Glucotrol XL (glipizide) is an extended-release oral antihyperglycemic agent from the sulfonylurea class, specifically engineered for the management of type 2 diabetes mellitus. It functions by stimulating insulin release from the pancreatic beta cells and improving peripheral glucose utilization. This formulation provides a steady 24-hour drug delivery, facilitating consistent blood glucose lowering with a single daily dose, which supports long-term therapeutic adherence and metabolic stability. It is indicated as an adjunct to diet and exercise when glycemic control is not achieved by lifestyle modifications alone.

Features

• Active Pharmaceutical Ingredient: Glipizide.
• Dosage Form: Extended-release (XL) tablet for oral administration.
• Available Strengths: 2.5 mg, 5 mg, and 10 mg tablets.
• Mechanism of Action: Second-generation sulfonylurea that primarily lowers blood glucose by stimulating insulin secretion from functional pancreatic beta cells.
• Pharmacokinetics: Designed for once-daily dosing; utilizes a gastrointestinal therapeutic system (GITS) for controlled, gradual release over approximately 24 hours.
• Bioavailability: Nearly 100% following oral administration.
• Peak Plasma Time: Achieved within 6-12 hours after dosing in the fasting state.
• Elimination Half-life: 2-4 hours; the extended-release mechanism decouples pharmacokinetics from the pharmacodynamic effect.
• Excretion: Primarily hepatic metabolism to inactive metabolites, with excretion via the kidney (80-90%) and in feces (10-20%).

Benefits

• Provides sustained 24-hour glycemic control from a single daily dose, enhancing patient convenience and compliance.
• Effectively lowers both fasting and postprandial blood glucose levels, contributing to a reduced HbA1c.
• The controlled-release profile minimizes peak-to-trough plasma level fluctuations, potentially reducing the risk of hypoglycemic events compared to immediate-release formulations.
• Serves as a effective monotherapy or can be used in combination with other antihyperglycemic agents like metformin for synergistic effects.
• Helps mitigate the long-term microvascular and macrovascular complications associated with poorly controlled type 2 diabetes.

Common use

Glucotrol XL is commonly prescribed for the management of hyperglycemia in patients with type 2 diabetes mellitus. It is utilized when therapeutic goals for glycemic control are not met through diet, exercise, and weight loss alone. It is suitable for both newly diagnosed patients and those transitioning from other antihyperglycemic regimens seeking the convenience of once-daily dosing and a smoother pharmacokinetic profile. Its use is integral to a comprehensive diabetes management plan.

Dosage and direction

The recommended starting dose is 5 mg once daily, taken with breakfast. Dosage adjustments should be made in increments of 5 mg, at intervals of no less than 7 days, based on blood glucose response. The maximum recommended daily dose is 20 mg. The tablet must be swallowed whole and must not be crushed, chewed, or divided. Administration with a meal is advised to optimize gastrointestinal tolerance and ensure consistent absorption. It is critical that dosing is individualized to achieve the lowest effective dose for the patient.

Precautions

• Hypoglycemia: All sulfonylureas, including Glucotrol XL, can cause severe hypoglycemia. Risk is increased by skipped meals, strenuous exercise, alcohol consumption, renal or hepatic impairment, and use of other glucose-lowering drugs.
• Hemolytic Anemia: Use with caution in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, as sulfonylureas have been associated with hemolytic anemia in this group.
• Hepatic and Renal Impairment: Metabolism and excretion may be altered. Patients with impaired liver or kidney function should be initiated on lower doses and monitored closely for hypoglycemia; may be contraindicated in severe impairment.
• Stress: In patients exposed to stress (e.g., fever, trauma, infection, surgery), a loss of glycemic control may occur, potentially necessitating temporary discontinuation and initiation of insulin therapy.
• Photosensitivity: Photosensitivity reactions have been reported with sulfonylureas; patients should be advised to use sun protection.
• Cardiovascular Mortality: The potential for increased cardiovascular mortality, as observed with other sulfonylureas, should be considered.

