Glipizide — Veterinary Vademecum Drug Reference

Dosage & Administration Guidelines

Species	Route	Dose	Frequency	Duration & Clinical Notes
Dog	PO	0.25-0.5 mg/kg (initial), up to 1 mg/kg if needed	q12h (every 12 hours)	Duration: Long-term; adjust based on glucose response Notes: Start with low dose and titrate based on blood glucose curves. Administer 30 minutes before meals to maximize effect.
Cat	PO	2.5-5 mg per cat (initial), up to 10 mg per cat	q12h (every 12 hours)	Duration: Long-term; adjust based on glucose response Notes: Start with 2.5 mg per cat twice daily. Monitor glucose curves and adjust dose. Some cats may require higher doses.
Horse	PO	Not established; not recommended	—	Not indicated for routine use in horses.
Cattle	PO	Not established; not recommended	—	Not indicated for food animals.
Small Ruminants	PO	Not established; not recommended	—	Not indicated.
Rabbit	PO	0.5-1 mg/kg (empirical)	q12h	Duration: Monitor response; adjust as needed Notes: Limited evidence; use with caution and monitor blood glucose closely.
Bird/Poultry	PO	Not established	—	Not indicated.
Exotic/Other	PO	Variable; based on species and response	q12h	Duration: Monitor response Notes: Use only if there is evidence of benefit; consult exotic animal specialist.

Clinical Indications & Species Uses

General Indications

Management of hyperglycemia in non-insulin-dependent diabetes mellitus (NIDDM) when beta-cell function is present

Dog (Canine)

Diabetes mellitus (non-insulin-dependent or type 2) in dogs with residual pancreatic beta-cell function
Adjunct to insulin therapy in some cases

Cat (Feline)

Diabetes mellitus (non-insulin-dependent or type 2) in cats with residual pancreatic beta-cell function
Adjunct to insulin therapy in some cases

Pharmacology & Mechanism of Action

Drug Class: Sulfonylurea | Pharmacological Group: Oral Hypoglycemic Agent

Mechanism of Action: Glipizide is a second-generation sulfonylurea that stimulates insulin release from pancreatic beta cells by binding to the sulfonylurea receptor (SUR1) on the ATP-sensitive potassium (K-ATP) channel. This binding closes the channel, leading to cell membrane depolarization, opening of voltage-gated calcium channels, and subsequent influx of calcium, which triggers exocytosis of insulin-containing granules. Additionally, glipizide may enhance peripheral insulin sensitivity and reduce hepatic glucose production, though these effects are secondary to its insulinotropic action. The drug requires functional pancreatic beta cells to exert its effect.

Pharmacodynamics: Glipizide lowers blood glucose by increasing insulin secretion, particularly in response to meals. It also reduces basal hepatic glucose output and may improve peripheral glucose utilization. The drug's effect is dose-dependent and is more pronounced in patients with residual beta-cell function. In veterinary patients, the response can be variable, and the drug is generally less effective than in humans due to species differences in beta-cell reserve and insulin resistance. Chronic use may lead to secondary failure as beta-cell function declines.

⚡ Pharmacokinetics Summary

Absorption: Glipizide is rapidly and completely absorbed from the gastrointestinal tract after oral administration. Food can delay absorption, but the overall extent is not significantly affected. Peak plasma concentrations occur within 1-3 hours in humans; similar kinetics are expected in dogs and cats, though specific veterinary data are limited.

Distribution: Glipizide is extensively bound to plasma proteins (approximately 92-99%), primarily albumin. It distributes into extracellular fluid and has a volume of distribution of about 0.1-0.2 L/kg in humans. In animals, distribution is likely similar, but specific data are sparse.

Metabolism: Glipizide is extensively metabolized in the liver, primarily by oxidation and hydroxylation, to inactive metabolites. The cytochrome P450 enzyme CYP2C9 is involved in its metabolism in humans; similar pathways are presumed in animals. Metabolites are excreted in urine and feces.

Excretion: Glipizide and its metabolites are excreted primarily in the urine (about 60-80%) and feces (about 20-40%). In humans, the elimination half-life is approximately 2-4 hours, but the duration of action can be longer due to tissue binding. In dogs, the half-life is reported to be around 3-4 hours; in cats, it may be slightly longer, but data are limited.

Half-Life: Dogs: ~3-4 hours; Cats: ~4-6 hours (estimated); Humans: 2-4 hours

Bioavailability: Oral bioavailability is nearly complete (approximately 100%) in humans; in animals, it is expected to be high, but food may delay absorption.

