Selecting the Best Insulin for Diabetic Cats when Cost Becomes Factor

I have an overweight (16 lb; 7.3 kg) male DSH cat who has been fairly well regulated on 3 units of glargine (Lantus) administered twice daily. He has been diabetic for over a year and has done well on a low-carbohydrate diet (less than 10% of calories as carbs).

However, the owner reports that the cost of glargine has risen again (now to just over $200 at our local pharmacy), so the owner wants to switch to another insulin preparation. Glargine has always been my first choice of insulin in diabetic cats so I'm not sure of which insulin would be the best (and cheapest) for this owner to switch to.

Any advice would be greatly appreciated. I'd still like to get this cat to go into remission, but I'm afraid that this will never happen if I stop the Lantus and change to another insulin preparation.

My Response:

The rising cost of all of the human insulin analogs, such as glargine and detemir, are indeed becoming a problem for many owners. If you and the owner decide to switch to another insulin preparation, you have 4 insulin preparations that could be considered (all should be given twice a day):

1. Levemir (insulin detemir), another long-acting human insulin analog
2. ProZinc (Protamine Zinc Insulin; PZI), a long-acting veterinary insulin preparation
3. Humulin N or Novolin N (NPH insulin), an intermediate-acting human insulin preparation
4. Vetsulin (porcine insulin zinc suspension; lente), an intermediate-acting veterinary insulin preparation

Cost comparison
Levemir (detemir): As far as cost, the retail price of Levemir will be about the same or even more than glargine (~$200 per vial), so that's not a good option for this owner.

ProZinc (PZI): A 10-mL vial of ProZinc insulin will be a bit cheaper than either a 10-mL vial of glargine or detemir. Most veterinarians will charge ~$125 - $150 for a vial of ProZinc, whereas both glargine and detemir will be ~$200 or more. That said, ProZinc is certainly not an inexpensive insulin preparation, especially when one considers that ProZinc is a U-40 insulin and each vial contains only 400 units of insulin. Since both glargine and detemir are U-100 insulins, a vial of these insulin preparations will contain 1,000 units of insulin. Therefore, the cost of ProZinc, at least per unit of insulin, turns out to be even more than the human insulin analogs.

Humulin/Novolin-N (NPH): The retail prices of an individual vial of NPH insulin (U-100) will vary widely depending on the pharmacy and its location. At the moment, the least expensive NPH product is Walmart's ReliOn brand (a Novolin insulin), which is sold at ~$25 per vial. However, most other pharmacies charge a retail price of $60 to $100 per vial.  So if you consider the cost per ml of insulin, NPH insulin would be the cheapest.  However, NPH insulin is also the least effective insulin in cats because of its very short duration, so I would not recommend this insulin in any cat, especially if excellent glycemic control or remission is the goal.

Vetsulin (porcine insulin zinc suspension): Vetsulin is available as a 10-mL vial of insulin in a U-40 insulin concentration. For veterinarians, the wholesale cost of the Vetsulin product is inexpensive (~$25 per vial). In most veterinary practices, the retail price of a vial of Vetsulin sold to pet owners will be approximately $50.

Therefore, the cost of a bottle of Vetsulin is similar or even less than the price of NPH insulin and costs much less (about 25-30%) than that of insulin glargine or detemir. But again, the total amount of insulin in a vial of NPH, glargine, and detemir (all U-100 insulins) is 1000 units, where a vial of Vetsulin (a U-40 insulin) contains 400 units, only 40% as much. So in the end, the client cost per unit of Vetsulin would be similar or slightly more than NPH but much less than Lantus, Levemir, or ProZinc.

Effectiveness of insulin preparations in cats
One must remember that it doesn't matter how much money we are saving if the insulin isn't working to control hyperglycemia and prevent ketoacidosis.

Most veterinarians would rank insulin glargine as the first choice of insulin in cats, then insulin detemir or PZI (not the compounded product (1), but FDA-approved ProZinc), then Vetsulin, then finally human NPH insulin as a very last choice (2-10). In my experience, all of the long-acting insulin preparations will show a similar effectiveness and remission rates (~35-50%), although individual cats may respond much better to one of these insulin products.

