Treatment with ertugliflozin mitigates the hyperinsulinemic response to intra-articular triamcinolone acetonide.

Abstract

BACKGROUND: Intra-articular (IA) corticosteroids can cause hyperinsulinemia, which can subsequently increase the risk of laminitis, particularly in horses with insulin dysregulation (ID). Sodium glucose cotransporter 2 inhibitors (SGLT2i), a drug class that is being utilised more commonly in horses with insulin dysregulation, could potentially be used to control post-IA corticosteroid hyperinsulinemia. OBJECTIVES: To determine whether treatment with the SGLT2i drug ertugliflozin decreases hyperinsulinemia following intra-articular corticosteroid administration in metabolically normal horses. METHODS: Prospective, controlled, cross-over study design. Eight mixed-breed, metabolically normal geldings either received no treatment (CTL) or were treated with ertugliflozin (ERT) for 7&#x2009;days before and 7&#x2009;days after a total dose of 18&#x2009;mg of IA triamcinolone acetonide (TA). Samples for resting glucose and insulin concentrations, as well as dynamic oral sugar testing (OST), were collected. Treatments were crossed over and the study repeated. Two-way, repeated measures analysis of variance was used to identify timepoint by treatment differences (p&#x2009;<&#x2009;0.05). RESULTS: Insulin was significantly lower 2&#x2009;days after IA TA with ERT treatment at 60&#x2009;min post-OST. Resting glucose concentrations were significantly lower with ERT treatment at 8&#x2009;h, 12&#x2009;h, 24&#x2009;h, and 48&#x2009;h while resting insulin concentrations were significantly lower with ERT treatment at 12&#x2009;h, 24&#x2009;h, 48&#x2009;h, and 72&#x2009;h post-IA injection. MAIN LIMITATIONS: Non-insulin dysregulated horses and compounded ertugliflozin were utilised. CONCLUSIONS: Treatment with ertugliflozin decreases glucose and insulin changes following IA corticosteroid administration in metabolically normal horses. Further investigation of this treatment strategy in insulin dysregulated horses is warranted as it may reduce hyperinsulinemia and, therefore, the risk of laminitis with IA corticosteroid administration.