Usage
- Glibenclamide is prescribed for the treatment of type 2 diabetes mellitus, specifically in patients whose blood sugar levels are not adequately controlled by diet and exercise alone. It is often used as a second-line treatment when metformin is not tolerated or contraindicated, or in combination with metformin when the latter alone is insufficient.
- Pharmacological Classification: Sulfonylurea, Antidiabetic Agent
- Mechanism of Action: Glibenclamide stimulates insulin release from pancreatic beta-cells. It binds to and closes ATP-sensitive potassium channels on the beta-cell membrane, which leads to membrane depolarization and opening of voltage-dependent calcium channels. The influx of calcium ions triggers insulin secretion. Glibenclamide also increases peripheral insulin sensitivity and reduces hepatic glucose output.
Alternate Names
- International/Regional Variations: Glyburide (primarily used in the US and Canada)
- Brand Names: Daonil, Diabeta, Glynase, Micronase. Several combination products with metformin are also available under different brand names.
How It Works
- Pharmacodynamics: Glibenclamide’s primary effect is to lower blood glucose levels by stimulating insulin release. It improves peripheral glucose utilization and reduces hepatic glucose production.
- Pharmacokinetics:
- Absorption: Glibenclamide is well-absorbed orally. Taking it with food can enhance absorption.
- Metabolism: Primarily metabolized in the liver by CYP2C9 to inactive metabolites.
- Elimination: Excreted mainly in the urine and bile. Dosage adjustments may be required in patients with hepatic or renal insufficiency.
- Mode of Action: Binds to sulfonylurea receptors (SUR1) on the ATP-sensitive potassium channels of pancreatic beta-cells, inhibiting the channel and leading to insulin release.
- Receptor Binding/Enzyme Inhibition: Inhibits ATP-sensitive potassium channels.
- Elimination Pathways: Primarily hepatic metabolism followed by renal and biliary excretion.
Dosage
Standard Dosage
Adults:
- Initial: 2.5-5 mg orally once daily, taken with the first main meal.
- Maintenance: 1.25-20 mg orally once daily or in two divided doses (for doses >10mg). The maximum dose is 20 mg daily. Doses should be titrated upwards based on blood glucose response, typically in increments of 2.5 mg weekly.
Children:
- Glibenclamide is generally not recommended for children. Safety and efficacy in pediatric populations have not been established.
Special Cases:
- Elderly Patients: Start with a lower dose (1.25 mg/day for non-micronized tablets or 0.75 mg/day for micronized tablets), titrating cautiously due to increased risk of hypoglycemia.
- Patients with Renal Impairment: Use with caution in patients with creatinine clearance less than 50 mL/min. Significant renal impairment is a relative contraindication.
- Patients with Hepatic Dysfunction: Use with caution and at lower doses; avoid use in severe hepatic impairment.
- Patients with Comorbid Conditions: Patients with adrenal or pituitary insufficiency or conditions that increase the risk of hypoglycemia require careful monitoring.
Clinical Use Cases
Glibenclamide is specifically indicated for the management of type 2 diabetes. It is not typically used in the context of intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. For such situations, insulin therapy is preferred.
Dosage Adjustments
Dose adjustments may be necessary in patients with renal/hepatic impairment, elderly patients, or patients with certain comorbid conditions.
Side Effects
Common Side Effects:
- Hypoglycemia (low blood sugar)
- Nausea, heartburn, stomach upset, diarrhoea
- Weight gain
- Headache, dizziness, weakness
Rare but Serious Side Effects:
- Severe hypoglycemia
- Hepatotoxicity (liver damage)
- Blood disorders (thrombocytopenia, leukopenia, agranulocytosis)
- Allergic reactions (skin rash, itching, swelling)
Long-Term Effects:
- Increased risk of cardiovascular mortality has been suggested in some studies, although evidence is not conclusive.
