Thursday, May 3, 2012

Treating Diabetic Dogs with Insulin Glargine


PAPER REVIEW

Use of Insulin Glargine in Dogs with Diabetes Mellitus

by F. Fracassi, F.S. Boretti, N.S. Sieber-Ruckstuhl, and C.E. Reusch
Veterinary Record 2012; 170, 52.

Background
Diabetes mellitus is a common disease in dogs requiring insulin  therapy in order to maintain glycemic control. Insulin glargine (Lantus) is a synthetic, long-acting analogue of human insulin that has been designed for once-daily use in human beings (1).

Insulin glargine has been shown to provide effective glycemic control in cats with diabetes (2-4), and in one report, the remission rate of the disease was higher with insulin glargine than with other types of insulin (3). 

Information on the use of insulin glargine for the treatment of diabetes in dogs is scarce and, except for one study that investigated its pharmacokinetics and pharmacodynamics in experimental animals (5), no clinical studies on its use have been published. Therefore, the objective of the study by Fracassi et al (6) was to prospectively evaluate the safety and efficacy of insulin glargine therapy in dogs with naturally occurring diabetes mellitus.

Objectives
The objective of this study was to evaluate the safety and efficacy of insulin glargine in dogs with diabetes mellitus.


Methods
Twelve client-owned dogs with diabetes mellitus were studied (8 females and 4 males). All dogs received insulin glargine every 12 hours for at least six months.The starting dose was 0.25-0.5 U/kg, SC, every 12 hours. Re-evaluations were performed after 1, 2, 4, 8, 12 and 24 weeks and included clinical signs, blood glucose curves, and measurement of serum fructosamine concentrations.

Results
The median starting insulin dose was 0.27 U/kg, BID (range, 0.18-0.53) and increased significantly to a median of 0.60 U/kg (range, 0.11-1.07) after 24 weeks of therapy. Mean blood glucose concentrations were significantly lower after 2 weeks of glargine treatment and remained significantly lower for the duration of the study. Serum fructosamine concentrations were found to be significantly lower after 8 and 24 weeks of insulin glargine therapy compared with the concentrations before treatment.

The number of hours after insulin injection at which the glucose nadir occurred varied between the blood glucose curve, ranging from zero to 12 hours. Taking into consideration all of the blood glucose curves, the nadirs were most commonly observed after 6, 8, and 10 hours.

By week 24, polyuria/polydipsia had improved in 91% of the dogs. No clinical signs that could have been caused by hypoglycaemia were observed. Based on serial blood glucose curves and remission of the clinical signs for judging the success of the treatment, 58%, 33%, and 8% of the dogs attained good, moderate and poor glycemic control by week 24 of the study, respectively.

Conclusions
Insulin glargine administered subcutaneously twice daily is a possible and safe method of treatment for dogs with naturally occurring diabetes mellitus. Although only a few studies are available on the use of other types of insulin in dogs, their success rate is somewhat greater than that with insulin glargine.

My Bottom Line:

These results of this study suggest that insulin glargine administered subcutaneously twice daily is a valid method of treatment for naturally occurring diabetes in dogs, and that it is an alternative to other insulin preparations that have been shown to be effective in the treatment of canine diabetes (4,5,7-10).

In human patients, glargine is generally considered to be a peakless insulin (1). However, in the dogs of this study, a clear glucose nadir was identified in almost all of the blood glucose curves, indicating that the pharmacokinetics and pharmacodynamics of insulin glargine are not the same in dogs as they are in human beings.

In terms of the resolution of clinical signs achieved with insulin glargine, the results of this study were similar to those of other investigators using NPH insulin (7) or a lente insulin (8). The median insulin glargine dose at the end of the study (0.60 U/kg every 12 hours) was comparable with doses in other studies of NPH and lente insulins where insulin was administered every 12 hours (7,8).

It should be noted, however, that the median dose of glargine (0.6 U/kg) was much less than the median dose of PZI insulin (0.9 U/KG, BID) required for glycemic control in these diabetic dogs in a recent study (9).

Unfortunately, insulin glargine was not compared directly with other insulin preparations in this study. However, based on mean blood glucose concentration during 12-hour blood glucose curves, 58% of dogs in the present study obtained good control of hyperglycemia, which is less than the reported 75% of dogs with good control in a similar study where a porcine insulin zinc suspension (lente insulin) was used (8).

Therefore, although insulin glargine may be an acceptable insulin choice for some dogs with diabetes mellitus, the disease control success rate appears to be lower with glargine than with NPH or lente insulins (7,8). Certainly, if a more potent insulin preparation is needed (i.e., in a dog with insulin resistance), detemir insulin would be the insulin of choice, since determir appears to be at least  4-times more potent than the other insulin preparations which have been evaluated in the dog (10).

References:
  1. Owens DR, Bolli GB. Beyond the era of NPH insulin--long-acting insulin analogs: chemistry, comparative pharmacology, and clinical application. Diabetes Technology and Therapuetics 2008;10:333-349.
  2. Weaver KE, Rozanski EA, Mahony OM, et al. Use of glargine and lente insulins in cats with diabetes mellitus. Journal of Veterinary Internal Medicine 2006; 20:234-238.
  3. 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. Journal of Feline Medicine and Surgery 2009; 11: 683-391.
  4. 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.
  5. Mori A, Sako T, Lee P, et al.  Comparison of time-action profiles of insulin glargine and NPH insulin in normal and diabetic dogs. Veterinary Research Communications 2008; 32:563-573.
  6. Fracassi F, Boretti FS, Sieber-Ruckstuhl NS, et al. Use of insulin glargine in dogs with diabetes mellitus.  Veterinary Record 2012;170(2):52. 
  7. 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. Journal of Veterinary Internal Medicine 2009;23:50–55.
  8. 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.
  9. Maggiore AD, Nelson RW, Dennis J, et al. Efficacy of protamine zinc recombinant human insulin for controlling hyperglycemia in dogs with diabetes mellitus. Journal of Veterinary Internal Medicine 2012;26: 109-115.
  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; 90:396-103.