Glipizide

Usage

• Glipizide is prescribed for the management of type 2 diabetes mellitus as an adjunct to diet and exercise to improve glycemic control in adults. It is not indicated for type 1 diabetes mellitus or diabetic ketoacidosis.
• Pharmacological Classification: Sulfonylurea (second-generation).
• Mechanism of Action: Glipizide primarily works by stimulating insulin release from the pancreatic beta cells. This action is dependent on functioning beta cells in the pancreatic islets. It may also decrease hepatic glucose production and increase insulin receptor sensitivity.

Alternate Names

• International/Regional Variations: Minodiab (India)
• Brand Names: Glucotrol, Glucotrol XL

How It Works

• Pharmacodynamics: Glipizide binds to sulfonylurea receptors on the pancreatic beta-cell membrane, closing ATP-sensitive potassium channels. This depolarizes the beta-cell membrane, opening voltage-gated calcium channels and increasing intracellular calcium, which stimulates insulin release.
• Pharmacokinetics:
  • Absorption: Well-absorbed from the gastrointestinal tract. Immediate-release formulations reach peak plasma concentrations in 1-3 hours, while extended-release formulations peak in 4-6 hours. Food delays absorption.
  • Metabolism: Primarily metabolized in the liver by CYP2C9 to inactive metabolites.
  • Elimination: Excreted mainly in the urine (approximately 90%), with a small amount in feces. The elimination half-life is 2-4 hours for immediate-release and 7-10 hours for extended-release formulations.

Dosage

Standard Dosage

Adults:

• Immediate-Release (IR): Initial dose: 5 mg orally once daily, 30 minutes before breakfast. Dosage can be increased in 2.5-5 mg increments every several days based on blood glucose response. The maximum recommended dose is 40 mg daily. Doses greater than 15 mg should be divided and administered twice daily.

• Extended-Release (ER): Initial dose: 5 mg orally once daily with breakfast. Dosage can be adjusted based on blood glucose response, not more frequently than every 7 days. The maximum recommended dose is 20 mg once daily.

Children: Safety and efficacy have not been established in pediatric patients.

Special Cases:

• Elderly Patients: Initiate at 2.5 mg daily (IR or ER) due to increased risk of hypoglycemia. Titrate cautiously.
• Patients with Renal Impairment: In patients with a glomerular filtration rate (GFR) less than 50 mL/min, consider a 50% dose reduction. Titrate cautiously.
• Patients with Hepatic Dysfunction: Initiate at 2.5 mg daily with the immediate-release formulation. Extended-release is not recommended. Titrate cautiously.
• Patients with Comorbid Conditions: Use with caution and monitor closely for hypoglycemia in patients with other medical conditions, especially cardiovascular or adrenal disease.

Clinical Use Cases

Glipizide is not typically used in clinical scenarios like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations like cardiac arrest. For acute management of hyperglycemia in these settings, insulin therapy is typically preferred.

Side Effects

Common Side Effects:

• Hypoglycemia
• Nausea
• Headache
• Dizziness
• Weight gain

Rare but Serious Side Effects:

• Severe hypoglycemia
• Hepatotoxicity (rare)
• Hemolytic anemia (in patients with G6PD deficiency)
• Disulfiram-like reaction (with alcohol ingestion)

Long-Term Effects:

• Potential for weight gain with long-term use
• Possible secondary failure, meaning the drug may become less effective over time

Contraindications

• Hypersensitivity to glipizide or other sulfonylureas.
• Type 1 diabetes mellitus
• Diabetic ketoacidosis
• Severe renal or hepatic impairment

Drug Interactions

• CYP2C9 Inhibitors: Increase glipizide levels and risk of hypoglycemia. Examples include fluconazole, azole antifungals, some antibiotics.
• CYP2C9 Inducers: Decrease glipizide levels and may reduce efficacy. Examples include rifampin, phenytoin.
• Beta-Blockers: Can mask the symptoms of hypoglycemia.
• Alcohol: May cause a disulfiram-like reaction.
• Other Antidiabetic Agents: Increased risk of hypoglycemia.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: C (first trimester) and D (second and third trimesters). Glipizide should be avoided during pregnancy, especially in the second and third trimesters. Insulin is the preferred agent for managing diabetes in pregnant women.
• Breastfeeding: Glipizide is excreted in breast milk. Caution should be exercised when administering to breastfeeding women.

Drug Profile Summary

• Mechanism of Action: Stimulates insulin release from pancreatic beta cells.
• Side Effects: Hypoglycemia, nausea, headache, weight gain.
• Contraindications: Hypersensitivity to sulfonylureas, type 1 diabetes, diabetic ketoacidosis.
• Drug Interactions: CYP2C9 inhibitors, beta-blockers, alcohol.
• Pregnancy & Breastfeeding: Avoid during pregnancy. Use caution during breastfeeding.
• Dosage: IR: 5-40 mg daily; ER: 5-20 mg daily.
• Monitoring Parameters: Blood glucose, HbA1c.

Popular Combinations

• Glipizide + Metformin: This combination is frequently used to achieve better glycemic control than with either drug alone.

Precautions

• General Precautions: Assess renal and hepatic function before and during treatment. Monitor blood glucose regularly. Educate patients about hypoglycemia symptoms and management.
• Specific Populations: Use with caution in elderly patients and those with renal or hepatic impairment. Avoid in pregnancy. Exercise caution during breastfeeding.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Glipizide?

A: IR: Initial dose is 5 mg daily 30 minutes before breakfast. The maximum dose is 40 mg/day. ER: Initial dose is 5 mg daily with breakfast. The maximum dose is 20 mg/day. Adjust dosage based on blood glucose response.

Q2: How does Glipizide differ from other sulfonylureas?

A: Glipizide is a second-generation sulfonylurea and is considered more potent than first-generation agents. It has a shorter half-life than some other sulfonylureas, potentially reducing the risk of prolonged hypoglycemia.

Q3: Can Glipizide be used in patients with renal impairment?

A: Use with caution. Reduce the dose and titrate conservatively in patients with a GFR <50 mL/min.

Q4: What are the common side effects of Glipizide?

A: The most common side effect is hypoglycemia. Other side effects include nausea, headache, dizziness, and weight gain.

Q5: What are the contraindications to using Glipizide?

A: Contraindications include known hypersensitivity to sulfonylureas, type 1 diabetes mellitus, diabetic ketoacidosis, and severe renal or hepatic impairment.

Q6: Can Glipizide be used during pregnancy?

A: Glipizide is generally avoided during pregnancy, particularly in the second and third trimesters. Insulin is the preferred agent for managing diabetes during pregnancy.

Q7: How should Glipizide be taken?

A: IR tablets should be taken 30 minutes before a meal. ER tablets should be taken with breakfast or the first meal of the day.

Q8: What should I do if a patient experiences hypoglycemia while taking Glipizide?

A: For mild hypoglycemia, administer oral glucose (e.g., glucose tablets, juice). For severe hypoglycemia with loss of consciousness or neurological symptoms, administer glucagon or intravenous glucose. Monitor the patient closely for recurrence of hypoglycemia.

Q9: Can Glipizide be used in combination with other antidiabetic medications?

A: Yes, glipizide can be combined with other antidiabetic medications, such as metformin, but this increases the risk of hypoglycemia. Start at the lowest recommended dose of the additional agent and monitor closely.