Effects of the Sodium-Glucose Cotransporter-2 Inhibitor Velagliflozin on Insulin Concentrations in Horses With Insulin Dysregulation.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are promising treatments to manage hyperinsulinemia in horses with insulin dysregulation (ID). HYPOTHESIS: The SGLT2i velagliflozin decreases insulin concentration in horses with ID. ANIMALS: Privately-owned adult horses (n = 37) with laboratory-confirmed ID (low-dose oral sugar test insulin concentration > 75 μIU/mL). METHODS: Double-blind randomized placebo-controlled trial. Horses received placebo (n = 19) or velagliflozin 0.3 mg/kg PO q24h (n = 18) for 20 weeks (Study Period 1, SP1) immediately followed by a 20-week open-label trial where all animals received velagliflozin (SP2). Analysis of resting insulin, glucose, and triglyceride concentrations and body condition score (BCS) was performed between treatment groups and study periods using a Mann-Whitney U test. For SP1, analysis of changes in biochemical analytes over time was performed using generalized linear mixed effects models (GLMM). Data are reported as median (interquartile range). RESULTS: In SP1, GLMM indicated a significant effect of treatment on insulin concentration (71 [33-131] μIU/mL in horses receiving velagliflozin and 157 [82-298] μIU/mL in horses receiving placebo; p < 0.0001). The average (95% confidence interval [CI]) effect of velagliflozin treatment on insulin concentration was 155 (90-219) μIU/mL. Horses receiving placebo in SP1 had lower insulin (50 [26-99] μIU/mL) during SP2 (p < 0.0001). All horses experienced a transient increase in serum triglyceride concentration during velagliflozin treatment with no clinical abnormalities reported. In SP1, larger decreases in BCS occurred in horses receiving velagliflozin (median BCS 1 point lower than baseline; p = 0.02) than those receiving placebo. CONCLUSIONS: Velagliflozin significantly decreased resting insulin concentrations in horses with ID.