The effect of ertugliflozin on serum insulin and glucose in healthy horses receiving dexamethasone.

Overview

• This study investigated whether ertugliflozin, a sodium-glucose cotransporter 2 inhibitor (SGLT-2i), can reduce insulin dysregulation caused by dexamethasone treatment in healthy horses.
• The research found that ertugliflozin lowered daily serum insulin and glucose levels during dexamethasone administration, but did not improve insulin regulation after the drugs were stopped.

Background and Rationale

• Insulin dysregulation (ID) is a metabolic condition that can be worsened by corticosteroids like dexamethasone (DEX).
• Sodium-glucose cotransporter 2 inhibitors (SGLT-2i), such as ertugliflozin, are drugs that lower blood glucose by increasing its excretion through urine.
• SGLT-2 inhibitors are considered for managing insulin dysregulation, but their effect specifically on corticosteroid-induced ID in horses was previously unknown.

Objective

• To evaluate the effect of ertugliflozin on serum insulin and glucose concentrations in healthy horses receiving dexamethasone.
• The authors hypothesized that dexamethasone would induce insulin dysregulation and that coadministration of ertugliflozin would mitigate this effect.

Study Design

• Seven healthy horses were enrolled in a randomized crossover design study.
• Two treatment protocols were used:
  • DEX group: dexamethasone 0.06 mg/kg IV every 48 hours for 7 days.
  • SGLT-2i group: ertugliflozin 0.05 mg/kg orally every 24 hours plus dexamethasone as above for 7 days.
• Oral sugar tests (OST) and insulin tolerance tests (ITT) were performed before and after treatment to assess insulin sensitivity and glucose metabolism.
• Serum insulin and glucose levels were monitored throughout the treatment period.
• Data were analyzed using mixed-effects linear models to account for repeated measures and crossover design.

Key Results

• Insulin concentrations:
  • Mean daily insulin levels were significantly lower in the group receiving ertugliflozin plus dexamethasone compared to dexamethasone alone (P < .001).
  • Insulin levels showed consistency across two experiment blocks:
    • Block 1: DEX 50.6 μIU/mL vs. SGLT-2i 35.9 μIU/mL
    • Block 2: DEX 34.5 μIU/mL vs. SGLT-2i 18.9 μIU/mL
• Glucose concentrations:
  • Glucose levels were significantly lower in the ertugliflozin group on days 3 and 5 of treatment (P < .001).
  • Mean glucose concentrations:
    • Day 3: DEX 117.3 mg/dL vs. SGLT-2i 101.0 mg/dL
    • Day 5: DEX 116.6 mg/dL vs. SGLT-2i 101.0 mg/dL
• Post-treatment tests (OST and ITT):
  • Post-treatment oral sugar test showed increased insulin at 60 minutes (insulinT60) in both treatment groups, indicating that insulin secretion remained high (P = .01).
  • Insulin tolerance test results indicated that glucose levels decreased less in the SGLT-2i group compared to DEX alone after treatment discontinuation (P < .001), suggesting no improvement in insulin sensitivity.

Conclusions and Implications

• Ertugliflozin reduced mean daily serum insulin and glucose concentrations during dexamethasone treatment in healthy horses, indicating a beneficial effect on corticosteroid-induced hyperinsulinemia and hyperglycemia while the drug was administered.
• However, after stopping treatment, dynamic tests did not show improved insulin regulation, meaning the underlying insulin dysregulation caused by dexamethasone was not reversed by ertugliflozin.
• This suggests ertugliflozin may have short-term benefits in controlling glucose and insulin levels during corticosteroid therapy but might not provide a lasting solution to corticosteroid-induced insulin dysregulation.
• Further research would be needed to evaluate long-term effects, possible impacts on horses with preexisting insulin dysregulation, and clinical outcomes such as laminitis risk.