Know Your Insulin and Dosing Scales

There are many kinds of insulin that are prescribed for our FD cats. Some perform much better than others and each has its idiosyncrasies.

Dr. Hodgkin's Tight Regulation protocol was developed for use with bovine based PZI insulin. Her second choice of insulin, Lantus/Glargine, works very well with TR when cats are first diagnosed FD and have not been on any insulin before. Please scroll down this page for explanations about the different insulin types which will help you chose the right insulin for your circumstances. In the TR College of Knowledge (COK), review the Info sticky for your individual country to determine which insulin is available or may be imported to your country.

Standard recommendation is to do a number of BG testing curves when first starting TR, changing insulin, or when increasing/decreasing doses. The dosing scales provided are a starting point and will likely involve adjustments to the dose amounts as you learn how your cat processes insulin. Please see the Detox Process in the COK for further information about starting TR safely.


PZI – Protamine Zinc Insulin

The PZI we are most familiar with is 100% bovine based PZI which is very gentle insulin, far more predictable than any other for cats, and is the insulin of preference for TR. Bovine based PZI is available in both compounded and manufactured types, and in a variety of strengths from U40 to U100 depending on the source.

The most common PZI types in the US are BCP, VPA – and in Canada, Summit PZI; all are compounded versions of 100% bovine based PZI insulin. Manufactured 100% bovine PZI is also available in the UK under the name Hypurin Bovine Protamine Zinc and can be imported to other countries. ProZinc is manufactured protamine zinc recombinant human insulin. (Because they are no longer available, Idexx PZI Vet and Insuvet are not discussed here. If you can still get these types and want assistance, please post on the Talking TR forum for input.)

Compounded Bovine PZI from BCP, VPA and Summit

BCP and VPA are still compounding PZI and have advised they have a well-stocked supply of bovine pancreatic materials to continue compounding indefinitely. Summit PZI is available in Canada; however the company has had difficulties sourcing pancreatic materials in the past.

Compounded PZI typically comes in 10ml vials, in U40 or U100 strengths and must be prescribed by a vet. Depending on how much insulin your cat needs and how the vial is handled, a vial can last from one to three months or much longer.

When ordering BCP for the first time, there is a free 5ml vial of U100 that is sent to your vet. Most vets, if asked, will pass this free vial along to you for your cat. BCP also sends a number of free "promotional" items to your vet for placing their first order. The coupon for the free vial is on their website - just click on the BCP link above, print out the coupon and give it to your vet.

Hypurin Bovine Protamine Zinc Insulin

Hypurin is a manufactured, U100 Bovine based PZI type made by CP Pharma/Wockhardt in the UK.  We recommend Hypurin as a replacement to Insuvet which has been discontinued.  Depending on where you live, you may be able to import Hypurin to your country – either directly for personal use, or through a government run fee-for-permit or special access program which requires vet participation and can significantly increase costs. The global distributor for Hypurin is MastersDirect. A three month supply of Hypurin can be easily imported to Canada for personal use; to import to the US involves obtaining a special FDA permit. If you are interested in importing Hypurin for your cat, contact the Health branch of your country’s government offices to verify specific requirements. Taxes and duty normally apply when importing insulin for companion animals.

Hypurin is relatively new insulin to DCC and is proving to be very interesting bovine based PZI as it seems to have longer lasting durations, a slower curve, and significant overlap properties. It is available in U100 strength only, and is only one amino acid away from a catís own insulin. The manufacturer recommends that when giving a shot, after pushing the plunger to give the shot not to release the skin right away, leaving the needle in place for 5 seconds before removing the syringe.

ProZinc PZI

ProZinc (protamine zinc recombinant human insulin) was launched in the US in November 2009. It is the only FDA approved insulin for exclusive use in felines. ProZinc is the replacement insulin for Idexx’s PZI vet. ProZinc is U40 in strength.

