HESTEFORSK: A novel therapeutic option for treating horses with insulin dysregulation and preventing laminitis H-19-47-479

Insulin dysregulation with high levels of insulin after feeding is one of the most common causes of laminitis in horses. The problem is greatest among easy keepers and hardy breeds, such as pony breeds and cold-blooded horses. Feeding restrictions often have limited effect and therefore the need to find a suitable drug that can prevent laminitis is the purpose of this study. In this study we examine the effect of different dosages of a human anti-diabetic drug, canagliflozin, which causes glucose to be excreted directly in the urine. Since glucose trigger the insulin response, the aim is to keep the insulin below the risk level for developing laminitis. In addition, we want to evaluate possible side-effects and long-term effects of using this medication. Individuals admitted to the study have been diagnosed with severe insulin dysregulation, have no clinical signs of laminitis and are not on any medication. As the study includes 2 stays at the Equine Hospital, the horses must be stabled within a reasonable transport distance from NMBU. During each stay, 3 different procedures are carried out where, among other things, the insulin response to glucose is measured. Between the 2 visits at the Equine Hospital, the horses are allocated to medication or placebo groups, decided by lottery. The horses that receive placebo participate in the long-term study where they are medicated for 4 months before new evaluations are performed. We have actively informed horse owners and veterinarians to recruit suitable candidates. The interest has been good, but many horses were excluded for various reasons such as transport problems or that the horse is/became laminitic. During 2022, a total of 7 horses have completed all the evaluations. All 7 horses have been in the hospital for 2 sessions, but one horse was withdrawn from the study due to acute laminitis and transport problems. One horse is participating in the long-term study and will be examined for the third time in January. The horses/ponies represent 5 different breeds. Two of the horses have not previously been diagnosed with laminitis. One was found to be at high risk of developing laminitis due to very high insulin values on the initial examinations. The response to treatment was very good, and the horse is now on an adjusted dose medication which hopefully will prevent laminitis in the future. All horses have completed the trial periods without any problems. They have settled in well at the hospital and are allowed to go outside in paddocks during the periods when they are not tested. All owners reported clinical response weekly between examinations and medication has worked as planned. Results so far show a clear response in all the horses that have been treated. All analyzes are not completed, but all horses that received the actual therapeutic drug normalized their glucose and insulin levels during treatment. The medication affects the horse`s metabolism, and fatty acid mobilization was increased in some horses, but none of the horses showed clinical signs of side effects and abnormal blood tests stabilized after a while. We will continue to recruit horses for the study through the winter and spring of 2023 and will then analyze all data and samples collected. The study is a collaboration with the Swedish University of Agricultural Sciences where they have examined many more individuals. Their results coincide with ours and together this will provide very good documentation of effect, dosage recommendations and possible side effects. The findings will contribute to the prevention of potentially fatal cases of laminitis in many horses.

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Insulin dysregulation (ID), a condition with excessive hyperinsulinemia, is the most common cause of laminitis in the horse. Insulin dysregulation is a core component of equine metabolic syndrome. Management strategies for ID include feeding diets low in non-structural carbohydrates, but excessive hyperinsulinemia is difficult to manage. There is thus a need for pharmacological treatment of ID. Canagliflozin, a new drug available in humans for treatment of type 2 diabetes, offers a novel therapeutic option for treating excessive hyperinsulinemia in the horse by inhibiting renal glucose reabsorption leading to urinary excretion of glucose. The overall aim of the present study is to investigate if a 4-week period of daily treatment with different doses of canagliflozin attenuates the hyperinsulinemic response to oral carbohydrates in insulin dysregulated horses to a level that would prevent insulin induced laminitis. In addition, any side effects during treatment will be documented.