Large Animal Internal Medicine Resident University of California, Davis Davis, California, United States
Abstract: Background – Sodium-glucose cotransporter 2 (SGLT-2) inhibitors have proven their efficacy in managing insulin dysregulation (IR) and limiting hyperinsulinemia-associated laminitis, but the effect of SGLT-2 inhibitors on corticosteroid induced IR is unknown. Hypothesis/Objectives – To evaluate the effect of ertugliflozin, a SGLT-2 inhibitor, on insulin and glucose dynamics in healthy horses with concurrent dexamethasone administration. We hypothesized that dexamethasone would cause IR and that coadministration of ertugliflozin would mitigate that effect. Animals – Seven healthy research horses (four geldings and three mares). Methods – Utilizing a randomized crossover design, horses received dexamethasone (0.06mg/kg IV q48h) (DEX group), or ertugliflozin (0.05mg/kg PO q24h) plus dexamethasone (SGLT-2 group) for 7 days. Oral sugar (OST) and insulin tolerance (ITT) tests were performed before and after treatment, and daily serum insulin and glucose were measured during each treatment block. Data were analyzed with mixed effect linear models; P-value< 0.05 was considered significant. Results – Daily insulin concentrations were lower in the SGLT-2 group compared to the DEX group (P< 0.001) throughout treatment. Glucose was lower in the SGLT-2 group on days 3 and 5 (P< 0.001). The glucoseAUC and ∆insulinT60-0 from the OST were higher in both groups after treatment (P≤0.01, P=0.014, respectively), without difference between groups. Glucose concentrations decreased less during the ITT post-treatment in the SGLT-2 group compared to DEX (P< 0.001). Conclusions and Clinical Importance – Co-administration of ertugliflozin lowered serum insulin in horses administered dexamethasone but did not reduce IR. Ertugliflozin may reduce the risk of hyperinsulinemia associated laminitis in equine patients receiving corticosteroids.