Most vets in the US will likely prescribe ProZinc as their choice of replacement for Idexx PZI Vet (now discontinued). If your cat is newly diagnosed, and ProZinc will be the first insulin used, we have seen excellent results using ProZinc. But, if your cat has been FD for a while, and has been on other insulin types before, preliminary on-forum data indicates that ProZinc can be difficult insulin to manage. We suspect the reason ProZinc seems to be a challenging insulin when other types have been used before has to do with the combination of it being recombinant human insulin, and its markers being 4 amino acids away from a cat’s own insulin. ProZinc is formulated exactly like its predecessor PZI Vet, with the exception of RHdna replacing the 90% bovine/10% porcine pancreatic materials. ProZinc has a PH of 7.1 to 7.4, and the manufacturer states, since the PH of ProZinc is the same as a healthy cat’s it should be successful insulin for felines. The data from the manufacturer’s clinical trials was collected based on periodic BG testing at Day 7, 30 and 45 – significantly less testing than we do while practicing TR.

Pricing of ProZinc will vary depending on your vet’s mark-up. If you live in the US, Pet Meds will price match as long as you provide a competitor’s website when ordering ProZinc by phone. Please see the US Info sticky for links to price match.

If your cat has been on another form of PZI prior to switching to ProZinc, allow approximately 10 to 12 hours to pass between doses of the two different PZI insulin types. If your cat has been on long lasting insulin such as Lantus or Levemir, allow approximately 18 to 24 hours to pass before starting ProZinc. For medium acting insulin types such as Vetsulin/Caninsulin and/or NPH, a minimum of 10 to 12 hours to pass before starting ProZinc is recommended.

Starting PZI Treatment

Ideally you should start any insulin when you are available to monitor your cat’s BG frequently by performing curves for a few days until you know how your cat processes their insulin.

U100 strength PZI must be used with U100 syringes. When using U40 strength PZI, you have the option to use either U40 syringes, available only from your vet, or to use U100 syringes (3/10cc with half unit markings).Purchasing U40 syringes from your vet is very expensive (prices range from $25 to $40 per box of 100-U40 syringes). A box containing 100 syringes with half unit marks for use with U100 insulin can be purchased for as little as $12.50 at Wal-Mart. The second advantage to using U100 syringes with U40 PZI is the ability to more accurately measure doses in as little as 0.2u increments. This is very handy should your cat be sensitive to insulin and need only slight increases/decreases to dosage.

 

Please be aware that there are several sizes of U100 needles, each holds different amounts of fluid - 3/10cc/ml, 1/2cc/ml and 1cc/ml. The 3/10cc and the 1/2cc both have draw lines on the barrel that equal one unit, while each of the draw lines on the 1cc syringe equals two units. It is important NOT to buy the 1cc syringes, as the 2u draw lines can make it very easy to overdose! Buy only 3/10cc syringes with half unit markings!

 

When using U40 insulin with U100 syringes, you MUST use a conversion chart to factor for the difference in volume between U100 and U40 strengths. You can find the conversion chart here. Briefly, U100 insulin is 100% insulin – U40 insulin is 40% insulin with 60% suspension added (typically saline). In order to make up for the difference in the percentage of insulin between the two strengths when using U100 syringes, the U40 insulin must be multiplied by 2.5 – for example, if you need 1.0u of U40 insulin and you are using a U40 syringe, you simply draw to the 1.0u line on the syringe. However, when using U40 insulin with U100 syringes, to get the same 1.0u of insulin, you need to draw the insulin to the 2.5 unit line on the U100 syringe. It is the same amount of insulin, just a different volume depending on which syringe is used. This is a little baffling at the beginning of TR but, as long as you are using the conversion chart, make sure to put old U40 syringes far out of reach, and remember that there are two steps to loading the syringe –identifying the amount of the dose, then making sure you convert for the DRAW on the syringe, it is safe to use U100 syringes.

More so than other insulin types, PZI is very fragile. Practicing TR we typically handle our insulin more often than twice a day. It is very important to keep movement of the insulin to a minimum. Vials should be turned end over end very gently, only two or three times before drawing your dose. The vial should not be rolled between warm hands, or shaken, regardless of what the manufacturer’s instructions state. An interesting discovery made on forum is that should a vial begin to lose potency, PZI insulin types seem to revitalize if left to "rest" in the fridge for a week or two.

