The sodium-glucose co-transporter 2 inhibitor velagliflozin reduces hyperinsulinemia and prevents laminitis in insulin-dysregulated ponies

Abstract

There are no registered veterinary drugs for treating insulin dysregulation and preventing insulin-associated laminitis in horses. Velagliflozin is a sodium-glucose co-transport 2 inhibitor that reduces renal glucose reabsorption, promotes glucosuria, and consequently, decreases blood glucose and insulin concentrations. This study aimed to determine if velagliflozin reduced hyperinsulinemia and prevented laminitis in insulin-dysregulated ponies fed a challenge diet high in non-structural carbohydrates (NSC). An oral glucose test (1 g dextrose/kg BW) was used to screen 75 ponies for insulin dysregulation, of which 49 ponies with the highest insulin concentrations were selected. These animals were assigned randomly to either a treated group (n = 12) that received velagliflozin (0.3 mg/kg BW, p.o., s.i.d.) throughout the study, or a control group (n = 37). All ponies were fed a maintenance diet of alfalfa hay for 3 weeks, before transferring to a challenge diet (12 g NSC/kg BW/d) for up to 18 d. Blood glucose and serum insulin concentrations were measured over 4 h after feeding, on d 2 of the diet. The maximum glucose concentration was 22% lower (P = 0.014) in treated animals, with a geometric mean (95% CI) of 9.4 (8.0-11.0) mM, versus 12.1 (10.7-13.7) mM in the controls. This was reflected by lower (45%) maximum insulin concentrations in the treated group (P = 0.017), of 149 (97-228) μIU/mL, versus 272 (207-356) μIU/mL for controls. The diet induced Obel grade 1 or 2 laminitis in 14 of the 37 controls (38%), whereas no velagliflozin-treated pony developed laminitis (P = 0.011). Velagliflozin was well-tolerated, with no hypoglycemia or any clinical signs of adverse effects. The main limitation of this study was the sample size. Velagliflozin shows promise as a safe and effective compound for treating insulin dysregulation and preventing laminitis by reducing the hyperinsulinemic response to dietary NSC.

Fig 1. Average rotation of the distal phalanx (degrees) taken from both front feet in ponies before and after a diet challenge period (DCP).

*P = 0.01 for comparison between pre- and post-diet challenge values using a paired Student’s t-test.

Fig 2

Geometric mean (95% CI) concentrations of insulin (A) and glucose (B) measured at 0, 60, 90, 120 and 240 min post-feeding on the second day of a diet challenge period in control ponies that developed laminitis (n = 11), control ponies that did not develop laminitis (n = 18) and velagliflozin-treated ponies (n = 12).