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An ultra-long-acting recombinant insulin for the treatment of diabetes mellitus in cats

Gilor et al. (2021). An ultra-long-acting recombinant insulin for the treatment of diabetes mellitus in cats. Journal of Veterinary Internal Medicine, jvim.16150. https://doi.org/10.1111/JVIM.16150

Diabetes mellitus is among the most common and serious endocrine diseases of cats. Perhaps the largest limitation to the treatment of diabetic cats is the need for insulin injections twice daily lifelong for many animals. Missed doses, inconsistent administration, and difficulty giving medications to cats all contribute to treatment failure, decreased quality of life, and damage to the human-animal bond.

This paper presents a preliminary report on an experimental ultralong acting insulin (AKS-267c). This molecule is created as a fusion of insulin with the Fc fragment of immunoglobulin, which is taken up intracellularly and recycled for a one-week period. This gives a one-week duration of activity after a single dose. This was designed as a dose escalation pilot study.

Cats were recruited from the University of California Davis Veterinary Medical Teaching Hospital and local veterinary clinics who had previously been diagnosed with diabetes mellitus (DM) and treated for at least two months with good glycemic control. No specific diet was required. Cats were excluded due to acromegaly, hyperthyroidism, or an insulin requirement >4 IU per dose. Blood glucose was measured using a flash glucose monitoring system.

Eight cats were screened for enrollment, of which 3 were excluded and 5 enrolled. The starting AKS-267c dosage was 0.83 (0.72-1.53) nmol/kg. Insulin dose was increased in 4 cats on week 2, and 3 further cats on week 3. After this, the dose was either maintained or decreased. The median final dosage of AKS-267c in the 5 cats was 1.11 (0.46-2.92) nmol/kg.

No adverse effect, injection site reaction, or hypoglycemic event was noted over the course of the study. Owners reported good control of clinical signs over the course of the study. There was also no significant change to median interstitial glucose, fructosamine, or body weight, suggesting an equivalency to standard care.

One cat achieved remission over the course of the study. The remaining four remained diabetic, however, the owners were required to continue the medication after study termination. One cat died of lymphoma (this cat was FIV positive) however the other 3 were maintained for 5, 5, and 18 months without issue.

Several limitations to this study exist. Among them are the small sample size and lack of long-term follow-up (many cats in reality will be treated with insulin for years). The study was underpowered to detect rare or even uncommon adverse effects of the drug, and the drug was not compared in a blinded fashion to the standard of care. While it serves as an adequate proof of concept, this paper does not demonstrate a product ready for market, and further work is needed. All cats were previously treated, as such investigation for this treatment in new diabetics was not performed.
Aside from methodologic issues, there are some concerns regarding a product such as this. Foremost amount them is the case of insulin overdose, in which case prolonged antihypoglycemic therapy may be required with such a long-acting drug.
Ultimately, the authors of this study concluded that the ultralong acting insulin formulation was safe and effective in this group of cats. Further work is needed prior to the commercialization of such a product, which may be revolutionary in the treatment of feline diabetes.
See Also
Gostelow R, Forcada Y, Graves T, Church D, Niessen S. Systematic review of feline diabetic remission: separating fact from opinion. Vet J. 2014; 202: 208- 221.

Niessen SJM, Hazuchova K, Powney SL, et al. The big pet diabetes survey: perceived frequency and triggers for euthanasia. Vet Sci. 2017; 4(2): 27.

Behrend E, Holford A, Lathan P, Rucinsky R, Schulman R. 2018 AAHA diabetes management guidelines for dogs and cats. J Am Anim Hosp Assoc. 2018; 54: 1- 21

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