Protein Binding: 92-99% (primarily albumin)

Available Formulations & Strengths

Oral Tablet 5 mg, 10 mg (PO)

Oral Tablet (extended-release) 2.5 mg, 5 mg, 10 mg (PO)

Contraindications & Clinical Warnings

Contraindications:

Known hypersensitivity to glipizide or other sulfonylureas
Type 1 diabetes mellitus (insulin-dependent) or diabetic ketoacidosis
Severe hepatic or renal impairment
Pregnancy and lactation (safety not established)
Use in animals with no functional pancreatic beta cells

Warnings & Clinical Precautions:

Use with caution in animals with hepatic or renal disease; dose adjustment may be necessary.
Monitor blood glucose regularly to avoid hypoglycemia.
May cause weight gain due to increased insulin secretion.
Stress, infection, or surgery may alter insulin requirements; adjust therapy accordingly.
In cats, response may be poor if there is significant insulin resistance; consider insulin therapy if no improvement within 2-4 weeks.
Do not use in animals with a history of ketoacidosis.
Use with caution in geriatric animals.
May cause gastrointestinal upset; administer with food if this occurs.

Adverse Effects & Reactions

Common:

Hypoglycemia
Vomiting
Diarrhea
Anorexia
Lethargy

Serious / Severe:

Severe hypoglycemia leading to seizures or coma
Hepatotoxicity (rare)
Blood dyscrasias (rare)
Allergic reactions (rare)

Rare:

Cholestatic jaundice
Skin rashes
Photosensitivity
Disulfiram-like reaction with alcohol (not relevant in animals)

Key Drug Interactions

Interacting Drug / Class	Clinical Effect & Mechanism	Severity
Beta-blockers	May mask signs of hypoglycemia and impair glucose counter-regulation.	Moderate
Corticosteroids	May increase blood glucose, reducing the effectiveness of glipizide.	Moderate
NSAIDs (e.g., aspirin, phenylbutazone)	May potentiate the hypoglycemic effect by displacing glipizide from protein binding or reducing renal excretion.	Moderate
Sulfonamides	May enhance hypoglycemic effect.	Moderate
Warfarin	May increase anticoagulant effect; monitor prothrombin time.	Moderate
Diuretics (thiazides, furosemide)	May increase blood glucose, reducing glipizide efficacy.	Mild
Insulin	Additive hypoglycemic effect; dose adjustment may be needed.	High

Overdose & Toxicity Management

Signs of Toxicity:

Hypoglycemia (weakness, lethargy, ataxia, tremors, seizures, coma)
Vomiting
Anorexia
Hypothermia

Emergency Treatment Protocol: For mild hypoglycemia, administer oral glucose or corn syrup. For severe hypoglycemia (seizures or coma), administer intravenous dextrose (0.5-1 g/kg as a 25-50% solution) as a bolus, followed by a continuous infusion of 2.5-5% dextrose if needed. Monitor blood glucose closely. In cases of massive overdose, consider gastric lavage if recent ingestion, and administer activated charcoal. Provide supportive care and monitor for hepatic or renal effects.

Food Animal Withdrawal Times

Not approved for use in food animals; withdrawal times not established. Do not use in animals intended for food.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature (20-25°C, 68-77°F).

Handling & Special Conditions: Protect from moisture. Keep container tightly closed.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Not FDA-approved for veterinary use; approved for human use.

Extra-Label (Off-Label) Use: In the US, glipizide is not FDA-approved for veterinary use; use in animals is extra-label. Under AMDUCA, extra-label use is permitted in non-food animals by or on the order of a veterinarian within a valid VCPR. Use in food animals is prohibited due to lack of withdrawal times.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Glipizide is an oral hypoglycemic agent used primarily in dogs and cats with type 2 diabetes mellitus when there is residual pancreatic beta-cell function. It is not a substitute for insulin in insulin-dependent diabetes. In cats, response is often poor, and many cats eventually require insulin therapy. In dogs, it is rarely effective and is not commonly used. The drug should be used with careful monitoring of blood glucose, and owners should be educated on signs of hypoglycemia. Dose adjustments should be based on serial blood glucose curves. Because of the risk of hypoglycemia, it is essential to ensure regular feeding schedules. Glipizide may be used as an adjunct to insulin in some cases, but combination therapy requires careful monitoring. In exotic species, use is anecdotal and should be guided by a specialist. Always consider the cost-benefit and alternative therapies (e.g., insulin) before initiating glipizide.

References & Literature

📚 Plumb's Veterinary Drug Handbook
📚 Papich Veterinary Pharmacology and Therapeutics
📚 Compendium of Veterinary Products (CVP)