Canagliflozin: Pharmacokinetics, tolerability and glucose/insulin effects of supratherapeutic doses in healthy horses.
Authors: Michanek Peter, Bröjer Johan, Lilliehöök Inger, Fjordbakk Cathrine, Erkas Malin, Löwgren Minerva, Hedeland Mikael, Bergquist Jonas, Ekstrand Carl
Journal: Veterinary journal (London, England : 1997)
Summary
# Editorial Summary: Canagliflozin Pharmacokinetics and Glucose Control in Horses Sodium-glucose co-transporter 2 inhibitors represent a potentially valuable pharmacological approach to managing hyperinsulinaemia-related laminitis in horses, yet clinical application has been hampered by limited safety and efficacy data specific to equine medicine. Researchers administered single oral doses of canagliflozin at 1.8 and 3.6 mg/kg to eight healthy Standardbred mares in a randomised, placebo-controlled crossover design, measuring plasma drug concentrations, insulin and glucose responses to a graded glucose infusion, and relevant serum and urinary markers over 72 hours. Both canagliflozin doses produced dose-proportional pharmacokinetics with peak concentrations reached within 2–3 hours and a half-life of approximately 22–23 hours, whilst significantly suppressing insulin responses (22–29% reduction in area under the curve) and moderately reducing glucose responses (14–15% reduction) compared with placebo. Urinary glucose excretion at therapeutic concentrations ranged from 277–347 mmol/L across the treatment period, with no clinically observable adverse effects, though the higher dose did produce a statistically significant elevation in glutamate dehydrogenase (GLDH), warranting monitoring for potential hepatic effects during longer-term use. These findings support further investigation of canagliflozin as a preventative strategy in insulin-dysregulated horses, whilst emphasising the need for controlled efficacy trials and longer-term safety assessments before clinical recommendation.
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Practical Takeaways
- •Canagliflozin effectively reduces insulin response in healthy horses, supporting its potential use for laminitis prevention in insulin-dysregulated horses; however, long-term safety and efficacy data in at-risk populations are still needed
- •The observed increase in liver enzyme (GLDH) at higher doses warrants monitoring during clinical use and suggests caution with dose escalation
- •Effective insulin reduction occurs at both tested doses without obvious clinical signs, allowing flexibility in dosing strategy pending further clinical trials
Key Findings
- •Canagliflozin showed dose-proportional pharmacokinetics with Cmax of 2623 ng/mL at 1.8 mg/kg and 4975 ng/mL at 3.6 mg/kg, with half-lives of approximately 22-23 hours
- •Insulin AUC was reduced 22-29% with canagliflozin compared to placebo following glucose infusion (p < 0.001)
- •Glucose AUC was reduced 14-15% with canagliflozin compared to placebo following glucose infusion (p < 0.001)
- •No clinical adverse effects observed, though GLDH levels significantly increased with the 3.6 mg/kg dose (p < 0.05)