Ertugliflozin decreases the insulin spike in non-insulin dysregulated standardbred horses following intra-articular triamcinolone administration.

Overview

• This study investigated whether the drug ertugliflozin can reduce the increase in insulin levels seen after corticosteroid injection in healthy horses.
• The results show that ertugliflozin significantly lowers the insulin spike following intra-articular triamcinolone administration compared to placebo.

Background and Rationale

• Horses with equine metabolic syndrome (EMS) often have abnormal insulin regulation and are more prone to laminitis, a painful hoof condition, especially after receiving corticosteroids.
• Corticosteroids like triamcinolone acetonide (TA) are used clinically but can cause harmful spikes in insulin levels that contribute to complications.
• Ertugliflozin is a sodium-glucose co-transporter 2 (SGLT2) inhibitor that reduces blood sugar and insulin levels.
• The study aimed to test if ertugliflozin could reduce the insulin spike caused by corticosteroids, potentially improving safety in horses.

Study Design

• The trial was a randomized, blinded, placebo-controlled, crossover study with eight adult Standardbred geldings without previous laminitis.
• Each horse received both treatments (ertugliflozin and placebo) in different periods, with a two-week washout in between.
• Horses were given either ertugliflozin orally at 0.05 mg/kg or a placebo once daily for four days before and four days after receiving an 18 mg intra-articular injection of TA into a carpal joint.
• The carpal joint chosen for injection alternated between the two treatment periods to control for side effects.
• Blood samples were collected twice daily during treatment to measure insulin, glucose, and triglycerides.

Data Analysis

• Bayesian statistical modeling was used to estimate the maximum plasma insulin concentration (Cmax) following the corticosteroid injection.
• This method provides credible intervals (similar to confidence intervals) and the probability of one treatment being better than the other.

Results

• The maximum insulin concentration (Cmax) after TA injection was significantly lower with ertugliflozin treatment (16.7 μIU/mL) compared to placebo (40.2 μIU/mL).
• The 95% credible intervals showed some variability but did not overlap substantially, indicating a clear difference between treatments.
• The probability that ertugliflozin resulted in a lower insulin spike than placebo was 99.13%, showing strong evidence of efficacy.
• No adverse effects or laminitis were reported in these non-insulin-dysregulated horses during the study.

Conclusions and Implications

• Oral ertugliflozin administration before and after intra-articular triamcinolone effectively reduced the corticosteroid-induced rise in plasma insulin in healthy Standardbred horses.
• This finding suggests that ertugliflozin could be a useful adjunct therapy to reduce insulin-related risks when corticosteroids are administered to horses, especially those predisposed to metabolic issues.
• Further studies would be needed to confirm benefits in insulin-dysregulated horses and to assess long-term safety and efficacy.