Introduction
Glucotrol (glipizide) is a second-generation sulfonylurea oral antihyperglycemic agent used in the management of type 2 diabetes mellitus. As an insulin secretagogue, it stimulates pancreatic beta cells to release insulin, helping to control blood glucose levels in appropriate patients.
Mechanism of Action
Glucotrol primarily works by binding to ATP-sensitive potassium channels on pancreatic beta cells, leading to cell membrane depolarization, calcium influx, and subsequent insulin secretion. This mechanism is glucose-dependent, with greater effect at higher blood glucose concentrations. Unlike first-generation sulfonylureas, glipizide has minimal effect on cardiovascular potassium channels, resulting in a more favorable side effect profile.
Indications
- Management of type 2 diabetes mellitus as an adjunct to diet and exercise
- May be used as monotherapy or in combination with other antihyperglycemic agents when glycemic control is not achieved with single agents
Dosage and Administration
Initial dose: 5 mg once daily, 30 minutes before breakfast Maintenance dose: 5-40 mg daily (maximum recommended dose) Dosage adjustment: Increase by 2.5-5 mg at weekly intervals based on glycemic response Elderly patients: Start with 2.5 mg daily Renal impairment: Use with caution; consider alternative agents in severe impairment Hepatic impairment: Use with caution; monitor closelyPharmacokinetics
Absorption: Rapid and nearly complete (90-100% bioavailability); food decreases absorption rate but not extent Distribution: Protein binding: 92-99%; Volume of distribution: 10-15 L Metabolism: Hepatic metabolism via cytochrome P450 2C9 to inactive metabolites Elimination: Half-life: 2-4 hours; duration of action: 12-24 hours; excretion primarily renal (80-90% as metabolites) Onset of action: Within 30 minutes; peak effect: 1-3 hoursContraindications
- Known hypersensitivity to glipizide or sulfonylureas
- Type 1 diabetes mellitus
- Diabetic ketoacidosis
- Severe renal or hepatic impairment
- Concomitant use with bosentan
Warnings and Precautions
Hypoglycemia: Risk increased with elderly patients, renal/hepatic impairment, malnutrition, and alcohol use Cardiovascular mortality: Increased cardiovascular mortality reported with other sulfonylureas Hemolytic anemia: Possible in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency Syndrome of inappropriate antidiuretic hormone (SIADH): Water retention and hyponatremia reported Photosensitivity: May cause photosensitivity reactions Hepatic effects: May cause elevated liver enzymes; discontinue if jaundice occursDrug Interactions
Strong CYP2C9 inhibitors: Fluconazole, amiodarone - may increase glipizide levels Beta-blockers: May mask hypoglycemia symptoms Alcohol: May cause disulfiram-like reaction and increase hypoglycemia risk Warfarin: Potential for increased anticoagulant effect Thiazides, corticosteroids, phenytoin: May decrease hypoglycemic effect MAO inhibitors, salicylates, sulfonamides: May increase hypoglycemic effectAdverse Effects
Common (>10%): Hypoglycemia, dizziness, nausea Less common (1-10%): Headache, diarrhea, constipation, weight gain Rare (<1%):- Hematologic: Leukopenia, thrombocytopenia, hemolytic anemia
- Hepatic: Elevated transaminases, hepatitis
- Dermatologic: Photosensitivity, rash, pruritus
- Gastrointestinal: Cholestatic jaundice
- Endocrine: SIADH
Monitoring Parameters
- Fasting blood glucose and HbA1c (every 3 months until stable)
- Renal function (serum creatinine) at baseline and periodically
- Liver function tests at baseline and periodically
- Signs and symptoms of hypoglycemia
- Weight changes
- Complete blood count annually
Patient Education
- Take medication 30 minutes before breakfast or first main meal
- Recognize symptoms of hypoglycemia (sweating, shaking, hunger, confusion)
- Carry glucose tablets or quick sugar source for hypoglycemia treatment
- Do not skip meals while taking Glucotrol
- Avoid excessive alcohol consumption
- Regular blood glucose monitoring as directed
- Report any unusual symptoms, especially jaundice, dark urine, or unusual bleeding/bruising
- Use sun protection due to photosensitivity risk
- Inform all healthcare providers about Glucotrol use before procedures
References
1. American Diabetes Association. (2023). Standards of Medical Care in Diabetes. Diabetes Care, 46(Supplement_1). 2. Glucotrol [package insert]. New York, NY: Pfizer Labs; 2022. 3. Bennett WL, et al. (2011). Comparative effectiveness and safety of medications for type 2 diabetes. Annals of Internal Medicine, 154(9), 602-613. 4. Inzucchi SE, et al. (2015). Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach. Diabetes Care, 38(1), 140-149. 5. Lexicomp Online. Glipizide: Drug Information. Wolters Kluwer Clinical Drug Information. 6. U.S. Food and Drug Administration. (2022). Glucotrol prescribing information.