A number of studies have proven that Vetsulin will certainly control hyperglycemia in cats, especially if combined with a low carbohydrate diet (9,10). The remission rates for Vetsulin, on average, will not be as high as the long-acting insulins, but remission can certainly occur in cats on this insulin.

In this cat, however, remission of the diabetic state is highly unlikely. Most cats will go into remission within 3 months of starting insulin therapy (11-14). If the diabetic state has persisted for longer than 6 months, remission is highly unlikely. This is especially true in diabetic cats like your patient, in which an underlying cause of insulin resistance (i.e., obesity) is present.

Bottom Line

In this cat, given that remission has not occurred after 1-year of therapy with glargine and a low-carbohydrate diet, I would go with the least expensive insulin that will likely be effective in maintaining glycemic control and preventing ketoacidosis.  Overall, the best insulin fitting those criteria would be Vetsulin, which is relatively inexpensive and certainly would be more than adequate in most diabetic cats.

References:

1. Scott-Moncrieff JC, Moore GE, Coe J, et al. Characteristics of commercially manufactured and compounded protamine zinc insulin. J Am Vet Med Assoc 2012;240:600-605.
2. Rand JS. Feline diabetes mellitus In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. Fourth ed. Quedgeley, Gloucester: British Small Animal Veterinary Association, 2012;133-147.
3. Marshall RD, Rand JS, Morton JM. Glargine and protamine zinc insulin have a longer duration of action and result in lower mean daily glucose concentrations than lente insulin in healthy cats. J Vet Pharmacol Ther 2008;31:205-212.
4. Marshall RD, Rand JS, Morton JM. Treatment of newly diagnosed diabetic cats with glargine insulin improves glycaemic control and results in higher probability of remission than protamine zinc and lente insulins. J Feline Med Surg 2009;11:683-691. 
5. Roomp K, Rand J. Intensive blood glucose control is safe and effective in diabetic cats using home monitoring and treatment with glargine. J Feline Med Surg 2009;11:668-682.
6. Roomp K, Rand J. Evaluation of detemir in diabetic cats managed with a protocol for intensive blood glucose control. J Feline Med Surg 2012;14:566-572.
7. Norsworthy G, Lynn R, Cole C. Preliminary study of protamine zinc recombinant insulin for the treatment of diabetes mellitus in cats. Vet Ther 2009;10:24-28. 
8. Nelson RW, Henley K, Cole C. Field safety and efficacy of protamine zinc recombinant human insulin for treatment of diabetes mellitus in cats. J Vet Intern Med 2009;23:787-793. 
9. Martin GJ, Rand JS. Control of diabetes mellitus in cats with porcine insulin zinc suspension. Vet Rec 2007;161:88-94.
10. Michiels L, Reusch CE, Boari A, et al. Treatment of 46 cats with porcine lente insulin—a prospective, multicentre study. J Feline Med Surg 2008;10:439-451.
11. Zini E, Hafner M, Osto M, et al. Predictors of clinical remission in cats with diabetes mellitus. J Vet Intern Med 2010;24:1314-1321. 
12. Reusch CE, Hafner M, Tschuor F, et al. Diabetes remission in cats: a review. Schweiz Arch Tierheilkd 2011;153:495-500.
13. Callegari C, Mercuriali E, Hafner M, et al. Survival time and prognostic factors in cats with newly diagnosed diabetes mellitus: 114 cases (2000-2009). J Am Vet Med Assoc 2013;243:91-95. 
14. Gottlieb S, Rand JS. Remission in cats: including predictors and risk factors. Vet Clin North Am Small Anim Pract 2013;43:245-249.

What's the Best Insulin for Diabetic Cats and Dogs?

