Hypertriglyceridemia in equines with refractory hyperinsulinemia treated with SGLT2 inhibitors

Abstract

Background: Sodium-Glucose CoTransporter-2 (SGLT2) inhibitors, the -flozin group of drugs, which block glucose reuptake in the renal proximal tubule, are being increasingly used off-label to treat horses with refractory hyperinsulinemia. After 2 years of use by animals in our group, a horse on canagliflozin was incidentally noted to be hyperlipemic.

Case description: We have been following a cohort of equines (n = 20) treated with SGLT2 inhibitors due to refractory hyperinsulinemia. The animals are owned by members of the Equine Cushing's and Insulin Resistance Group and treated by their attending veterinarians. The index case was a 23 years old gelding with a 2 years history of recurring laminitis that began canagliflozin therapy to control hyperinsulinemia which was no longer responsive to metformin. Between 6 and 10 weeks post start of therapy, significant weight loss was noticed. Two days later he was hospitalized with colic symptoms and hyperlipemia but was bright, alert, and eating well throughout. Canagliflozin was discontinued and triglycerides returned to normal reference values within 10 days. A subsequent study of 19 other horses on SGLT2 inhibitors revealed varying degrees of hypertriglyceridemia, all asymptomatic.

Conclusion: While this class of drugs holds great promise for cases of refractory hyperinsulinemia and laminitis that do not respond to diet or metformin therapy, hypertriglyceridemia is a potential side effect. In our experience, animals remained asymptomatic and eating well. Further study of hypertriglyceridemia in horses on SGLT2 inhibitors and the possible mitigating effect of diet is indicated. To our knowledge, this is the first report of hypertriglyceridemia with canagliflozin treatment in equines.

Keywords: Canagliflozin; Equine; Ertugliflozin; Hyperinsulinemia; Hypertriglyceridemia.

Fig. 1.. Box and whisker plots. Raw data for pre-treatment baseline (PRE), the first (R1) and second (R2) retest following SGLT2 inhibitor intervention. (A): Glucose (mmol/l); PRE n = 17, R1 n = 17, R2 n = 15. (B): Insulin (pmol/l); PRE n = 20, R1 n = 19, R2 n = 18. (C): Triglycerides (TG; mmol/l); PRE n = 10, R1 n = 12, R2 n = 12. (D): Log transformed triglycerides at pre-treatment baseline (PRE) and the first retest (R1).