Pet Health: PZI (Protamine Zinc Insulin)

What is PZI?
Why use PZI?
What do the strength numbers (U40, U100) mean?
What about shelf life?
Which PZI should I get?
PZI source list

What is PZI?

PZI (Protamine Zinc Insulin) is a type of insulin combined with zinc and protamine (a protein extracted from salmon) to slow the release of the insulin into bodily tissue. It works well in controlling diabetes in many cats. PZI insulin production has undergone many changes in the last 5 years and is now generally a veterinary only insulin so you won't be able to buy it at a human pharmacy. If you chose to use PZI, it may only be available in U-40 strength (as opposed to the more common U-100 strength) and will require special syringes or use of a conversion chart if you only have U-100 syringes.

ProZinc®is the first and only FDA-approved insulin for cats made from recombinant DNA (DNA molecules created from the DNA of two unrelated organisms) that is identical to human insulin. The ingredients in ProZinc ®(protamine zinc insulin) are classified as long-acting with duration of effect for 10-14 hours.

A number of veterinary pharmacies compound PZI, usually from 100% bovine insulin. Bovine insulin is a much better match for feline insulin than is human insulin and therefore works better in cats.

Why use PZI?

Human insulin, in general, does not successfully replace the cat's own insulin, and diabetes is not well-controlled in most cats when human (e.g. Humulin) insulin is used for treatment. Bovine (beef) insulin is most similar in molecular structure to feline insulin, and it is thought for this reason, to be most effective for these cats.

Although PZI is not generally considered the first choice for treatment of feline diabetes, many cats do well on PZI insulins. A scientific study has shown that 75% of previously treated hard-to-regulate cats were better controlled on PZI.[1] The study's author stated that most cats require PZI injections twice daily. Also, absorption, peak and duration of PZI is variable.

What about shelf life?

    Factors affecting shelf life of a vial that has been opened are:
  • exposure to light
  • accumulating contaminants from re-used syringes (or even new syringes)
  • mixing with incompatible
  • lack of refrigeration (loss of sterility)
  • chemical instability

Home testing will enable you to determine for yourself whether the insulin is maintaining its effectiveness. You should not use insulin that suddenly looks different. PZI is clear (not cloudy) with white sediment (no clumps), that when mixed gently, looks like watery milk. Compounded insulins, as well as user-diluted or mixed insulins have an opened-life of 30 to 90 days with reasonable care.

Which PZI should I get?

It is impossible to predict which insulin will work best for your particular cat. Two diabetic cats in the same household (i.e. same diet and schedule) can respond differently to the same insulin.

If your cat doesn't respond even to large doses of human insulin, meaning that blood sugar consistently stays very high despite doses larger than 1 unit per pound, and assuming there is not another serious problem causing the high blood sugars, it makes good sense to try the compounded bovine PZI or the recombinant DNA ProZinc ®.

If your cat responds to human insulin, but bg's (blood glucose values) cannot be maintained within the ideal range of 100-300mg/dl (5.5 - 16.7 mm/ol), by all means consider PZI (either animal or human), but first, review the "lifestyle" suggestions below.

Lifestyles of the diabetic cat

Most people with a newly diagnosed diabetic cat start treatment with human insulins, injected twice a day, since they are widely available, relatively inexpensive, and will work well for many cats. If you're inexperienced (and/or have an inexperienced vet), and the insulin you're using "doesn't work", realize that the insulin is only about half the treatment. There's a great deal that you can learn to do to help the insulin (whatever it is) work longer and better. Even if you've been around the block a few times, if you’re having difficulties, these points are worth reviewing.

Many people turn to PZI because their cat exhibits wide swings in blood sugar levels, from 400+ (or more) to sub-100's, but with extremely variable (unpredictable) readings at all points on the curve. Very often, this is due to giving too much insulin without sufficient testing to see the whole cycle.  If this is the case, cutting the dose in half (or more) for several days and more frequent testing will result in a flatter curve AND lower average numbers. Excessive doses of insulin can mean steep roller coaster curves, with peak readings (the insulin's strength is at its peak, and blood sugar is lowest) that vary from being dangerously low, to being higher than desirable.  Large doses affect the insulin's duration as well, and may cause excessive overlapping of the next dose (a sign of this is a dinner bg reading much lower than the breakfast reading).  If doses are overlapping, changing doses "on the fly" is inadvisable because the effect of the overlap on the next dose will always vary.  It is most important where overlap is suspected to find a minimal dose that can be given consistently.

