Insulin Glargine and Injection Pain in Cats

I have a 10-year-old neutered male diabetic cat that has been on 3 units of insulin glargine (Lantus) twice a day for 3 months. The cat's diabetes has responded very well. Over the past few days, however, the owner says that the cat has been in severe pain and appears to be very sensitive in the back area where the insulin injections are given.

The owner did her own research on-line and found information to suggest that Lantus can cause "shooting pain" in some human diabetics. Could this truely be a cause for the cat's pain, or are we most likely dealing with a hyperesthetic syndrome or an orthopedic problem?

They can not bring the cat to me for an exam for a couple of days. Do you have any other suggestions for insulin therapy if the owner decides that they want to stop the Lantus injections?

My Response:

In man, pain resulting from the injection of insulin glargine (Lantus) certainly can occur (1-3). In clinical studies of adult patients done by the manufacturer of Lantus, there was a higher incidence of treatment-emergent injection site pain in glargine-treated patients (2.7%) compared to NPH insulin-treated patients (0.7%) (1).

The reason for the higher frequency of injection pain appears to be related to the fact that, unlike other insulins, insulin glargine is injected as an acidic solution with a pH of 4 (1-4). Careful investigation in children confirm that some individuals will indeed perceive more pain during subcutaneous injection of acidic insulin solutions than neutral insulin solutions (3).

If you decide that a change in insulin preparation is indicated in this cat, alternative, nonacidic, long-acting insulin options for cats include PZI (ProZinc) insulin and insulin detemir (Levemir) (4-9). Lente or NPH are also nonacidic insulins; however, both are intermediate-acting insulin preparations and may have a duration of action that is too short for the diabetic cat (10).

That all said, the pain you describe sounds like the cat's pain is constant and may not be related to the insulin or insulin injections at all. Again, this cat needs a good old physical examination to help sort out the underlying cause of the pain that the owner is describing.

References:

1. Hirsch IB. Insulin analogues. N Engl J Med 2005;352:174-83.
2. LANTUS (insulin glargine injection), Sanofi-Aventis, Full prescribing information at http://products.sanofi.us/lantus/lantus.pdf
3. Karges B, Muche R, Riegger I, et al. Injection of acidic or neutral insulin and pain: a single-center, prospective, controlled, noninterventional study in pediatric patients with type 1 diabetes mellitus. Clin Ther 2006;28:2094-2101. 
4. Gilor C, Graves TK. Synthetic insulin analogs and their use in dogs and cats. Vet Clin North Am Small Anim Pract 2010;40:297-307. 
5. Nelson RW, Lynn RC, Wagner-Mann CC, et al. Efficacy of protamine zinc insulin for treatment of diabetes mellitus in cats. J Am Vet Med Assoc 2001;218:38-42. 
6. 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. 
7. 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. 
8. Gilor C, Ridge TK, Attermeier KJ, et al. Pharmacodynamics of insulin detemir and insulin glargine assessed by an isoglycemic clamp method in healthy cats. J Vet Intern Med 2010;24:870-874. 
9. 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.
10. 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.