PZI should be stored in the fridge at all times, in a protected spot on a less used shelf, in a sturdy container where it will not get knocked over. Do not store insulin on the door of your fridge to avoid excess jostling. When preparing to draw a dose of PZI, pull the plunger back on the syringe a unit or two more than the desired dose before inserting the syringe into the vial. With the vial upright, stick the syringe into the vial and slowly express the air in the syringe into the vial to create a vacuum. Once the syringe is empty of air, then gently turn the vial upside down and draw insulin into the syringe, just past the desired dose. With the vial still upside down, slowly expel the extra insulin back into the vial, then remove the syringe from the vial.

PZI is long lasting insulin generally remaining in the system for approximately 12 hours per shot. When first starting TR, onset usually occurs between +2 and +3 hours after shot; nadir is typically from +4 to +6 hours after shot, and by +8 hours after shot, the insulin begins to leave the system. These time lines are the norm and are likely to change as your cat begins to heal: EDID - every cat is different.

It is very important to maintain overlap with PZI– meaning that the remnants of the prior shot are still working to keep the BG as close to normal range as possible, while the next shot approaches onset. PZI is insulin that can be dosed as early as +6 hours after the last shot when the rise in BG has been confirmed. In fact, at the start of TR, we recommend you try as much as you can to dose every +6 hours with a BG confirmed to be rising over 150/8.3, to get the overlap working for you as soon as possible.

With PZI we are able to react much quicker to less than satisfactory results. If after two or three shots to scale, you are not seeing BG in the ideal range at nadir, doses can be increased. Experienced members will help you adjust your scale to get your cat into optimal normal range numbers as quickly as possible.

Recommended Starting Scale for PZI (after 12- 24 Hour Detox)

BG

US(mg/dl) Metric(mmol/L)   Dose

151-170         8.3-9.4             0.25u

171-185         9.5-10.2            0.50u

186-200        10.3-11.1           0.75u

201-220        11.2-12.2           1.00u

221-250          12.3-13.8          1.25u

251-290          13.9-16.1          1.50u

291-350          16.2-19.4          1.75u

351-410          19.5-22.7          2.00u

411-450          22.8-25.0          2.25u

451-500          25.1-27.8          2.50u

 

Lantus (aka Glargine)

Alert about Lantus issued by FDA

Lantus/Glargine is human insulin that comes in U100 strength and requires the use of U100 syringes. It is sold in either 10ml vials, or 3ml cartridges (in 5 packs) that are designed for use with injection pens that are purchased separately. We recommend purchasing Lantus cartridges, but do not recommend buying the injection pens as it is impossible to measure part unit doses. Lantus cartridges look very much like "mini" vials, with a rubber stopper at the top. Purchasing cartridges will be more expensive at the outset (about $25-$30 more than a 10ml vial of Lantus) but there is much less waste compared to purchasing 10ml vials. Lantus expires approximately 28 days after opening, so it's likely that even a 3ml vial would not be empty by the time Lantus loses its potency. We recommend storing Lantus in the fridge. Depending on how it has been handled, we have found that Lantus can remain potent well past 28 days.

Lantus is clear, just like water. Should you ever see any crystals in the vial or cartridge, the Lantus has been damaged and should be discarded. If bubbles appear in Lantus, it will start to lose potency. Unlike when filling a syringe with PZI, it is recommended not to draw air into the syringe to express into the vial when measuring a Lantus dose, nor to back the insulin out of the syringe while it is still in the vial in an effort to avoid creating air bubbles. Draw more than your required Lantus dose into the syringe by at least a unit, remove the syringe from the vial and express the extra insulin onto a paper towel or tissue to avoid creating bubbles.

Lantus is available at any drug store as it is commonly used in humans. In some countries, like Canada for example, Lantus is available over the counter and does not require a prescription. If you are purchasing Lantus through your vet, you may wish to check pricing with your local pharmacy first in order to save yourself the extra cost of vet mark-up. Prices differ greatly – for example, premier drug stores charge $30 to $40 dollars more, where well-known stores such as Wal-Mart and Costco charge a lot less for Lantus.