Insulin acts to push blood sugar levels down, diet is a major factor in what pushes blood sugars up. We try to balance the effect of the insulin with the appropriate diet and feeding schedule to obtain a flat curve in the target range (300 to 100mg/dl). With PZI, as with any long-acting insulin, the role of diet cannot be overstated. It is almost impossible to manage a large post-meal surge in blood sugar with a long acting insulin such as PZI (or Ultralente), due to its slow onset, and weak action. Trying to do so usually means excessively large doses, steep curves and widely variable readings at shot time.  You can help a weak-acting insulin to control blood sugar by making dietary changes, and you'll get flatter curves and lower numbers overall. To avoid post-meal surges, make sure the diet (even if recommended by your old-school vet) is low in CARBOHYDRATES. Dry cereals (especially diets created for weight-loss) always have significantly more carbohydrates than wet food. When switched to an improved, carbohydrate-restricted, high protein diet, some cats produce enough insulin themselves and no longer need injected insulin. Cats are carnivores, and require no more than 6% carbohydrate (cereals contain as much as 30 or 40%). Purina has done case studies (soon to be made public, 1-800-222-8387 for more info) in which they observed that 93% of cats lower or eliminate insulin requirements when fed their new canned food called Purina CNM DM-Formula (prescription only).  It is high in fiber and protein, low in carbohydrates.  If you're unable to halt the post-meal surges without large doses, even with a corrected diet, consider trying a combination of a long-acting insulin at 12-hour intervals to provide "fasting" coverage, augmented at mealtimes with a fast-acting, short-duration insulin (use 2 syringes unless you know they're compatible. Usually only a fractional unit of the fast-acting insulin is needed, so you can dilute it.) Caution: substantially reducing carbohydrates in the diet is a POTENT factor in reducing blood sugars and altering bg curves, and it should not be done without also reducing insulin, and careful monitoring.

To get consistent curves, the diet must also be consistent. Caloric intake and schedule should be the same, day to day. If replacing dry food with canned food or "people food", be careful to replace the calories as well; dry foods have 3 or 4 times the calories, by weight. More calories require more insulin, fewer calories require less. Other sources of inconsistency: free feeding in a multi-cat household is not desirable. Canned foods may vary quite a bit in carbs and calories, depending on the "flavor". Detailed nutritional information can be obtained by calling the phone number listed on the can or bag. Be sure to compare equal caloric amounts.

Increasing soluble fiber (metamucil, psillium husks) is thought to slow and even out the process of digestion which may flatten out the insulin's peak (the lowest point on the bg curve) as well as moderate the post-meal rise in blood sugar. Be sure to monitor carefully when adding fiber.

Just enough duration from the previous dose to overlap the new dose while it's gaining strength is desirable. Too much overlap will (sooner or later) drop blood sugar too much. You’re aiming for 12-hour blood sugar values within around 10% of each other.  Remember that even before you’ve achieved regulation, you want a gentle curve that gradually gets lower overall as dosage increases.   A steep drop from a very high reading, to a good peak cannot achieve regulation in the end.  12-hour readings should be close enough to each other that dosage can remain consistent.  If the 12-hour reading is so much lower that you cannot repeat the same dose consistently (assuming that the peak will also be a lot lower), you will have a roller-coaster situation where the affect of duration will always vary.  The difference between doses that are "too much" and "too little" can be minute -- as little as a quarter-unit. If your cat is very sensitive to small increments, consider the more dilute PZI from IDEXX (U40 strength) and use a U100 syringe if necessary (see "Strength" discussion below). Unlike other insulin, diluting PZI yourself, is not recommended.

Make sure that you're keeping a consistent injection schedule, so that blood sugars don't get out of control due to an injection given too late, and don't plummet because the injection is given too early. What is "too late" and "too early" will depend on the insulin's duration for your cat.

For various reasons, insulin may be absorbed erratically, and this may affect large doses more than small ones. Avoid using the scruff of the neck for injections, as there is insufficient blood supply to that area. Rotate the injection site to avoid building scar tissue and consequent absorption problems.

Certain conditions render bodily tissue insensitive to insulin, this is called insulin resistance. Obesity is a major cause of insulin resistance. One of the most effective (and most challenging) ways for a fat cat to lower bg levels, and possibly eliminate the need for injected insulin altogether, is by losing excess weight. Exercise, smaller portions of a carb-restricted diet, reduced fat, or restriction or elimination of treats are ways to accomplish weight loss. Note that dry foods sold as low calorie, high fiber, for “Seniors” or weight-loss may be higher in carbohydrates, lower in protein than normal dry food (which is already higher in carbs than wet food), and should not be given to diabetics.  Something is wrong if your cat appears to be "starving" -- he or she may have very high, or very low blood sugar at that time -- it is not necessary or desirable to starve your cat. High blood sugar alone is a major cause of insulin resistance -- you will notice that the same dose will have more impact when given at lower bg levels than at high levels.

Other causes for consistently high blood glucose values are, pregnancy, stress, certain medications (corticosteroids), infection (diabetics are especially susceptible to urinary infections) and disease (renal, hyperthyroidism, liver disease and cancer to name a few). These possibilities should be ruled out.

How Much Insulin is Too Much?

The Cornell University Feline Health Center has addressed the topic of high insulin doses in cats. Excessively high insulin doses are those greater than one to two units of insulin per pound per day. Felines who use more insulin than this should be evaluated more intensively. Other diseases may be underlying or complicating the diabetes mellitus and as a result, necessitate high insulin dosages. Problems with insulin injection, poor absorption or too rapid metabolism of insulin, or even insulin overdose are potential causes of an apparently excessive insulin requirement.


[1] Richard W. Nelson, DVM, DACVIM et al; Efficacy of protamine zinc insulin for treatment of diabetes mellitus in cats; 2001

Last updated November 2011
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