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

Abstract

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&#x2009;=&#x2009;37) with laboratory-confirmed ID (low-dose oral sugar test insulin concentration&#x2009;>&#x2009;75 &#x3bc;IU/mL). METHODS: Double-blind randomized placebo-controlled trial. Horses received placebo (n&#x2009;=&#x2009;19) or velagliflozin 0.3&#x2009;mg/kg PO q24h (n&#x2009;=&#x2009;18) for 20&#x2009;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] &#x3bc;IU/mL in horses receiving velagliflozin and 157 [82-298] &#x3bc;IU/mL in horses receiving placebo; p&#x2009;<&#x2009;0.0001). The average (95% confidence interval [CI]) effect of velagliflozin treatment on insulin concentration was 155 (90-219) &#x3bc;IU/mL. Horses receiving placebo in SP1 had lower insulin (50 [26-99] &#x3bc;IU/mL) during SP2 (p&#x2009;<&#x2009;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&#x2009;=&#x2009;0.02) than those receiving placebo. CONCLUSIONS: Velagliflozin significantly decreased resting insulin concentrations in horses with ID.