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 = 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.