Preliminary observations on the use of ertugliflozin in the management of hyperinsulinaemia and laminitis in 51 horses: A case series

Abstract

Background: Hyperinsulinaemia-associated laminitis (HAL) is encountered commonly in equine practice. There are currently no registered medications which specifically target hyperinsulinaemia in horses and ponies. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been demonstrated to limit post-prandial insulin responses and prevent the development of diet-induced laminitis. Objectives:The objective of the study was to evaluate the efficacy of an SGLT2i, ertugliflozin, in the management of hyperinsulinaemia and laminitis. Study design: Retrospective case series.Methods: Medical records of 51 horses and ponies that had presented with laminitis and hyperinsulinaemia and had been treated with oral ertugliflozin at 0.05 mg/kg once daily for a minimum of 30 days were reviewed.Results: After 30 days of treatment with ertugliflozin, there was a reduction in insulin concentrations from a median of >300 μu/ml (IQR: 149, >300) to 43 μu/ml (IQR: 20, 66) (p < 0.001). Modified Obel laminitis scores improved, reducing from a median of 10/12 to 1/12 (p < 0.001). Median serum triglyceride concentrations increased from 0.6 (IQR: 0.4, 0.9) before treatment to 1.4 (IQR: 0.8, 3.7) mmol/L after 30 days of treatment (p < 0.001) before declining, however, none of the horses developed any clinical signs of hyperlipaemia. Ten horses (19%) were reported to have polyuria and polydipsia during treatment, otherwise no adverse clinical effects were identified. Main limitations:The study was limited by the absence of a control group, the retrospective data collection and the short period of follow-up.Conclusions: Ertugliflozin may be effective in reducing insulin concentrations in horses and ponies with equine metabolic syndrome and its use may hasten recovery from laminitis associated with hyperinsulinaemia.

Hypertriglyceridemia in equines with refractory hyperinsulinemia treated with SGLT2 inhibitors

“…However, expanded monitoring revealed there was a significant increase in triglycerides at the first retest. Only three of our animals were on ertugliflozin but a similar pattern of asymptomatic increased triglycerides has been observed elsewhere in horses on ertugliflozin ( Sundra et al , 2022 ).…”

Sodium–glucose cotransporter 2 inhibitors in horses—Magic bullet or latest fad?

“…There was also a profound, and somewhat surprising, improvement in laminitis-associated lameness and the administration of ertugliflozin allowed cessation of non-steroidal anti-inflammatory (NSAID) treatment in virtually all cases within 2 weeks. 14 In a smaller case series, canagliflozin administered at 0.3-0.6 mg/kg PO SID was also associated with reduced insulin concentrations and resolution of lameness in horses with refractory hyperinsulinaemia and laminitis. 15 This dramatic improvement in comfort has been a consistent finding in laminitis horses treated with SGLT2i and is a potentially exciting development, which could improve the welfare of countless horses that are afflicted by HAL as well as reducing the risks associated with the use of NSAIDs.…”

“…19 Horses treated with ertugliflozin demonstrated significant weight loss after 30 days of treatment with a median reduction of 6% bodyweight over 30 days (range: 0.6%-19%). 14 Reduction in fat deposits has also been observed in horses treated with canagliflozin. 15 Pharmaceuticals will never be a substitute for dietary management and horse owners should be counselled on the importance of maintaining dietary restriction when using SGLT2i.…”

“…34 In contrast, hypertriglyceridaemia has been documented in horses treated with canagliflozin, ertugliflozin and velagliflozin although no adverse clinical effects have been reported to date. [14][15][16] Hypertriglyceridaemia has also been noted in cats treated with bexagliflozin without any associated clinical abnormalities. 35 Hypertriglyceridaemia following treatment with SGLT2i likely results from increased pancreatic glucagon secretion in response to reduced blood glucose and insulin concentrations.…”

A one-health approach to identifying and mitigating the impact of endocrine disorders on human and equine athletes

“…These drugs have been shown to have efficacy in treating refractive cases of EMS/ID, ones where the typical diet, exercise, and supplementation with metformin or levothyroxine has failed; limit insulin peaks after eating; and improve Obel scores. 42,43 Further investigation is required to determine if these new potential therapeutics are successful in a larger number of clinical cases and compared to other treatments.…”