Friday, October 21, 2011

Q & A: Caninsulin Shortage & Insulin Alternatives

I practice in Canada and we have just learned that Intervet's Caninsulin insulin (Porcine insulin 40 IU/ml for those not familiar with it) is on backorder. Our clinic is rather small, and we will likely run short on stock before we will be able to purchase more of the insulin.

Is there suitable insulin alternatives that have been used in the USA (after the withdrawal of Vetsulin)? Any problems or complications that were run into when switching insulin preparations?

My Response:

The only Lente insulin preparation still on the market, at least up until this time, has been Caninsulin (1). This is a 40 U/ml porcine insulin zinc suspension specifically registered for veterinary use and manufactured by Intervet Schering-Plough. Caninsulin is the trade-name for this intermediate-acting insulin preparation (1). It is identical to Vetsulin, the porcine lente insulin that was withdrawn from the US market in early 2010 (2).

On the human market, lente insulin preparations are no longer available. What that means is once your supply of Caninsulin is gone, a totally different insulin preparation will have to be used to control the diabetes. And no, you can't change to a new insulin and administer the same dose that you'd used for the Caninsulin. You will need to again start from scratch to regulate the dog's diabetes with the new insulin preparation.

So what insulin should you switch to? Without porcine lente insulin (Caninsulin or Vetsulin), we have four choices for a insulin substitute in dogs with diabetes.

NPH Insulin
The NPH insulin family is a genetically-engineered version of the human insulin molecule. It is an intermediate acting insulin that uses protamine to delay the absorption of the insulin so that one injection can have a measured effect on blood glucose over 8-12 hours in dogs (3,4). Like lente insulins, NPH is generally given twice a day —an injection with a meal every 12 hours— and provides control of the dog’s blood glucose level for about 8-14 hours.

It is a very popular insulin for treating diabetic dogs, and it has a very good track record of providing good glycemic control, is less expensive than newer insulin analog formulations, and can be purchased without a prescription. At least in the USA, Walmart sells this insulin as ReliOn Humulin N for significantly less than most pharmacies do, only about $25 per vial (5).

NPH/Regular Insulin Mixtures
Humulin 70/30 (Eli Lilly) may be a good choice in dogs previously well controlled on lente insulin. This is a 100 U/ml pre-mixed combination of 30% short-acting (regular insulin) and 70% intermediate-acting insulin (NPH).

Remember that lente insulin (Caninsulin or Vetsulin) is actually a mixture of rapid-acting and long-acting insulins (Semi-lente and Ultralente, respectively) (6,7). Because it has a similar duration/action curve to lente insulin, Humulin 70/30 insulin is well suited to a twice-daily dosing regimen in diabetic dogs where meals are fed at the same time as the insulin injections (8).

Again, Walmart sells this insulin as ReliOn Humulin 70/30 for significantly less than most pharmacies do, only about $25 per vial (5).

Insulin Analogue Mixtures with an Intermediate Duration of Action
Another insulin choice similar to Humulin 70/30, are pre-mixed combinations of a short-acting synthetic insulin analogue (ie, Lispro or Aspart insulin) with a longer-acting insulin analogue (ie. Lispro or Aspart Protamine Insulin) (9).

Examples of these synthetic insulin combinations include Humalog Mix 75/25 (Eli Lilly) or NovoLog Mix 70/30 (Novo Nordisk). Both of these insulin analogue mixtures are given twice daily with meals.

All of these insulin analogue mixtures are 3 to 4 times more costly than human NPH or NPH 70/30 insulins.

Insulin Analogues with a Longer Duration of Action
Finally, my fourth choice is detemir insulin (Levemir, Novo Nordisk). This is another insulin analogue with a long duration of action with a similar action profile to glargine (Lantus), but detemir appears to be more potent and work better in dogs than than glargine does (10,11).

Detemir is the most potent of these insulin choices and is dosed initially at 0.1 U/kg BID, again generally administered at time of feeding. Again, this insulin analogue is 3-4 times more costly than human NPH or NPH 70/30 insulins.

The Bottom Line (for veterinarians in the USA, too)
The fact that Caninsulin is on backorder is worrisome. This sounds very similar to the situation we in the United States had with Vetsulin before it was recalled — and I really doubt if we are every going to get Vetsulin back on the market!

The good news is that we do have alternatives that work in the diabetic dog. We generally start with human NPH insulin, but the NPH-regular insulin mixtures result in better glycemic control in most dogs. And when Humulin 70/30 mixtures fail to regulate the diabetes satisfactorily, we can move on to the newer insulin analogue products.  These include the Humolog or Novolog analogue mixtures, which will be more effective in some dogs, and Levemir (detemir), the most potent insulin preparation that we currently have at our disposal to use in dogs with diabetes.

  1. Caninsulin website.
  2. Vetsulin website.
  3. Goeders LA, Esposito LA, Peterson ME.  Absorption kinetics of regular and isophane (NPH) insulin in the normal dog. Domestic Animal Endocrinology 1987;4:43-50.
  4. Palm CA, Boston RC, Refsal KR, et al. An investigation of the action of Neutral Protamine Hagedorn human analogue insulin in dogs with naturally occurring diabetes mellitus. J Vet Intern Med 2009;23:50-55. 
  5. ReliOn Insulins.
  6. Fleeman LM, Rand JS, Morton JM. Pharmacokinetics and pharmacodynamics of porcine insulin zinc suspension in eight diabetic dogs. Veterinary Record 2009;164:232-237.
  7. Monroe WE, Laxton D, Fallin EA, et al. Efficacy and safety of a purified porcine insulin zinc suspension for managing diabetes mellitus in dogs. Journal of Veterinary Internal Medicine 2005;19:675-82.
  8. Fleeman LM. The recent developments in the management of diabetes mellitus in dogs. 2010 ACVIM Forum Proceedings 2010.
  9. Garber AJ. Premixed insulin analogues for the treatment of diabetes mellitus. Drugs 2006;66:31-49. 
  10. Sako T, Mori A, Lee P, et al. Time-action profiles of insulin detemir in normal and diabetic dogs. Research in Veterinary Science 2011;90:396-403. 
  11. Gilor C, Graves TK. Synthetic insulin analogs and their use in dogs and cats. Veterinary Clinics of North America Small Animal Practice 2010;40:297-307. 

1 comment:

k9diabetes said...

Thank you so much for this article. I run a forum for people caring for diabetic dogs and have seen a lot of confusion in the past two years about alternative insulins for dogs. Many vets were not familiar with NPH, an insulin I really like because it often works very well and is so affordable.

About 90% of the dogs who have come through the forum switched successfully to NPH and a handful have gone to Levemir. The potency of Levemir, though, makes it very difficult to use in small dogs.

We have also seen some creative combinations of NPH and Levemir. One is using Levemir as the primary insulin and adding a small amount of NPH (separate injections) to deal with post-prandial rises in blood sugar. The other uses NPH as the primary insulin and adds a small amount of Levemir to extend the effective duration a full 12 hours.

I worry a great deal about dogs who are either allergic to NPH or do not respond to human insulin. It's a scary time for them.