The effect of ertugliflozin on serum insulin and glucose in healthy horses receiving dexamethasone
Florence Dupuis-Dowd, Philip H Kass, Emily H BerryhillAbstract
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.