With the reintroduction of Vetsulin (porcine insulin zinc suspension) to the U.S. market (1-3), I've received a number of questions concerning the use of this insulin in dogs and cats. Here are the major questions I've received:

• Is this the initial insulin of choice for dogs? 
• How about for cats? Should this be an insulin that we turn to for our newly diagnosed feline diabetics?  
• If we have a dog or cat that isn't responding well to the current insulin, should they be switched to Vetsulin?
• How will this insulin compare to NPH, glargine (Lantus), detemir (Levemir), or PZI (ProZinc) in cats or dogs?  How does the cost compare to these other insulin preparations?

Is this the initial insulin of choice for dogs?
In my opinion, the answer to that is yes, this is the initial insulin of choice for most dogs. Because it's composed of both short and long-acting insulin components, Vetsulin helps control postprandial hyperglycemia and has a longer duration of action than NPH in most dogs (4-7). The cost is approximately the same as NPH, but less than the insulin analogues (e.g., detemir and glargine). See more below, where I do my cost-comparisons for the various insulin preparations.

Is this the initial insulin of choice for cats?
A number of studies have proven that Vetsulin will certainly control hyperglycemia in cats, especially if combined with a low carbohydrate diet (<10% of calories) (8-11). However, the duration of action may be too short in some diabetic cats, and most feel that the longer acting insulin preparations (glargine, detemir or ProZinc) work better to maintain better control of hyperglycemia in cats (11-13).

Of course, maintaining glycemic control throughout the day is more important if diabetic remission is the goal (13,15,16)— if not, Vetsulin might be less expensive and certainly would be more than adequate in most cats (8-10).

If we have a dog or cat that isn't responding well to the current insulin, should they be switched to Vetsulin?
For diabetic dogs not regulated on NPH, the answer is a definite "yes." For cats that are on NPH, Vetsulin would certainly be a better choice, but switching to one of the  longer-acting insulin preparations (insulin glargine, detemir, or PZI) would be a better choice.

How will this insulin compare to NPH, detemir, glargine, or PZI in cats or dogs?  
In dogs, I generally use 3 insulin preparations: Vetsulin, NPH, and insulin detemir. Again, the main problem with NPH insulin in dogs is that the duration of action is too short, and many of these dogs will respond better to Vetsulin. Insulin detemir is the most potent insulin we have for use in dogs, with a longer duration of action (14), but it's much more expensive than either NPH or Vetsulin.

In cats, I never use NPH because of it's short duration, but I will sometimes use Vetsulin as an intermediate-acting insulin.  Most authorities would rank insulin glargine as the first choice of insulin in cats, then insulin detemir or PZI (not the compounded product (17), but FDA-approved ProZinc), then Vetsulin, then finally NPH as a very last choice.

How does the cost of Vetsulin compare to these other insulin preparations?
NPH insulin, insulin glargine, and insulin detemir are all available as 10-mL vials at a U-100 insulin concentration. The retail prices of an individual vial of NPH insulin, insulin glargine, and insulin detemir vary, depending on the pharmacy and its location. I checked out the prices today at my local Walmart, CVS, and Rite Aid pharmacies, and here are the range of prices I was quoted:

• NPH —$24.88 (Walmart's ReliOn brand) to $100.39 (CVS) and $107.99 (Rite Aid)!
• Glargine — $152.84 (Walmart) to $169.99 (CVS) and $188.99 (Rite Aid)
• Detemir — $160.32 (Walmart) to $190.99 (CVS)

Vetsulin (porcine insulin zinc suspension) is available as a 10-mL vial of insulin in a U-40 insulin concentration. The wholesale cost of the updated Vetsulin product is inexpensive ($23.97 per vial), similar to the original product. In most veterinary practices, the retail price of a vial of Vetsulin will be approximately $50.

Therefore, the cost of a bottle of Vetsulin is similar or even less than the price of NPH insulin and costs much less (about 25-30%) than that of insulin glargine or detemir.  But remember, the total amount of insulin in a vial of NPH, glargine, and detemir (all U-100 insulins) is 1000 units, where a vial of Vetsulin (a U-40 insulin) contains 400 units, only 40% as much. So in the end, the cost per unit of most of these insulins preparations woud generally turn out to be similar.

