Blood pressure, electrolyte and fluid balance in horses with insulin dysregulation after short-term treatment with canagliflozin.

Overview

• This study investigated whether short-term treatment with the drug canagliflozin affects blood pressure, fluid, and electrolyte balance in horses with insulin dysregulation.
• Unlike in humans with type 2 diabetes, canagliflozin did not significantly change blood pressure, packed cell volume, serum proteins, or electrolytes in horses after three weeks of treatment.

Study Background and Purpose

• Canagliflozin is a sodium-glucose cotransporter 2 (SGLT-2) inhibitor used to treat type 2 diabetes in humans by lowering blood glucose levels.
• In humans, short-term treatment with SGLT-2 inhibitors often reduces blood pressure and causes changes in fluid and electrolyte balance.
• The study aimed to explore whether similar effects on blood pressure and fluid/electrolyte balance occur in insulin dysregulated (ID) horses following short-term canagliflozin treatment.
• Insulin dysregulation in horses is a condition related to abnormal glucose metabolism and can contribute to equine metabolic syndrome.

Study Design and Methods

• Design: Randomised, double-blind, placebo-controlled, parallel study conducted at a single center.
• Subjects: 16 privately owned horses and ponies diagnosed with insulin dysregulation.
• Baseline measurements were collected over three days before treatment, including:
• Serum electrolytes (such as sodium, potassium, etc.)
• Serum proteins
• Packed Cell Volume (PCV, a measure of red blood cell concentration)
• Blood pressure (systolic, diastolic, and mean arterial pressure) measured via non-invasive high definition oscillometry
• Intervention: Horses were randomly assigned to receive either canagliflozin at 0.6 mg/kg once daily or a placebo for a 3-week period.
• Treatment continued during a 3-day follow-up period, where the same measurements were repeated for comparison.
• The primary outcome assessed previously was glucose and insulin response; this paper specifically analyzed cardiovascular and fluid balance data.

Results

• Blood Pressure:
  • No significant change was detected in systolic, diastolic, or mean arterial blood pressure in the canagliflozin-treated group compared to placebo.
  • This contrasts with findings in humans, where SGLT-2 inhibitors typically cause a reduction in blood pressure during short-term treatment.
• Fluid Balance Indicators:
  • PCV, which indicates blood concentration and indirectly hydration status, showed no significant difference between treatment and placebo groups.
  • Serum protein levels remained stable regardless of treatment, suggesting no acute changes in plasma volume.
  • Serum electrolytes did not significantly differ between groups, indicating no acute electrolyte imbalance or disturbances.

Interpretation and Implications

• The absence of blood pressure reduction in insulin dysregulated horses suggests species-specific differences in the cardiovascular response to SGLT-2 inhibition.
• Unlike humans, horses treated with canagliflozin did not experience significant fluid shifts or electrolyte changes during short-term therapy.
• These findings imply that canagliflozin’s effects on blood pressure and fluid balance seen in humans may not translate directly to horses with insulin dysregulation.
• Understanding these species differences is important for potential clinical uses of canagliflozin or similar drugs in equine medicine.
• Further studies may be needed to assess long-term cardiovascular and metabolic effects of SGLT-2 inhibitors in horses.

Study Strengths and Limitations

• Strengths:
  • Randomised, double-blind, placebo-controlled design reduces bias and strengthens validity.
  • Use of non-invasive blood pressure measurement technique suitable for horses.
  • Controlled, repeated measurements before and after treatment.
• Limitations:
  • Relatively small sample size (16 animals), which may limit the ability to detect subtle effects.
  • Short duration of treatment (3 weeks), limiting insights into longer-term effects.
  • Study focused only on insulin dysregulated horses; other populations or disease states may respond differently.