405 Heron Drive Suite 200
Swedesboro, NJ 08085
Ph 800.331.8272

Protamine Zinc Insulin for Veterinary Use

by Barbara Forney, VMD

Basic Information

Protamine zinc insulin (PZI) is a long-acting insulin combination. Protamine zinc is added to insulin as a means of slowing insulin absorption. PZI once was made with beef and pork insulin but the PZI described in this monograph is made with human recombinant insulin.

Dogs and Cats

Diabetes mellitus is a relatively common metabolic disease seen in middle-aged cats and dogs. Most dogs suffer from Type 1 diabetes, while cats usually have Type 2 diabetes. Type 3 diabetes may occur in either cats or dogs.

In addition to insulin, the veterinary management of diabetes requires owner education, dietary management, and regular glucose testing. With appropriate management, most animals can live a normal-duration life. Human recombinant insulin found in PZI is acceptable for use in dogs and most cats.

When administered subcutaneously, the onset of action is between one and four hours; the peak is between four and eight hours; the duration of action is from six to 24 hours in the cat and six to 28 hours in the dog.

PZI generally is given once a day. There are oral hypoglycemic drugs that may be used in addition to or in place of insulin in some cats.

Protamine Zinc Insulin Side Effects

Hypoglycemia: The initial signs of hypoglycemia include nervousness, vocalization, anxiety, muscle tremors, ataxia, and pupillary dilation. The alert owner may be able to offer the patient some food or oral dextrose to counteract the hypoglycemia. Positive response should occur within one or two minutes. More severe signs of hypoglycemia include seizures, shock, and coma. These animals require prompt veterinary intervention.


  • Urinary tract infections are a common secondary problem in cats with diabetes.
  • Intact female cats should be neutered because the increased progesterone with diestrus makes managing of diabetes more difficult.
  • Dietary changes can affect insulin requirements.
  • Insulin may be used in pregnant animals although breeding animals with diabetes generally is discouraged. Insulin may be used in lactating animals.
  • Injection site reactions may occur. It is important to use multiple sites.

Drug Interactions

  • There are multiple drug-interactions with insulin.
  • Drugs that may increase the hypoglycemic activity of insulin include Captopril, Enalpril, alcohol, anabolic steroids, beta-adrenergic blockers, MAOI's, Guanethidine, Phenylbutazone, Sulfinpyrazone, Sulfonamides, Tetracycline, and Aspirin or other Salicylates.
  • Drugs that may decrease the hypoglycemic activity of insulin include Dextrothyroxine, Dobutamine, Epinephrine, Estrogen/Progesterone combinations, Furosemide, Glucocorticoids, Isoniazide, Phenothiazine derivatives, and Thiazide diuretics.
  • Thyroid hormones may increase blood glucose levels. When thyroid hormone is begun in a diabetic, hypothyroid patient, additional monitoring should be considered.
  • Topical glucocorticoids can alter glucose levels in the diabetic patient and should be avoided if possible.
  • Insulin can change serum potassium levels. Patients receiving digoxin and those on diuretics should receive additional monitoring of serum potassium levels.


Overdose with insulin will lead to varying degrees of hypoglycemia. Description of mild hypoglycemia is included with the side effects. More severe hypoglycemia can lead to seizures, blindness, cerebral edema, permanent brain damage, coma, and death.

For Veterinary Practices
For Pet & Horse Owners


Therapeutic Class
Pancreatic Hormone

Dogs and cats

May Be Prescribed by Vets for:
Diabetes mellitus

Search for Available Dosage Forms

About the Author

Dr. Barbara Forney

Barbara Forney, VMD

Dr. Barbara Forney is a veterinary practitioner in Chester County, Pennsylvania. She has a master's degree in animal science from the University of Delaware and graduated from the University of Pennsylvania School of Veterinary Medicine in 1982.

She began to develop her interest in client education and medical writing in 1997. Recent publications include portions of The Pill Book Guide to Medication for Your Dog and Cat, and most recently Understanding Equine Medications published by the Bloodhorse.

Dr. Forney is an FEI veterinarian and an active member of the AAEP, AVMA, and AMWA.