To prevent diet-induced laminitis, sodium-glucose cotransporter 2 inhibitors (SGLT2i) have shown some success in limiting insulin response after eating. A 2022 Australian study — summarized by EquiManagement and originally published in Equine Veterinary Education — examined the use of ertugliflozin, a SGLT2i, to manage horses with laminitis and hyperinsulinemia. How hyperinsulinemia induces laminitis is unclear, though other studies have suggested that insulin may stimulate insulin-like growth factor-1 receptors within the lamellae, which promotes growth that leads to weakening and ultimately lamellar failure.
The study included 51 horses, the majority being pony breeds, including Welsh, Shetland and miniature ponies. All horses were unshod and regularly seen by a farrier.
“Other breeds included Quarter horses, Arabian/Arabian crosses and Warmbloods. Of the 51 horses, 23 were mares and 28 were geldings. The median age was 17 years. All horses had lameness as a result of laminitis, which had been present for a median of 41 weeks,” the study says.
Prior to administration of ertugliflozin, lameness and insulin concentrations were treated with at least 6 weeks of low-sugar hay feed at 1-1.5% body weight. When this method failed to reduce insulin concentration, each horse received 0.05 mg/kg ertugliflozin orally once daily for at least 30 days so long as they had not received supplemental medications such as metformin or levothyroxine. The study did not include a control group.
“A dozen horses were also diagnosed with PPID and treated with pergolide. Of the 51 horses in the study, 33 also received phenylbutazone at the time ertugliflozin treatment began,” EquiManagement says.
SGLT2is have recently been developed for the treatment of diabetes in humans but may also reduce insulin in horses through urinary glucose excretion, according to the study. In a 2018 and 2019 study where ponies were fed diets high in nonstructural carbohydrates, a different SGLT2i reduced hyperinsulinemia and prevented the development of laminitis. Another study in 2018 showed that a SGLT2i decreased the insulin response to an oral sugar test in horses when used with octreotide.
Study Results
Prior to treatment, median insulin concentrations in the participating horses exceeded 300 mlU/l. After 30 days of ertugliflozin, median insulin concentrations were reduced to 43 mlU/l.
“For the subset of horses with follow-up data beyond 30 days, insulin concentrations remained below baseline values, with a median concentration of 32 mlU/l for the samples taken between Days 60-240,” the study says.
Thirty-three of the 51 horses remained on treatment after 30 days because their insulin concentrations remained increased, and all 33 were sound and returned to previous activity levels. Ten of the remaining 18 discontinued treatment because laminitis and insulin had improved and were being managed through diet. The final eight no longer on treatment are unaccounted for, according to the study.
Prior to treatment, laminitis scores averaged 10 out of 12, whereas the median score was below two after 30 days of treatment. Triglyceride levels increased in 88% of horses at Day 30, from an average of 0.62 mmol/L to 1.4 mmol/L.
The authors of the study state that the use of ertugliflozin was associated with a reduction in insulin concentrations and lameness associated with laminitis and warrants further investigation.
Learn more about this study through EquiManagement and Equine Veterinary Education.
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