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

Overview

• This study tested the effects of bexagliflozin, a medication, on controlling high insulin levels in Arabian horses with naturally occurring insulin dysregulation.
• The researchers compared bexagliflozin treatment to a placebo to evaluate its safety and effectiveness in reducing insulin levels in these horses.

Study Design and Methods

• Type of study: Randomized, placebo-controlled crossover trial involving client-owned Arabian horses.
• Subjects: 10 Arabian horses with hyperinsulinemia (insulin > 30 μIU/mL).
• Interventions:
  • BEXA03: Bexagliflozin given at 0.03 mg/kg orally every 24 hours for 10 days.
  • Placebo control administered in crossover with a 4-day washout period between treatments.
  • After a 12-day washout from the initial phases, 8 horses received a higher dose of bexagliflozin (BEXA06: 0.06 mg/kg orally every 24 hours) for 7 days.
• Testing: Oral sugar tests were performed at baseline and after each treatment period to assess insulin and glucose responses.
• Measured parameters:
  • Insulin levels: resting, maximum concentration (Cmax), and area under the curve (AUC).
  • Glucose, triglycerides (fat in blood), and adipokines (hormones secreted by fat tissue).
• Data analysis used mixed-effects linear regression to compare treatment effects.

Key Findings

• High dose bexagliflozin (BEXA06) significantly reduced insulin measures compared to placebo:
  • Resting insulin decreased from ~54 μIU/mL with placebo to ~18 μIU/mL.
  • Maximum insulin concentration (Cmax) reduced from ~91 μIU/mL to ~48 μIU/mL.
  • Insulin AUC decreased substantially, indicating lower overall insulin exposure during the test.
• Low dose bexagliflozin (BEXA03) did not produce significant insulin reductions compared to placebo.
• Mild increases in triglyceride levels were observed in some horses after BEXA06 treatment, but average resting triglycerides were not significantly different from untreated controls.

Implications and Conclusions

• Bexagliflozin at 0.06 mg/kg given once daily is effective in controlling high insulin levels in Arabian horses with insulin dysregulation.
• The treatment had minimal effects on serum triglycerides, indicating it is relatively safe for short-term use regarding lipid metabolism.
• This study supports bexagliflozin as a potential therapeutic option for managing naturally occurring insulin dysregulation in horses, which is important because high insulin levels can lead to serious health problems in horses, such as laminitis.
• Further research would be needed to confirm long-term safety and clinical benefits.