What are the risks of elevated triglycerides in horses taking ertugliflozin (SGLT2 inhibitor)?

Risks of Elevated Triglycerides in Horses Taking Ertugliflozin (SGLT2 Inhibitor)

Horses treated with SGLT2 inhibitors like ertugliflozin are at significant risk for developing hypertriglyceridemia, which can range from mild to severe, and requires monitoring and potential intervention.

Prevalence and Severity

• Recent evidence shows that horses treated with SGLT2 inhibitors for hyperinsulinemia commonly develop varying degrees of hypertriglyceridemia, with 21% of cases showing triglyceride levels >2.0 mmol/L after 30 days of treatment 1
• Triglyceride levels can increase significantly from baseline, with median values doubling from 0.5 mmol/L to 1.0 mmol/L after 30 days of SGLT2 inhibitor treatment 1
• In severe cases, triglyceride levels can reach as high as 10.8 mmol/L 1

Risk Factors and Mechanisms

• Horses with higher baseline insulin levels, higher baseline triglycerides, and higher baseline very-low-density lipoprotein (VLDL) percentages are at greater risk for developing more severe hypertriglyceridemia 1
• SGLT2 inhibitors alter lipid profiles in horses, causing:
  • Increased serum triglycerides
  • Increased β-hydroxybutyrate
  • Increased total cholesterol
  • Decreased high-density lipoprotein (HDL) percentage
  • Increased very-low-density lipoprotein (VLDL) percentage 1

Clinical Manifestations and Complications

• Most horses with SGLT2 inhibitor-induced hypertriglyceridemia remain asymptomatic and maintain normal appetite despite elevated triglyceride levels 2
• However, severe cases can present with:
  • Weight loss (typically 6-10 weeks after starting therapy)
  • Colic symptoms
  • Potential progression to hyperlipemia requiring hospitalization 2
• Hypertriglyceridemia in horses can potentially lead to:
  • Hepatic lipidosis (fatty liver)
  • Reduced insulin sensitivity
  • Systemic inflammation
  • Multi-organ dysfunction if left untreated 3, 4

Monitoring Recommendations

• Baseline triglyceride levels should be measured before initiating ertugliflozin therapy 1
• Regular monitoring of triglyceride levels is recommended at:
  • 7 days after starting treatment
  • 30 days after starting treatment
  • Periodically thereafter, especially in high-risk horses 1
• Monitor for clinical signs of weight loss, decreased appetite, or depression, which may indicate worsening hypertriglyceridemia 2

Management of SGLT2 Inhibitor-Induced Hypertriglyceridemia

• For mild to moderate asymptomatic hypertriglyceridemia:

  • Continue monitoring while maintaining therapy if the benefits for insulin control outweigh the risks 2
  • Consider dietary modifications to mitigate triglyceride elevation 2

• For severe hypertriglyceridemia or symptomatic cases:

  • Discontinue the SGLT2 inhibitor (triglycerides typically return to normal within 7-10 days after discontinuation) 2
  • Consider intravenous dextrose administration for rapid triglyceride reduction 3
  • Partial parenteral nutrition may be necessary in severe cases 3

Prevention Strategies

• Select appropriate candidates for SGLT2 inhibitor therapy by screening for pre-existing risk factors for hypertriglyceridemia 1
• Consider lower starting doses of ertugliflozin with gradual titration to minimize metabolic disturbances 1
• Ensure adequate nutrition and avoid negative energy balance, which can exacerbate lipid mobilization 4
• Consider alternative treatments for hyperinsulinemia in horses at high risk for hypertriglyceridemia 2

Comparative Considerations

• Both dapagliflozin and ertugliflozin appear to have similar effects on triglyceride levels in horses, suggesting this is a class effect of SGLT2 inhibitors rather than specific to ertugliflozin 1
• The hypertriglyceridemia seen with SGLT2 inhibitors in horses differs from the effects seen in humans, where these medications generally do not significantly increase triglyceride levels 1