effects.
Q4: Can sitagliptin be used in patients with type 1 diabetes?
A: No, sitagliptin is not indicated for patients with type 1 diabetes. It is specifically for type 2 diabetes mellitus.
Q5: What are the key drug interactions to be aware of with sitagliptin?
A: Concomitant use of CYP3A4 inhibitors may increase sitagliptin exposure and require dosage adjustments. Also, combined use with insulin or insulin secretagogues increases the risk of hypoglycemia.
Q6: What are the monitoring parameters for patients on sitagliptin?
A: HbA1c should be regularly monitored to assess glycemic control. Renal function should be assessed before initiating therapy and periodically thereafter. Patients should be monitored for signs and symptoms of pancreatitis and hypersensitivity reactions.
Q7: Can sitagliptin be used during pregnancy or breastfeeding?
A: Sitagliptin is generally not recommended for use during pregnancy or breastfeeding. Consult a specialist for risk/benefit assessment if considering its use in these situations.
Q8: Can Sitagliptin be crushed or chewed?
A: Sitagliptin tablets should be swallowed whole and not crushed or chewed.
Q9: What should a patient do if they miss a dose of sitagliptin?
A: Patients should take the missed dose as soon as they remember. However, if it is close to the time for the next dose, they should skip the missed dose and take the next dose at the regular time. They should not double the dose to catch up.
