Insulin (Regular, NPH, Glargine, Detemir) — Veterinary Vademecum Drug Reference

Dosage & Administration Guidelines

Species	Route	Dose	Frequency	Duration & Clinical Notes
Dog	SC	0.2-0.5 U/kg initially (NPH or glargine); adjust based on glucose curves	q12h (NPH, glargine, detemir) or q24h (glargine in some cases)	Duration: Lifelong Notes: Start with 0.25 U/kg q12h; adjust by 10-20% every 3-7 days based on serial glucose curves. Regular insulin for DKA: 0.1-0.2 U/kg IV bolus, then 0.1 U/kg/h CRI.
Cat	SC	0.2-0.5 U/kg initially (glargine or detemir); regular for DKA	q12h (glargine, detemir) or q24h (glargine in some cases)	Duration: Lifelong; remission possible Notes: Start with 0.25 U/kg q12h; adjust based on glucose curves. Glargine often preferred for cats. Regular insulin for DKA: 0.05-0.1 U/kg IV bolus, then 0.05-0.1 U/kg/h CRI.
Horse	IV	0.1-0.2 U/kg regular insulin (for hyperlipemia) with glucose infusion	q6-12h or CRI	Duration: Until clinical improvement Notes: Monitor glucose closely; administer with dextrose to prevent hypoglycemia.
Cattle	IV/SC	0.1-0.2 U/kg regular insulin (for ketosis) with glucose	q12h	Duration: 2-3 days Notes: Use with caution; monitor glucose.
Small Ruminants	SC	0.2-0.5 U/kg (if indicated)	q12h	Duration: As needed Notes: Not commonly used; individualize.
Rabbit	SC	0.5-1 U/kg (if indicated)	q12h	Duration: As needed Notes: Limited data; monitor glucose closely.
Bird/Poultry	SC/IM	0.5-2 U/kg (if indicated)	q12-24h	Duration: As needed Notes: Limited data; use with caution.
Exotic/Other	SC	0.2-0.5 U/kg (if indicated)	q12h	Duration: As needed Notes: Individualize based on species and glucose monitoring.

Clinical Indications & Species Uses

General Indications

Management of diabetes mellitus
Treatment of diabetic ketoacidosis
Adjunct in hyperkalemia

Dog (Canine)

Diabetes mellitus (all types)
Diabetic ketoacidosis (regular insulin IV)
Hyperkalemia (regular insulin with dextrose)

Cat (Feline)

Diabetes mellitus (especially type 2, often with remission potential)
Diabetic ketoacidosis (regular insulin IV)

Horse (Equine)

Hyperlipemia in ponies/miniature horses (with glucose)
Diabetes mellitus (rare)

Cattle (Bovine)

Ketosis (with glucose, though less common)
Diabetes mellitus (rare)

Rabbit & Small Mammals

Diabetes mellitus (rare)
Anorexia (as anabolic agent, experimental)

Exotic & Other Species

Diabetes mellitus in ferrets, primates, and other exotic species (rare)

Pharmacology & Mechanism of Action

Drug Class: Antidiabetic agent | Pharmacological Group: Hormone (pancreatic polypeptide)

Mechanism of Action: Insulin is a peptide hormone that binds to specific insulin receptors on target cells (muscle, adipose tissue, liver), activating a tyrosine kinase cascade that promotes glucose uptake, glycogen synthesis, lipogenesis, and protein synthesis, while inhibiting gluconeogenesis, glycogenolysis, and lipolysis. Regular insulin is a short-acting soluble crystalline zinc insulin; NPH is an intermediate-acting insulin with protamine and zinc; glargine and detemir are long-acting analogs with altered absorption profiles (glargine precipitates at neutral pH, detemir is acylated to albumin).

Pharmacodynamics: Insulin lowers blood glucose by facilitating cellular glucose uptake and suppressing hepatic glucose output. It also promotes anabolic effects and inhibits catabolic processes. The onset, peak, and duration of action vary by formulation: regular insulin has a rapid onset (0.5-1 h) and short duration (4-6 h); NPH has a slower onset (1-2 h) and intermediate duration (8-12 h); glargine and detemir have a relatively flat, prolonged duration (up to 24 h) with minimal peak.

⚡ Pharmacokinetics Summary

Absorption: Regular insulin is rapidly absorbed after subcutaneous injection, with peak serum levels in 1-2 hours. NPH is absorbed more slowly due to protamine complex. Glargine forms microprecipitates at injection site, providing slow, sustained release. Detemir binds to albumin, prolonging absorption. Oral absorption is negligible; insulin is degraded in the GI tract.

Distribution: Insulin distributes widely into tissues, but does not cross the blood-brain barrier significantly. It is bound to plasma proteins to a variable extent (detemir >98% bound to albumin; others less). Volume of distribution is approximately 0.1-0.2 L/kg.

Metabolism: Insulin is metabolized primarily in the liver and kidneys by insulin-degrading enzyme (IDE) and other proteases. The liver clears about 50% of insulin on first pass.

Excretion: Renal excretion of intact insulin is minimal; metabolites are excreted in urine. In renal impairment, clearance is reduced.