Contraindications

• Known hypersensitivity to glipizide, any other sulfonylurea, or any component of the formulation.
• Type 1 diabetes mellitus or diabetic ketoacidosis, with or without coma. (These conditions require insulin therapy.)
• Concomitant use with bosentan.
• Severe renal or hepatic impairment, due to significantly increased risk of prolonged hypoglycemia.

Possible side effect

The following adverse reactions have been reported. Common side effects (≥1%) include:

• Hypoglycemia
• Dizziness
• Diarrhea
• Nervousness
• Tremor
• Flatulence
• Asthenia
• Headache

Less common but serious side effects include:

• Severe hypoglycemia (requiring assistance)
• Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)
• Disulfiram-like reactions with alcohol
• Hepatic porphyria
• Photosensitivity reactions
• Blood dyscrasias (leukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia, aplastic anemia)
• Allergic skin reactions (e.g., urticaria, maculopapular eruptions)
• Hyponatremia

Drug interaction

Glipizide’s hypoglycemic effect may be potentiated (increased risk of hypoglycemia) by:

• Other antidiabetic agents (insulin, metformin, GLP-1 RAs)
• NSAIDs and other protein-bound drugs (salicylates, sulfonamides, chloramphenicol, probenecid, coumarins, MAO inhibitors, beta-adrenergic blocking agents)
• Fluconazole
• ACE inhibitors
• Alcohol

Glipizide’s hypoglycemic effect may be antagonized (increased risk of hyperglycemia) by:

• Corticosteroids
• Phenothiazines
• Thyroid products
• Estrogens, oral contraceptives
• Phenytoin
• Nicotinic acid
• Sympathomimetics
• Calcium channel blocking drugs
• Isoniazid
• Thiazides and other diuretics

Beta-blockers may mask the tachycardic signs of hypoglycemia and potentiate the hypoglycemic effect.

Missed dose

If a dose is missed, it should be taken as soon as remembered that day. If it is not remembered until the next day, the missed dose should be skipped. The regular dosing schedule should be resumed the next day. The dose should not be doubled to make up for a missed dose, as this increases the risk of hypoglycemia.

Overdose

Sulfonylurea overdose can produce severe and prolonged hypoglycemia, presenting as sweating, tremor, blurred vision, hunger, confusion, seizures, coma, and death. Management involves immediate glucose administration (oral dextrose for a conscious patient, intravenous glucose or glucagon injection for an unconscious patient). Continuous glucose infusion and frequent monitoring are required for a minimum of 24-48 hours, as hypoglycemia may recur after initial treatment. Hospitalization is critical. Hemodialysis is unlikely to be beneficial due to high protein binding.

Storage

Store at controlled room temperature, 20°C to 25°C (68°F to 77°F), with excursions permitted between 15°C and 30°C (59°F and 86°F). Protect from moisture and light. Keep the medication in its original blister pack or bottle. Keep all medications out of the reach of children and pets. Do not flush unused medication; dispose of it according to local guidelines or via a medicine take-back program.

Disclaimer

This information is for educational and informational purposes only and does not constitute medical advice. It is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or before starting any new treatment. Never disregard professional medical advice or delay in seeking it because of something you have read here. The information provided is based on the drug’s prescribing information but may not be exhaustive.

Reviews

“Glucotrol XL has been a cornerstone of my type 2 diabetes management for over five years. The once-daily dosing is incredibly convenient and has made adherence effortless. My HbA1c has remained consistently below 7.0% with minimal fluctuations in my daily glucose readings. I experienced some mild dizziness during the initial titration period, but this subsided. It has provided stable and reliable control with a very low incidence of hypoglycemic events for me.” – M.K., 68

“As an endocrinologist, I find Glucotrol XL to be a valuable tool in my arsenal, particularly for patients who need an additional agent beyond metformin. The extended-release mechanism offers a more physiological insulin secretion pattern compared to immediate-release sulfonylureas, which I believe contributes to its favorable efficacy and safety profile in appropriate patients. It is especially useful for those who struggle with postprandial hyperglycemia. Careful patient selection and education on hypoglycemia recognition remain paramount.” – Dr. E. Vance, MD