Hyperinsulinemia-Associated Laminitis and Domestic Horse Welfare
Since first recognizing laminitis in ancient Greece, horse owners have attempted a slew of remedies to treat this painful and potentially life-threatening condition. Sodium glucose co-transporter-2 (SGLT2) inhibitors hold great promise for managing hyperinsulinemia-associated laminitis (HAL), the prevailing form of laminitis.
In the early 2000s veterinary researchers first noticed the vast majority of horses with laminitis had an underlying endocrine disease, primarily equine metabolic syndrome but also pituitary pars intermedia dysfunction (PPID, formerly known as equine Cushing’s).
“Not only should we have caught onto this sooner, we should also appreciate that HAL is a preventable condition,” said David Rendle, BVSc, MVM, CertEM (IntMed), Dipl. ECEIM, FRCVS, during his presentation at the Saratoga Vet & Farrier Conference, held Sept. 27-30, in New York. “However, despite greater understanding, we’re seeing more and more cases of HAL. This is a direct result of our failure to reduce the prevalence of equine obesity.”
Owners should manage their horses’ pasture intake, encourage exercise, and utilize the horse’s metabolism to burn calories to reduce obesity and limit hyperinsulinemia, said Rendle. “Just measuring resting insulin levels and knowing how a horse’s insulin concentrations respond to its normal diet is really helpful.”
Measuring a horse’s insulin levels and identifying whether they are at risk can help motivate owners to make the necessary management changes to prevent HAL, he added.
“Looking at human medicine, lifestyle changes are more effective than just using pharmaceuticals, but getting implementation/compliance is hard,” said Rendle. “As a profession we are understandably reticent to use pharmaceutical agents for a management-induced condition; however, the science of human behavior tells us that compliance with management changes will always present a major barrier to success.”
SGLT2 inhibitor drugs such as velagliflozin, ertugliflozin, and canagliflozin promote the kidneys to excrete glucose and, according to some studies and many anecdotal reports, are effective means of managing HAL.
In a study of 51 horses treated with 0.05 mg/kg ertugliflozin by mouth once daily, median insulin concentrations plummeted rapidly from a mean of over 300 U/L to 43 U/L in 30 days
“This is still higher than ideal but is much better than 300 U/L and much better than you will achieve with management alone,” noted Rendle.
Ertugliflozin rapidly and profoundly improves laminitis scores and lowers insulin levels, with most horses achieving soundness and abrogating the need for phenylbutazone within two weeks of initiating treatment.
“We also noted a decreased body weight and morphometric measurements such as belly girth,” Rendle added.
Surveys of horse owners show they are eagerly embracing SGLT2 inhibitors because their horses’ pain levels improve profoundly with the use of these drugs. This improvement is so dramatic that of those owners considering euthanasia as a result of their animal’s suffering, 80% reported their horses had mild or absent pain after 30 days of treatment.
The researchers noted hyperlipidemia (high blood fat levels) in treated horses, but Rendle said this rarely translates from the laboratory into a clinical problem.
SGLT2 inhibitors are a promising group of drugs, but horse owners and veterinarians should appreciate that long-term follow-up data are lacking, the medication is expensive in the U.S. and not always widely available, and the full safety profile of these medications has not been explored.
“SLGT2is appear effective but it’s still early days. And owners need to appreciate that HAL is a disease of management,” said Rendle. “Diet and exercise are central to controlling weight and insulin levels. SGLT2is are not a get-out-of-jail card or a substitute for implementing appropriate management strategies for preventing and treating obesity.”
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