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

This is the authors' abstract. We don't add key points for this paper.

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.