Therefore, the cost of all of these insulin preparations would be similar in most diabetic cats and smaller dogs receiving a typical daily dose of insulin (0.5-0.7 U/kg). Because the concentration of Vetsulin is 40 U/mL, owners of larger diabetic dogs, owner will often go through a bottle within a few days. In these dogs, if insulin resistance is present, it's sometimes cheaper to use a U-100 insulin, such as detemir.

However, the bottom line is clear: it doesn't matter how much money we are saving if the insulin isn't working. Instead, for most pet owners, it's more important use an insulin preparation that best controls the diabetic state. And for most diabetic dogs, that insulin would be Vetsulin, followed by insulin detemir.

References:

1. Peterson ME. Vetsulin Insulin Updated and Approved for Release in USA. Insights into Veterinary Endocrinology. April 17, 2013.
2. Vetsulin website. www.vetsulin.com
3. Vetsulin website: Veterinary Product Updates. www.vetsulin.com/vet/Product_Update.aspx
4. Monroe WE, Laxton D, Fallin EA, et al. Efficacy and safety of a purified porcine insulin zinc suspension for managing diabetes mellitus in dogs. J Vet Intern Med 2005;19:675-682. 
5. Fleeman LM, Rand JS, Morton JM. Pharmacokinetics and pharmacodynamics of porcine insulin zinc suspension in eight diabetic dogs. Vet Rec 2009;164:232-237. 
6. Nelson RW. Canine diabetes mellitus In: Ettinger SJ, Feldman EC, eds. Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat. Seventh Edition ed. St. Louis: Saunders Elsevier, 2010;1449-1474.
7. Davison LJ. Canine diabetes mellitus In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. Fourth ed. Quedgeley, Gloucester: British Small Animal Veterinary Association, 2012;116-132.
8. Martin GJ, Rand JS. Pharmacology of a 40 IU/ml porcine lente insulin preparation in diabetic cats: findings during the first week and after 5 or 9 weeks of therapy. J Feline Med Surg 2001;3:23-30. 
9. Martin GJ, Rand JS. Control of diabetes mellitus in cats with porcine insulin zinc suspension. Vet Rec 2007;161:88-94. 
10. Michiels L, Reusch CE, Boari A, et al. Treatment of 46 cats with porcine lente insulin—a prospective, multicentre study. J Feline Med Surg 2008;10:439-451. 
11. Rand JS. Feline diabetes mellitus In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. Fourth ed. Quedgeley, Gloucester: British Small Animal Veterinary Association, 2012;133-147.
12. Marshall RD, Rand JS, Morton JM. Glargine and protamine zinc insulin have a longer duration of action and result in lower mean daily glucose concentrations than lente insulin in healthy cats. J Vet Pharmacol Ther 2008;31:205-212.
13. Marshall RD, Rand JS, Morton JM. Treatment of newly diagnosed diabetic cats with glargine insulin improves glycaemic control and results in higher probability of remission than protamine zinc and lente insulins. J Feline Med Surg 2009;11:683-691. 
14. Sako T, Mori A, Lee P, et al. Time-action profiles of insulin detemir in normal and diabetic dogs. Res Vet Sci 2011;90:396-403.
15. Roomp K, Rand J. Intensive blood glucose control is safe and effective in diabetic cats using home monitoring and treatment with glargine. J Feline Med Surg 2009;11:668-682.
16. Roomp K, Rand J. Evaluation of detemir in diabetic cats managed with a protocol for intensive blood glucose control. J Feline Med Surg 2012;14:566-572.
17. Scott-Moncrieff JC, Moore GE, Coe J, et al. Characteristics of commercially manufactured and compounded protamine zinc insulin. J Am Vet Med Assoc 2012;240:600-605. 
18. Drugstore.com. www.drugstore.com. (accessed 2006 Oct 3).
19. http://www.relion.com/diabetes/insulin