Canagliflozin treatment of a horse with hyperinsulinemia, including pharmacokinetic analysis of different dosing protocols: a case report.

Laminitis is a complex and painful disease of the equine foot. Insulin dysregulation (ID) resulting in hyperinsulinemia is responsible for more than 90% of cases in the general horse and pony population. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a relatively new class of drug that has gained considerable popularity as an off-label treatment of hyperinsulinemia-associated laminitis (HAL) in horses when traditional management changes and treatments are unsuccessful. In Canada, canagliflozin is the SGLT2i most available to equine veterinarians; although no dosing protocols have been well-validated in horses, it is commonly administered orally at 0.6 mg/kg once daily. However, due to its long half-life in the horse, we hypothesized that every other day (EOD) dosing might be efficacious. Here we report the clinical outcome and pharmacokinetics of once daily versus EOD canagliflozin in a teaching horse with hyperinsulinemia and a history of severe laminitis. We found that insulin levels in this patient could be maintained within normal limits using EOD oral treatment of canagliflozin at a dose of 0.6 mg/kg. Daily dosing of canagliflozin led to accumulation resulting in approximately three times the drug exposure achieved with EOD dosing, where no accumulation was observed. Maximum plasma concentrations were 934.2 ng/mL after 30 days of single daily dosing and 324.3 ng/mL after 30 days of EOD dosing. This may be a promising new dosing strategy, although prospective trials in risk-matched populations are needed to assess the incidence of medication-associated adverse events and laminitis to determine the safety profiles of canagliflozin dosing strategies.