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

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT-2i) can be used to manage insulin dysregulation (ID). Their effect on corticosteroid-induced ID is unknown. Hypothesis/Objectives: Evaluate effects of ertugliflozin on serum insulin and glucose concentrations in horses receiving dexamethasone (DEX). We hypothesized that DEX would induce ID and ertugliflozin coadministration would mitigate that effect. Animals: Seven healthy horses. Methods: Randomized crossover design; horses received DEX (0.06 mg/kg IV q48h; DEX)or ertugliflozin (0.05 mg/kg PO q24h) plus DEX (SGLT-2i group) for seven days. Oral sugar (OST) and insulin tolerance (ITT) tests were performed before and after treatment. Insulin and glucose concentrations were measured during treatment. Data were analyzed using mixed-effects linear models. Results: Mean daily insulin concentrations were lower in the SGLT-2i compared with the DEX group (P < .001), with a block effect—mean insulin (95% CI) μIU/mL: Block 1 DEX 50.6 (42.1-59.1) and SGLT-2i 35.9 (28.1-43.7); Block 2 DEX 34.5 (27.8-41.3) and SGLT-2i 18.9 (16.5-21.4). Glucose was lower in the SGLT-2i group on days 3 and 5 (P < .001)—mean glucose (95% CI) mg/dL: Day 3 DEX 117.3 (110.4-124.3) and SGLT-2i 101.0 (95.7-106.4); Day 5 DEX 116.6 (107.9-125.3) and SGLT-2i 101.0 (95.5-106.4). Post-treatment OST insulinT60 was higher in both groups (P = .01). Glucose concentrations decreased less during the ITT post-treatment in the SGLT-2i group compared with DEX (P < .001). Conclusions and clinical importance: Ertugliflozin lowered mean daily serum insulin concentrations in horses receiving DEX. Dynamic tests after drug discontinuation did not indicate ID improvement.