When giving insulin shots, particularly with Lantus, you want to slowly push the plunger of the syringe in completely and with the syringe still inserted under the skin, slowly count to 10 before removing the needle from the injection site. You may have to hold your cat gently while you wait. Remove the syringe and very gently apply pressure for several seconds. DO NOT RUB THE AREA to avoid damage to the Lantus molecules.

Lantus is long lasting insulin, remaining in the system for 12 hours or more. It typically drops the BG slowly, has an extended nadir, and begins to slowly leave the system after approximately 8 to 10 hours. These are the norm, every cat is different. It is very important to maintain overlap on Lantus – meaning that the remnants of the prior shot are still working to keep the BG as close to normal range as possible, while the next shot is coming to onset.

Lantus is insulin that cannot be dosed any sooner than +10 hours after the last shot, and only to a rising BG over 150/8.3. It is imperative that your cat is curved on the first three or four shots when starting out, or when making even very minor dosing changes. The first curve starts with the test before shot, continues with testing every two hours afterwards to determine onset, nadir (peak insulin activity) and when the insulin starts to leave the system. The timing for tests on the second curve is dependent on the first curve’s results.

When using Lantus, rather than starting with a static dose every 12 hours as is typically prescribed, TR requires the use of a three rung sliding scale, with dosing at approximately every 10 hours as determined by the cat’s progress. When compared to PZI, a tighter dosing scale is used with Lantus and we find that the scale becomes almost "static" over time, with only very small adjustments made to doses. Eventually the Lantus scale is reduced to two rungs, and then possibly to one rung as the cat becomes better regulated.

Unfortunately there is a big challenge to using Lantus. It is released over time and does not result in the instant gratification that is seen with all of the other insulin types. In humans, Lantus crystals are still present in the system 24 to 48 hours after dose. In cats, due to their much faster metabolisms, Lantus lasts approximately half that time.

It takes approximately two, if not three shots of Lantus before you know if the dose is doing what it is supposed to do, such as reaching ideal numbers at nadir. If ideal BG is not reached after two to three doses, increases should be made by either "fat" increases or a maximum increase of 0.25u increments only.

Using Lantus requires PATIENCE.

Recommended Starting Scale for Lantus (after 24 Hour Detox)>

BG

US ( mg/dl)   Metric (mmol/L)      Dose

150 - 250         8.3 - 13.9            0.25u

251 - 400         14.0 - 22.0          0.5u

400 +                 22.2 +              0.75u

Levemir/Detemir

Levemir is another new to the market, synthetic human insulin which is now being used on felines. It works very similarly to Lantus. Those wanting to practice TR using Levemir/Detemir are recommended to follow the instructions and dosing scale for Lantus as posted above. Unlike Lantus, Levemir can be dosed as early as every 8 hours which works better for some cats.  Experienced members on forum can assist to determine if earlier dosing will work better for your cat.  It is reported many cats that have not been well regulated on Lantus or other insulin types can become better regulated when switched to Levemir.

 

Vetsulin (aka Caninsulin)

Alert about Vetsulin/Caninsulin Issued by the FDA

Vetsulin is also known as Caninsulin. The FDA recently approved the use of Vetsulin for cats. But that does not change the fact that it is insulin created for dogs, hence the name Canin-sul-in. In fact, Intervet’s own documentation states that the clinical trials of Vetsulin on cats lasted a total of 180 days – that’s only 6 months to determine the safety of a very powerful hormone on a very sensitive species!

Vetsulin is a porcine insulin zinc suspension (PIZ), at least 3-4 amino acids away from a cat's own insulin. It is U40 in strength and requires the use of U40 syringes only. It is available in both 10ml and 2.5ml vials. Because of labeling on the box (PIZ versus PZI), there are reports that some vets have confused an owner’s request for PZI to be a request for Vetsulin. It is uniformly cloudy or milky. It should be stored in the fridge in an upright position to avoid crystals forming around the stopper.

