Can ertugliflozin (SGLT2 inhibitor) be used to treat diabetes in horses?

Ertugliflozin Use in Horses with Diabetes

Ertugliflozin should not be used to treat diabetes in horses due to lack of safety data and potential serious adverse effects including hypertriglyceridemia, which can be life-threatening in equines.

Understanding SGLT2 Inhibitors in Horses

SGLT2 inhibitors like ertugliflozin work by blocking glucose reabsorption in the kidneys, leading to increased urinary glucose excretion. While these medications are FDA-approved for humans with type 2 diabetes, their use in horses presents several important considerations:

Current Evidence in Equine Medicine

• Limited studies have explored SGLT2 inhibitors in horses, primarily focusing on insulin dysregulation rather than diabetes 1
• Horses with insulin dysregulation typically remain normoglycemic despite hyperinsulinemia, which differs from the human diabetic condition 1
• A recent retrospective study examined ertugliflozin at 0.05 mg/kg once daily in horses with hyperinsulinemia 2

Efficacy in Horses

• SGLT2 inhibitors can reduce serum insulin concentrations in horses with insulin dysregulation 2, 3
• In one study, ertugliflozin reduced basal serum insulin from median 170 μU/mL to 28.7 μU/mL after 30 days of treatment 2
• These medications have shown promise in managing laminitis associated with insulin dysregulation 4

Significant Safety Concerns

• Hypertriglyceridemia: A major concern with SGLT2 inhibitors in horses

  • 21% of horses developed significant hypertriglyceridemia (>2.0 mmol/L) after 30 days of treatment 2
  • Some horses developed severe hypertriglyceridemia (up to 10.8 mmol/L) 2
  • Hyperlipemia can be life-threatening in horses 5

• Lipid Profile Changes:

  • Increased triglycerides (median increase from 0.5 to 1.0 mmol/L) 2
  • Increased total cholesterol 2
  • Decreased HDL percentage and increased VLDL percentage 2
  • Increased β-hydroxybutyrate levels 2

• Other Potential Concerns:

  • Increased GGT levels suggesting possible hepatic effects 2
  • Risk of urinary tract infections (seen in humans) 6
  • Potential for euglycemic diabetic ketoacidosis 6

Clinical Implications

Risk Factors for Adverse Effects

• Pre-existing hypertriglyceridemia appears to increase risk of severe elevations during treatment 2
• Higher baseline insulin levels correlate with greater triglyceride elevations during treatment 2

Monitoring Recommendations (If Used Despite Risks)

If a veterinarian decides to use ertugliflozin despite the risks:

• Regular monitoring of triglyceride levels is essential
• Baseline lipid profile should be obtained
• Monitor renal function and liver enzymes
• Regular urinalysis to check for glucosuria and signs of urinary tract infection

Conclusion

While SGLT2 inhibitors like ertugliflozin show promise for managing insulin dysregulation in horses, they are not recommended for treating diabetes in horses due to:

1. Lack of FDA approval for veterinary use
2. Significant risk of hypertriglyceridemia, which can be life-threatening in horses
3. Limited understanding of pharmacokinetics and pharmacodynamics in equines
4. Fundamental differences between equine insulin dysregulation and human diabetes

Veterinarians should consider established treatments for equine metabolic disorders and consult with specialists in equine endocrinology before considering off-label use of human medications like ertugliflozin.