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27-12-2011 | Article

New insulin preparation shows efficacy in diabetic dogs


Free abstract

MedWire News: A new long-acting human insulin preparation has shown preliminary efficacy for the treatment of dogs with diabetes mellitus, say US veterinarians.

Their findings suggest that recombinant human protamine zinc insulin (rhPZI) may be a useful alternative therapy in dogs that are poorly controlled on standard insulin preparations.

Commonly used insulins in dogs include recombinant human neutralprotamine Hagedorn (NPH) insulin and purified pork source lente insulin. Another option, insulin determir, has shown efficacy but is limited by its propensity to induce hypoglycemia.

In this study, Richard Nelson (University of California, Davis) and team evaluated rhPZI, which was recently approved for managing diabetes in cats, and may therefore have promise in other small animals.

The team studied 6 dogs newly diagnosed with diabetes mellitus and 11 with known diabetes but poorly controlled on their current insulin. All dogs were started on rhPZI therapy at a dose of 0.25-0.5 U/kg every 12 hours.

The dogs were reviewed on days 1, 7, 14, 30 and 60, and the insulin dose was adjusted to target, where "good" control was defined as a 10-hour mean blood glucose concentration below 250 mg/dL and a lowest blood glucose concentration during the 10-hour evaluation in the range 80-150 mg/dL.

Seventeen dogs completed the study and were included in the analysis. Breeds included Labrador Retriever, West Highland White Terrier, Chow Chow, Corgi, Beagle, Bichon Frise, Shih Tzu, Miniature Poodle, Chihuahua, Yorkshire Terrier, Blue Heeler, Brittany, and Cairn Terrier.

Six dogs were castrated males and 11 were spayed females. The median age was 10 years (range 4-16) and the mean body weight was 17.5 kg (range 5.2-44.5 kg).

Writing in the Journal of Veterinary Internal Medicine, Nelson et al report that the median rhPZI dose rose significantly between day 1 and day 60 (from 0.6 to 1.0 U/kg/injection).

Over the same period, 10-hour mean blood glucose concentration fell significantly (from 457 to 299 mg/dL), as did median lowest blood glucose concentration (from 397 to 204 mg/dL) and mean serum fructosamine (from 557 to 478 µmol/L).

By the end of treatment, 82% of owners said they had observed improvement in the severity of their dog's polyuria, polydipsia, and polyphagia. No dog gained weight and all dogs were determined to be in good condition on day 60.

In terms of toxicity, the only adverse event was hypoglycemia, which was asymptomatic in two dogs and symptomatic in three. In each of the latter cases, clinical signs resolved with feeding and a reduction in the rhPZI dose. There were no injection-site reactions.

Taken together, these preliminary findings support the efficacy of rhPZI in improving or maintaining control of glycemia, say the researchers, who advocate a starting dose of 0.5 U/kg every 12 hours.

They remark: "Inconsistency in blood glucose results in individual diabetic dogs was common, may be a reflection of prolonged duration of rhPZI effect, day-to-day pharmacokinetic variability of rhPZI in individual dogs, or both, and supports reliance on other indicators such as history, physical examination, stability of body weight, and serum fructosamine concentrations when assessing control of glycemia."

By Joanna Lyford