Vetsulin is intermediate acting insulin, meaning that onset usually occurs between +1 and +2 hours after dose; nadir is approximately +4 to +6 hours after dose and it usually has left the system by +8 hours after dose. These are the norm, every cat is different.

Our experience working with owners using Vetsulin is that it drops the BG very fast, nadir is relatively short lived, and it leaves the system very quickly resulting in what we can only call a "roller coaster" as far as BG curves are concerned.

Vetsulin can be dosed as soon as +6 hours after the last shot, once a rising BG over 150/8.3 is confirmed. Intervet’s Vetsulin dosing and administration guidelines state that blood glucose values will range between 120-350 mg/dl in what they consider well-regulated diabetic cats, far above the recommended BG we expect to see at nadir on TR.

While cats to achieve diabetic remission using it, Vetsulin/Caninsulin is not the best insulin for cats.

Recommended Starting Scale for Vetsulin (aka Caninsulin) (after 24 Hour Detox)

BG

US(mg/dl)   Metric(mmol/L)   Dose

151-170           8.3- 9.4           0.25u

171-185           9.5-10.2           0.50u

186-200          10.3-11.1          0.75u

201-250          11.2-13.8          1.0u

251-350          13.9-19.4          1.25u

351-410          19.5-22.7          1.5u

 

 

NPH (Humulin N) Insulin

NPH (Neutral Protamine Hagedorn) is human recombinant insulin, which comes inU100 strength and must be used with U100 syringes. It is very similar to natural canine insulin and is commonly used for dogs. NPH should appear cloudy in the vial. It is one of the cheapest insulin types on the market, and can be left at room temperature for up to 28 days, although refrigeration will increase length of potency. It is stable insulin in that it is not quite as sensitive to knocks and drops as the others. It should not be used after the expiration date. There should be no clumps or white particles in the suspension. If clumps or spots appear, turn the vial end over end a number of times to see if the clumps or spots dissipate. If they do not, the insulin is damaged and should not be used.

It is approximately 3 to 4 amino acids away from a cat’s own insulin. It is highly recommended to do 1-hour curves when using NPH, starting at +1 after shot until the insulin starts to leave the system. Onset for NPH occurs between +1 and +2 hours after shot, nadir is approximately +2 to +4 hours after shot, and it leaves the system usually by +6 hours after shot. These are the norm, every cat is different. NPH is the only insulin that can be dosed earlier than +6 hours after shot to a rising BG in special circumstances only. Experienced members will help you decide what approach to take with NPH. Even more so than Vetsulin/Caninsulin, NPH drops the BG fast, has a very short nadir and leaves the system very quickly. It is not abnormal to see drops from a BG in the 400’s(20.0’s) to the 40’s (2.0’s) and back up to the 400’s (20.0’s) within a six to eight hour period.

NPH is not the best choice for cats. That said, it is an acceptable "in a pinch" insulin for times when for example, you’ve dropped and shattered your vet-prescribed insulin vial on the floor, the vet clinic is closed for a couple of days, and the drug store is still open. Please ask for assistance should you need to switch to NPH in an "urgent" situation.

Recommended Starting Scale for NPH (after 24 Hour Detox)

BG

US(mg/dl)  Metric(mmol/L)    Dose

151-170           8.3- 9.4           0.25u

171-185           9.5-10.2           0.50u

186-200          10.3-11.1          0.75u

201-250          11.2-13.8          1.0u

251-350          13.9-19.4          1.25u

351-410          19.5-22.7          1.5u

 

Fast Acting Insulin Types

There are a number of fast acting insulin types that may be of assistance for very hard to control cats. One of these is known as "R". Most cats on TR do not require fast acting insulin and therefore, we do not provide standard dosing recommendations for these. If you find yourself in the situation where fast acting insulin is required, please post on Talking TR asking for case-by-case assistance from another member well experienced with fast acting insulin, and, you should always confer with your vet on how they are used.

 

If you have any questions about any of the information provided in the Insulin and Starting Scales sticky, please post your questions on the Talking TR forum.

 

Updated March 2011