Usage
Gliclazide + Sitagliptin is prescribed for the treatment of type 2 diabetes mellitus in adults, specifically when diet and exercise alone, or in combination with metformin, do not provide adequate glycemic control. This combination therapy is not indicated for type 1 diabetes or diabetic ketoacidosis.
It falls under the pharmacological classification of antidiabetic agents, specifically combining a sulfonylurea (gliclazide) and a dipeptidyl peptidase-4 (DPP-4) inhibitor (sitagliptin).
Gliclazide works by stimulating insulin release from the pancreas. Sitagliptin works by increasing incretin levels, which in turn increase insulin release and decrease glucagon secretion. This combined approach helps to lower blood sugar levels.
Alternate Names
There is no single international nonproprietary name (INN) for the combination of gliclazide and sitagliptin. It is often referred to by the names of its individual components.
Brand names may vary depending on the region of use.
How It Works
Pharmacodynamics: Gliclazide acts on ATP-sensitive potassium channels in pancreatic beta cells, stimulating insulin release. Sitagliptin inhibits the DPP-4 enzyme, increasing the levels of incretin hormones like GLP-1 and GIP. These hormones enhance glucose-dependent insulin secretion and suppress glucagon secretion.
Pharmacokinetics:
- Gliclazide: Almost completely absorbed after oral administration. Metabolized primarily in the liver and excreted mainly through the kidneys.
- Sitagliptin: Well absorbed after oral administration. Primarily excreted unchanged in the urine with a small fraction metabolized by CYP3A4, predominantly to its inactive metabolite.
Mode of Action: Gliclazide binds to sulfonylurea receptors on pancreatic beta cells, closing ATP-sensitive potassium channels. This depolarizes the cell membrane, leading to calcium influx and subsequent insulin release. Sitagliptin inhibits DPP-4, preventing the breakdown of incretins. This increases incretin levels, leading to enhanced glucose-dependent insulin release and suppressed glucagon secretion.
Elimination Pathways: Gliclazide is metabolized by the liver and eliminated by the kidney. Sitagliptin is mainly excreted unchanged in urine.
Dosage
Standard Dosage
Children: The use of gliclazide + sitagliptin is not recommended in children. Safety and efficacy have not been established.
Special Cases:
- Elderly Patients: Dose adjustments may be necessary due to age-related decline in renal function. Start with a low dose and titrate carefully.
- Patients with Renal Impairment: Dose reduction of sitagliptin is recommended. Gliclazide use needs to be carefully considered.
- Patients with Hepatic Dysfunction: Dose adjustments may be required for gliclazide.
- Patients with Comorbid Conditions: Dosage should be individualized.
Dosage Adjustments: Dose adjustments may be necessary based on renal function, hepatic function, and concomitant medications.
Side Effects
Common Side Effects: Hypoglycemia, headache, nausea, diarrhea, upper respiratory tract infection.
Rare but Serious Side Effects: Pancreatitis, severe allergic reactions (including angioedema, Stevens-Johnson syndrome), bullous pemphigoid, acute renal failure.
Long-Term Effects: Potential long-term effects include chronic complications of diabetes if blood sugar is not adequately controlled.
Adverse Drug Reactions (ADR): The serious side effects mentioned above would qualify as clinically significant ADRs.
Contraindications
- Hypersensitivity to gliclazide, sitagliptin, or any component of the formulation.
- Type 1 diabetes mellitus.
- Diabetic ketoacidosis.
- Severe renal impairment.
- History of pancreatitis (especially with DPP-4 inhibitors).
- Severe hepatic impairment (gliclazide).
Drug Interactions
Gliclazide and sitagliptin can interact with various medications. Some notable interactions include:
- CYP3A4 Inhibitors/Inducers: May affect sitagliptin metabolism.
- Sulfonylureas/Insulin: Increased risk of hypoglycemia when combined.
- Other Antidiabetic Agents: Close monitoring required due to potential additive hypoglycemic effects.
- Alcohol: Increased risk of hypoglycemia.
Pregnancy and Breastfeeding
Gliclazide is contraindicated during pregnancy. Sitagliptin has limited human data, but animal studies suggest a low risk. Due to potential risks, alternative therapies are generally preferred during pregnancy and breastfeeding.
Drug Profile Summary
- Mechanism of Action: Gliclazide: Stimulates insulin release. Sitagliptin: Increases incretin levels.
- Side Effects: Hypoglycemia, headache, nausea, pancreatitis (rare), allergic reactions (rare).
- Contraindications: Type 1 diabetes, diabetic ketoacidosis, severe renal impairment, hypersensitivity.
- Drug Interactions: CYP3A4 inhibitors/inducers, other antidiabetic agents, alcohol.
- Pregnancy & Breastfeeding: Contraindicated or not recommended.
- Dosage: Individualized, typically 50mg sitagliptin and 80mg gliclazide daily, adjusted based on patient factors.
- Monitoring Parameters: Blood glucose, HbA1c, renal function.
Precautions
- General Precautions: Assess renal function, monitor blood glucose levels, and watch for signs of pancreatitis or allergic reactions.
- Specific Populations: Avoid in pregnancy and use with caution during breastfeeding. Consider age-related adjustments in elderly patients.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Gliclazide + Sitagliptin?
A: The dosage is individualized based on the patient’s current antidiabetic regimen, effectiveness, and tolerability. A common starting point is 50mg sitagliptin and 80mg gliclazide daily, adjusting as needed.
Q2: What are the main side effects of Gliclazide + Sitagliptin?
A: Common side effects include hypoglycemia, headache, nausea, and gastrointestinal issues. Rare but serious side effects include pancreatitis and allergic reactions.
Q3: Can Gliclazide + Sitagliptin be used during pregnancy?
A: Gliclazide is contraindicated in pregnancy. Sitagliptin has limited human data, but generally, alternative therapies are preferred. Consult a specialist.
Q4: How does Gliclazide + Sitagliptin differ from other antidiabetic medications?
A: It combines two different mechanisms of action – insulin stimulation (gliclazide) and incretin enhancement (sitagliptin) – to improve glycemic control.
Q5: How should the dose be adjusted in patients with renal impairment?
A: Dose reduction of sitagliptin is recommended. Gliclazide may need to be avoided or used with extreme caution.
Q6: What are the key drug interactions to be aware of?
A: Significant interactions can occur with CYP3A4 inhibitors/inducers, other antidiabetic medications (especially sulfonylureas and insulin), and alcohol.
Q7: What monitoring parameters are important for patients on Gliclazide + Sitagliptin?
A: Monitor blood glucose levels regularly, HbA1c for long-term control, and renal function, especially in elderly patients or those with pre-existing kidney problems.
Q8: What should I do if a patient experiences hypoglycemia while taking Gliclazide + Sitagliptin?
A: Follow standard hypoglycemia management protocols. Provide immediate glucose source if the patient is conscious, and administer glucagon or intravenous glucose if necessary. Review and adjust medication regimen.
Q9. When is the combination gliclazide + sitagliptin usually prescribed?
A: It’s generally prescribed for adults with type 2 diabetes when diet and exercise plus metformin are insufficient. It’s used to further improve glycemic control.
