11/10/2023
The war against hyperinsulinemia to prevent laminitis rages on.
In 2022, we were delighted to announce preliminary findings of very favorable responses to canagliflozin (Invokana®) in severely laminitic horses with hyperinsulinemia unresponsive to the usual diet and drug therapy. Kellon and Gustafson (2022)
In the two years we monitored case reports, no adverse effects were reported until a horse was noted to be hyperlipidemic (high blood triglycerides). The horse was hospitalized as a suspected colic but continued to be bright and eating well with triglycerides coming down rapidly with therapy and off the drug.
We immediately informed owners and their treating veterinarians of the risk of hyperlipidemia/hypertriglyceridemia and advised screening both before therapy and serially after starting therapy. We have found that the vast majority of horses on canagliflozin or ertugliflozin develop high triglyceride levels. Detailed information on these cases has been recently published. Kellon and Gustafson (2023). https://pubmed.ncbi.nlm.nih.gov/37026076/
Except for mild to moderate weight loss, these horses showed no evidence of the life-threatening hyperlipemia syndrome reported in donkeys, ponies, and miniature horses. We also found that animals in those high-risk groups for hyperlipemia did not develop more severe hypertriglyceridemia with these drugs. We believe the hypertriglyceridemia is in response to an energy shortage caused by the loss of glucose in the urine, similar to what occurs with fasting/starvation and during endurance exercise.
While our 2023 paper was under review, Sundra, et al. (2022) reported on responses to ertugliflozin in horses in Australia. They found similar triglyceride elevations without symptoms. This is consistent with the report of Dunkel, et al. (2013) where it was noted horses with metabolic disorders may be hyperlipidemic for many years, including with liver enzyme elevations, yet show no obvious ill effects.
Nevertheless, because of the potential for development of fatty liver we recommend diets be liberalized to free-choice safe hay and 1 to 2 lbs of beet pulp daily for full-size horses. This allows for an increase in safe calories and the acetate from fermentation of beet pulp and hay can substitute directly for glucose. Other dietary measures are also being investigated.
We wish to especially recognize the members and volunteers of the ECIR Group Inc. for their contribution of time, resources, and data, without whom help for metabolic equines would not be possible.
REFERENCES
Kellon EM, Gustafson KM. (2022) Use of the SGLT1 inhibitor canagliflozin for control of refractory equine hyperinsulinemia and laminitis. Open Vet J. 12:511-518.
Kellon EM, Gustafson KM. (2023) Hypertriglyceridemia in equines with refractory hyperinsulinemia treated with SGLT2 inhibitors. Open Vet J. 13:365-375.
Sundra, T., Kelty, E. & Rendle, D. (2022) Preliminary observations on the use of ertugliflozin in the management of hyperinsulinaemia and laminitis in 51 horses: A case series. Equine Veterinary Education, 00:1– 10.
Dunkel B, Wilford SA, Parkinson NJ, Ward C, Smith P, Grahame L, Brazil T, Schott HC 2nd. (2014) Severe hypertriglyceridaemia in horses and ponies with endocrine disorders. Equine Vet J. 46:118-22.
