Canagliflozin effectively cuts hyperinsulinemia in insulin-dysregulated horses but increases triglycerides

Insulin dysregulation (ID) is a prevalent and debilitating condition in horses, leading to diminished welfare and increased risk of laminitis. Current management strategies primarily rely on dietary modifications and exercise, which often yield variable responses and offer limited medical options for effectively controlling hyperinsulinemia. Sodium-glucose cotransporter-2 (SGLT2) inhibitors represent a promising pharmacological approach by promoting renal glucose excretion, thereby potentially mitigating the elevated insulin levels characteristic of ID horses.

This multi-center, randomized, double-blind, placebo-controlled, parallel-group study enrolled 42 privately owned, severely ID horses. Animals were allocated (1:1:1) to receive either canagliflozin 0.6 mg/kg PO q24h, canagliflozin 1.2 mg/kg PO q24h, or placebo for a 4-week at-home treatment period. The study included a 5-day baseline and a 5-day follow-up evaluation. During each clinical visit, an Oral Sugar Test (OST) and a Forage-based Feed Challenge Test (FCT) were performed to assess glucose and insulin responses, with adverse effects meticulously recorded.

Canagliflozin treatment significantly lowered peak insulin concentrations during both the OST and FCT compared to placebo (P ≤ .01). For the OST, peak insulin was 122.0 μIU/mL (95% CI: 96.6-154.0) for the 0.6 mg/kg group and 108.6 μIU/mL (95% CI: 85.6-137.8) for the 1.2 mg/kg group, compared to 288.7 μIU/mL (95% CI: 227.1-366.9) for placebo. Similarly, during the FCT, peak insulin was 78.3 μIU/mL (95% CI: 37.6-162.9) and 54.2 μIU/mL (95% CI: 25.7-114.5) for the 0.6 mg/kg and 1.2 mg/kg groups, respectively, versus 140.3 μIU/mL (95% CI: 68.5-287.3) for placebo. This demonstrates a robust reduction in hyperinsulinemia. However, canagliflozin also induced a dose-dependent increase in triglyceride concentrations (P ≤ .01).