Adverse Drug Reactions (ADR):
- Severe hypoglycemia requiring medical intervention
- Hepatotoxicity
- Hematological abnormalities
Contraindications
- Hypersensitivity to glibenclamide, other sulfonylureas, or sulfonamides
- Type 1 diabetes mellitus
- Diabetic ketoacidosis, diabetic coma
- Severe renal or hepatic impairment
- Porphyria
- Concomitant use with bosentan
Drug Interactions
- CYP450 Interactions: Glibenclamide is metabolized by CYP2C9. Drugs that inhibit or induce CYP2C9 can alter glibenclamide levels.
- Other Drug Interactions:
- NSAIDs, beta-blockers, alcohol, some antibiotics (e.g., fluoroquinolones, macrolides) can enhance the hypoglycemic effect.
- Corticosteroids, thiazide diuretics can decrease the hypoglycemic effect.
- Bosentan increases the risk of hepatotoxicity.
- Colesevelam can reduce glibenclamide absorption.
- Food and Lifestyle Factors: Alcohol can potentiate the hypoglycemic effect and can cause a disulfiram-like reaction.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Category C (or B by some manufacturers). Not generally recommended during pregnancy, especially during the first trimester. Insulin is the preferred agent for managing diabetes during pregnancy.
- Breastfeeding: Small amounts of glibenclamide are excreted in breast milk. Use with caution during breastfeeding. Monitor the infant for signs of hypoglycemia.
Drug Profile Summary
- Mechanism of Action: Stimulates insulin release from pancreatic beta-cells.
- Side Effects: Hypoglycemia, nausea, weight gain.
- Contraindications: Type 1 diabetes, diabetic ketoacidosis, severe renal/hepatic impairment.
- Drug Interactions: NSAIDs, beta-blockers, alcohol, bosentan.
- Pregnancy & Breastfeeding: Use with caution; generally avoided in pregnancy.
- Dosage: 2.5-20 mg daily.
- Monitoring Parameters: Blood glucose levels, HbA1c.
Popular Combinations
- Metformin: The combination of glibenclamide and metformin is frequently used to achieve better glycemic control when metformin alone is insufficient.
Precautions
- Monitor blood glucose and HbA1c levels regularly.
- Educate patients about the signs and symptoms of hypoglycemia.
- Patients with G6PD deficiency should not use this drug.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Glibenclamide?
A: The initial dose is typically 2.5-5 mg daily, taken with the first main meal. The maintenance dose can range from 1.25-20 mg/day, adjusted based on blood glucose response. Higher doses may be divided.
Q2: What are the common side effects?
A: Common side effects include hypoglycemia, nausea, heartburn, weight gain, and gastrointestinal disturbances.
Q3: Can Glibenclamide be used during pregnancy?
A: It is generally not recommended during pregnancy, particularly in the first trimester, due to potential risks to the fetus. Insulin is the preferred agent.
Q4: How does Glibenclamide work?
A: It stimulates insulin release from the pancreas and increases tissue sensitivity to insulin.
Q5: What are the contraindications?
A: Type 1 diabetes, diabetic ketoacidosis, severe renal or hepatic disease, porphyria, hypersensitivity to sulfonylureas.
Q6: What are the signs of hypoglycemia?
A: Symptoms may include sweating, tremor, weakness, dizziness, confusion, headache, hunger, and palpitations.
Q7: What should I do if a patient experiences hypoglycemia?
A: Mild hypoglycemia can be managed with oral glucose (e.g., glucose tablets, fruit juice). Severe hypoglycemia may require intravenous glucose or glucagon.
Q8: Does Glibenclamide interact with other medications?
A: Yes, it interacts with many medications, including NSAIDs, beta-blockers, some antibiotics, and alcohol. It’s important to check for potential drug interactions before prescribing.
Q9: Are there any long-term risks associated with Glibenclamide?
A: Some studies suggest a potential increased risk of cardiovascular events with long-term use. However, this is not definitively established.
A: Yes, the combination is often prescribed for better blood sugar control.
