Usage
- Dapagliflozin + Gliclazide is prescribed for type 2 diabetes mellitus in adults to improve glycemic control when metformin monotherapy is insufficient. It is specifically indicated for patients who have inadequate glycemic control with metformin alone or who are intolerant to metformin.
- Pharmacological Classification: Antidiabetic combination containing a sodium-glucose co-transporter 2 (SGLT2) inhibitor (Dapagliflozin) and a sulfonylurea (Gliclazide).
- Mechanism of Action: Dapagliflozin inhibits SGLT2 in the kidneys, increasing urinary glucose excretion and lowering blood glucose levels. Gliclazide stimulates insulin release from pancreatic beta-cells, also reducing blood glucose.
Alternate Names
- This combination medication currently does not have an International Nonproprietary Name (INN). It is referred to by its constituent drug names.
- Brand Names: While specific brand names can vary by region, examples include Xigduo XR (Fixed Dose Combination).
How It Works
- Pharmacodynamics: Dapagliflozin works independently of insulin to promote glucose excretion. Gliclazide enhances insulin secretion, resulting in decreased hepatic glucose production and improved peripheral insulin sensitivity. The combined effect results in improved glycemic control.
- Pharmacokinetics:
- Dapagliflozin: Absorption is rapid, with peak plasma concentration occurring within 2 hours. It is primarily eliminated through renal excretion, with minor hepatic metabolism.
- Gliclazide: Almost completely absorbed after oral administration. It is metabolized in the liver and its metabolites are excreted in urine and feces.
- Mode of Action: Dapagliflozin inhibits SGLT2 in the renal proximal tubules, preventing glucose reabsorption. Gliclazide binds to sulfonylurea receptors on pancreatic beta-cells, blocking ATP-sensitive potassium channels, leading to depolarization and insulin release.
- Elimination Pathways: Dapagliflozin is primarily excreted unchanged in the urine. Gliclazide is metabolized in the liver and excreted in urine and feces.
Dosage
Standard Dosage
Adults:
- The starting dose is typically Dapagliflozin 5 mg + Gliclazide 30 mg Modified Release (MR) once daily, taken with breakfast. The dose may be titrated up to Dapagliflozin 10 mg + Gliclazide MR up to 120 mg depending on individual glycemic response.
- It is essential to titrate Gliclazide individually based on the patient’s current Gliclazide dose if transferring from Gliclazide monotherapy.
Children:
- This combination is not recommended for use in children due to limited safety and efficacy data.
Special Cases:
- Elderly Patients: Initiate at the lowest dose and titrate cautiously, considering renal function.
- Patients with Renal Impairment:
- Moderate (eGFR 30-60 mL/min/1.73 m²): Dapagliflozin 5 mg once daily. Gliclazide dose should be adjusted based on renal function.
- Severe (eGFR <30 mL/min/1.73 m²): Contraindicated.
- Patients with Hepatic Dysfunction: Gliclazide dose adjustment might be needed. Close monitoring is necessary. Use with caution.
- Patients with Comorbid Conditions: Careful assessment is required, particularly in patients with cardiovascular disease, as Dapagliflozin can cause volume depletion.
Clinical Use Cases
- This medication is not indicated for use in intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its usage is limited to chronic management of type 2 diabetes.
Dosage Adjustments
- Dose adjustments may be based on renal function, hepatic function, concomitant medications, and individual glycemic response.
Side Effects
Common Side Effects
- Hypoglycemia (especially when used with insulin or other antidiabetic medications)
- Urinary tract infections
- Genital mycotic infections
- Increased urination
- Nasopharyngitis
- Back pain
Rare but Serious Side Effects
- Diabetic ketoacidosis (DKA)
- Acute kidney injury
- Severe hypoglycemia
- Fournier’s gangrene (necrotizing fasciitis of the perineum)
- Angioedema
Long-Term Effects
- Potential for bone fractures with prolonged use of SGLT2 inhibitors.
Adverse Drug Reactions (ADR)
- Severe hypoglycemia
- Angioedema
- DKA
Contraindications
- Type 1 diabetes mellitus
- Diabetic ketoacidosis
- Severe renal impairment (eGFR <30 mL/min/1.73 m²)
- End-stage renal disease (ESRD)
- Hypersensitivity to dapagliflozin, gliclazide, or any component of the formulation
Drug Interactions
- Insulin or other Sulfonylureas: Increased risk of hypoglycemia. Dose adjustment might be needed.
- Diuretics: Increased risk of dehydration and hypotension.
- CYP450 Inducers (e.g., rifampicin): Decreased dapagliflozin efficacy.
- Alcohol: May potentiate the hypoglycemic effects.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Category C (Dapagliflozin), Category C (Gliclazide). Contraindicated. Not recommended as it may cause fetal harm.
- Breastfeeding: Contraindicated. Both drugs are excreted in breast milk and can cause neonatal hypoglycemia.
Drug Profile Summary
- Mechanism of Action: Increases urinary glucose excretion (dapagliflozin) and stimulates insulin release (gliclazide).
- Side Effects: Hypoglycemia, urinary tract infections, genital infections.
- Contraindications: Type 1 diabetes, DKA, severe renal impairment, pregnancy, breastfeeding.
- Drug Interactions: Insulin, sulfonylureas, diuretics, rifampicin.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Start with Dapagliflozin 5mg/Gliclazide 30mg MR, titrate as needed. Max: Dapagliflozin 10 mg/ Gliclazide 120 mg.
- Monitoring Parameters: HbA1c, fasting and postprandial glucose, renal function, blood pressure.
Popular Combinations
- Dapagliflozin + Metformin: This fixed-dose combination can be used in patients requiring further glycemic control.
Precautions
- General Precautions: Monitor renal function, electrolytes, blood pressure, and signs of dehydration.
- Specific Populations:
- Pregnant Women: Contraindicated.
- Breastfeeding Mothers: Contraindicated.
- Children & Elderly: Not recommended in children. Initiate with low doses and titrate cautiously in the elderly.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Dapagliflozin + Gliclazide?
A: The usual starting dose is Dapagliflozin 5mg + Gliclazide 30mg Modified Release once daily. It can be increased to 10mg/120mg based on glycemic control.
Q2: Can this combination be used in patients with type 1 diabetes?
A: No, it is contraindicated in type 1 diabetes.
Q3: What are the common side effects?
A: Common side effects include hypoglycemia, urinary tract infections, genital mycotic infections, and increased urination.
Q4: Are there any serious side effects I should be aware of?
A: Yes. Diabetic ketoacidosis, though rare, is a serious potential side effect. Other rare side effects include acute kidney injury and Fournier’s gangrene.
Q5: Can this combination be used during pregnancy or breastfeeding?
A: No, it is contraindicated during pregnancy and breastfeeding.
Q6: How does dapagliflozin interact with other antidiabetic medications?
A: Combining dapagliflozin with insulin or sulfonylureas can increase the risk of hypoglycemia. Careful dose adjustment may be necessary.
Q7: What should I monitor in patients taking this combination?
A: Regularly monitor HbA1c, fasting and postprandial glucose, renal function, blood pressure, and signs of dehydration.
Q8: What are the contraindications for this combination?
A: Contraindications include type 1 diabetes, diabetic ketoacidosis, severe renal impairment (eGFR < 30ml/min/1.73m2), end-stage renal disease, and hypersensitivity to dapagliflozin or gliclazide.
Q9: Should the dose be adjusted in elderly patients?
A: Yes, elderly patients should generally be started on a lower dose, and the dose should be titrated cautiously due to potential age-related decline in renal function.
