(E56) A Randomized, Placebo-controlled Crossover Study of Bexagliflozin Treatment in Horses with Naturally-occurring Insulin Dysregulation

Abstract:

Background: A bexagliflozin formulation registered for cats could effectively treat insulin dysregulation (ID) in horses.
Hypothesis/

Objectives: We hypothesized that the sodium-glucose cotransporter 2 inhibitor bexagliflozin would reduce the insulin response to oral sugar tests (OST) in horses with ID.
Animals: Ten client-owned Arabian horses (5-18 years; 442-571 kg) with naturally-occurring ID (mean OST maximal insulin 88 [range 51-157] µIU/ml).

Methods: Randomized, blinded, placebo-controlled crossover: 5 horses received placebo and 5 received 15 mg bexagliflozin once daily (~0.03 mg/kg; BEXA3) for 10 days. After a 4 day washout, treatments (swapped) were continued for 10 days followed by a 12 day washout. Then, all horses were treated with 30 mg bexagliflozin (~0.06 mg/kg; BEXA6) daily for 7 days. An OST (0.15 ml/kg Karo syrup) was performed at the beginning and end of each treatment period. Insulin (resting and OST) and triglycerides were compared (pre- vs post-treatment) using a mixed-effects linear regression model.

Results: Bexagliflozin treatment was associated with a mean [95% confidence interval] reduction in resting insulin (BEXA3: -15[-29 to -1.4]µIU/ml; BEXA6: -21[-35 to -6.5]µIU/ml); OST maximal insulin (BEXA3: -30[-51 to -8.8]µIU/ml; BEXA6: -46[-68 to -24]µIU/ml) and OST insulin area-under-the-curve (BEXA3 -2562[-4493 to -631] ]µIU/ml*min; BEXA6 -4154[-6168 to -2139] ]µIU/ml*min); P< 0.001. Resting serum triglycerides slightly increased with BEXA3 (40[31-49]mg/dl) and BEXA6 (52[43-61)mg/dl) compared to no treatment (32 [25-38]mg/dl); P< 0.001. No significant changes were associated with placebo (P>0.05).
Conclusions and Clinical Importance: In this cohort, short-term oral bexagliflozin treatment was effective for insulin control with only minor increases in serum triglycerides.