Half-Life: Regular: 4-6 minutes (IV), but duration of action longer; NPH: 2-4 hours; Glargine: 24 hours (duration); Detemir: 5-7 hours (half-life) but duration up to 24 hours.

Bioavailability: Subcutaneous bioavailability is 50-80% for regular and NPH; glargine and detemir have ~60-80% bioavailability.

Protein Binding: Regular and NPH: low (<10%); Glargine: no significant binding; Detemir: >98% bound to albumin.

Available Formulations & Strengths

Injectable Solution (vials) Regular: 100 U/mL (U-100), also U-500; NPH: 100 U/mL; Glargine: 100 U/mL (Lantus, Basaglar); Detemir: 100 U/mL (Levemir) (SC, IV (regular only))

Prefilled Pens Glargine: 100 U/mL; Detemir: 100 U/mL (SC)

Insulin Syringes U-100 syringes (SC)

Contraindications & Clinical Warnings

Contraindications:

Hypoglycemia
Known hypersensitivity to insulin or any component
Do not use regular insulin IV in formulations containing preservatives (e.g., meta-cresol) unless specified for IV use
Do not mix glargine with other insulins or dilute
Do not use in animals with insulinoma

Warnings & Clinical Precautions:

Use with caution in animals with renal or hepatic impairment
Monitor blood glucose closely during dose adjustments
Do not use in animals with severe hypoglycemia
Avoid abrupt changes in diet or exercise
Insulin requirements may change with stress, infection, or concurrent disease
Use aseptic technique; rotate injection sites
Do not freeze; protect from light
For veterinary use only; keep out of reach of children

Adverse Effects & Reactions

Common:

Hypoglycemia
Local injection site reactions (pain, swelling, redness)
Weight gain
Hypokalemia (with high doses)

Serious / Severe:

Severe hypoglycemia leading to seizures, coma, or death
Hypokalemia
Anaphylaxis (rare)
Insulin resistance (with chronic use)

Rare:

Lipodystrophy at injection site
Allergic reactions
Insulin edema

Key Drug Interactions

Interacting Drug / Class	Clinical Effect & Mechanism	Severity
Beta-blockers (e.g., propranolol)	May mask signs of hypoglycemia and impair glucose recovery	Moderate
Corticosteroids	Increase insulin resistance, may require higher insulin doses	High
Diuretics (e.g., furosemide)	May cause hypokalemia and alter glucose tolerance	Moderate
Glucagon	Antagonizes insulin; used to treat severe hypoglycemia	Moderate
Oral hypoglycemic agents (e.g., glipizide)	Additive hypoglycemic effect	High
Sympathomimetics (e.g., epinephrine)	Increase blood glucose, may reduce insulin effect	Moderate
ACE inhibitors (e.g., enalapril)	May increase insulin sensitivity, risk of hypoglycemia	Moderate

Overdose & Toxicity Management

Signs of Toxicity:

Hypoglycemia (weakness, lethargy, tremors, ataxia, seizures, coma)
Hypokalemia
Adrenergic signs (tachycardia, anxiety)

Emergency Treatment Protocol: For mild hypoglycemia: administer oral glucose (e.g., corn syrup) or feed a meal. For severe hypoglycemia (seizures, coma): administer IV dextrose (0.5-1 g/kg as 25% or 50% solution) slowly, followed by a dextrose infusion if needed. Monitor blood glucose closely. In cases of insulin overdose, provide supportive care, monitor electrolytes (especially potassium), and consider glucagon (0.03 mg/kg IM/IV) if IV access is not available.

Food Animal Withdrawal Times

🥩 Meat: 0 days🥛 Milk: 0 days🥚 Eggs: 0 days

Insulin is a naturally occurring hormone and is generally considered to have zero withdrawal times in food animals. However, extra-label use in food animals requires veterinary oversight and adherence to regulatory guidelines.

Storage, Handling & Regulatory Information

Storage Temperature: Refrigerate at 2-8°C (36-46°F); do not freeze. Vials in use may be stored at room temperature (up to 25°C) for up to 28 days for some products (check label).

Light Sensitivity: Light-sensitive — protect from direct exposure.

Handling & Special Conditions: Protect from light and extreme temperatures. Do not use if frozen or discolored. Keep away from direct heat.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Insulin products are FDA-approved for human use; some are approved for veterinary use (e.g., Vetsulin, a porcine insulin zinc suspension). Other insulins are used extra-label in veterinary medicine.

Extra-Label (Off-Label) Use: In the US, insulin is a prescription drug. Extra-label use in food animals is permitted under AMDUCA with veterinary supervision, but must follow withdrawal times and residue avoidance. For non-food animals, extra-label use is common.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Insulin is the cornerstone of diabetes mellitus management in dogs and cats. Regular insulin is used for rapid control in diabetic ketoacidosis, while NPH, glargine, and detemir are used for maintenance. In cats, glargine and detemir are often preferred due to their longer duration and potential for remission. Dosing must be individualized based on serial blood glucose curves. Owners must be educated on proper storage, administration, and recognition of hypoglycemia. Regular monitoring of fructosamine and clinical signs is essential. In food animals, insulin is rarely used but may be indicated for ketosis or hyperlipemia; withdrawal times are zero but extra-label use requires veterinary oversight.

References & Literature

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