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

Abstract: Background: Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) warrant investigation as a therapeutic for insulin dysregulation

Hypothesis/Objectives: Velagliflozin, a novel SGLT-2i, decreases insulin concentrations in horses with moderate to severe insulin dysregulation (ID)

Animals: Privately owned adult equids (n=37) with moderate to severe ID (oral sugar test insulin concentration > 75 µIU/mL); 89% with a history of laminitis

Methods: A double-blinded placebo-controlled trial was performed with horses randomly assigned to receive placebo (n=19) or velagliflozin 0.3 mg/kg PO q24h (n=18) for 20 weeks. During a second 20-week period all horses received velagliflozin. Physical examinations and blood collections were performed at 0, 2, 4, 8, 12, 20, 22, 24, 28, 32, and 40 weeks. Placebo and velagliflozin groups were compared (Wk0-20). A mixed model for repeated measures ANOVA was used to assess effects of treatment, time, and treatment x time. Significance was set at P = 0.05.

Results – Day 0 insulin concentrations did not differ significantly between placebo and velagliflozin groups (P = 0.43). Treatment (P = 0.01), time (P < 0.01), and treatment x time (P < 0.01) effects were significant for plasma insulin concentrations when groups were compared Wk 0-20. Plasma insulin concentrations were significantly lower in the velagliflozin group, compared to the placebo group within 2 weeks (P=0.03). All horses exhibited an increase in serum triglyceride concentrations during velagliflozin treatment, but development of hypertriglyceridemia was not accompanied by clinical abnormalities (lethargy, anorexia).

Conclusions: Velagliflozin significantly decreased basal plasma insulin concentrations in horses with moderate to severe ID in this trial.