Bexagliflozin controls hyperinsulinemia in horses with naturally occurring insulin dysregulation: a placebo-controlled crossover trial

Objective: To evaluate bexagliflozin for insulin control in horses with naturally occurring insulin dysregulation. Methods: In a randomized, placebo-controlled crossover study, 10 client-owned Arabian horses with hyperinsulinemia (> 30 μIU/mL) were treated with bexagliflozin (0.03 mg/kg, PO, q 24 h; BEXA03) or placebo control for a 10-day treatment period, crossing over after a 4-day washout. After a further 12-day washout, 8 of the horses were treated with bexagliflozin (0.06 mg/kg, PO, q 24 h; BEXA06) for an additional 7-day treatment period. Oral sugar tests were performed at the beginning of each treatment period (untreated control) and on the final day of each treatment course. Insulin, glucose, triglycerides, and adipokines were compared with mixed-effects linear regression. Results: Mean resting, maximal (Cmax), and area under the curve (AUC) insulin were lower after BEXA06 (resting, 17.6 μIU/mL [95% CI, 5.3 to 29.9 μIU/mL]; Cmax, 48.4 μIU/mL [95% CI, 24.0 to 72.8 μIU/mL]; AUC, 4,084.0 μIU/mL*min [95% CI, 1,944.4 to 6,223.5 μIU/mL*min]) compared to placebo control (resting, 53.9 μIU/mL [95% CI, 35.0 to 72.7 μIU/mL]; Cmax, 90.9 μIU/mL [95% CI, 65.0 to 116.9 μIU/mL]; AUC, 9,146.3 μIU/mL*min [95% CI, 6,428.9 to 11,863.7 μIU/mL*min]), but not after BEXA03. Mild hypertriglyceridemia was observed in some horses following treatment with BEXA06 (n = 5), but mean resting triglyceride concentrations were not significantly higher for BEXA06 (49 mg/dL; 95% CI, 30 to 67 mg/dL) compared to the untreated control (32 mg/dL; 95% CI, 26 to 38 mg/dL). Conclusions: Bexagliflozin (0.06 mg/kg, PO, q 24 h) controlled insulin with minimal impact on serum triglycerides in Arabian horses with naturally occurring insulin dysregulation. Clinical Relevance: Treatment with bexagliflozin was effective for the short-term management of naturally occurring insulin dysregulation in horses.