Word of Caution When Treating Insulin Dysregulation and Laminitis

A new class of drug called sodium-glucose cotransporter-1 inhibitors (SGLT2i) are becoming popular for use in obese horses and ponies with insulin dysregulation and severe laminitis. Delivery of these drugs is often critical for horses and ponies struggling with quality of life. Any halo can become crooked, however, and experts are warning that owners and veterinarians should use caution with these medications.

Insulin dysregulation can easily be diagnosed using an oral sugar test. Once diagnosed, dietary modifications need to be instituted, which primarily reduce the intake of nonstructural carbohydrates (NSC).

“Horses with insulin dysregulation should be fed low-NSC forage (≤ 10-12% NSC), and we recommend owners have their hay tested to confirm NSC content. Hay can be soaked to reduce NSC if low-NSC hay cannot be sourced. Pasture access should be restricted or removed, as fresh grass typically contains large concentrations of NSC,” said Ashley Fowler, Ph.D., a nutritionist for Kentucky Equine Research.

When dietary management alone does not sufficiently control insulin dysregulation or laminitis, some veterinarians reach for the SGLT2i. As explained by Menzies-Gow and colleagues, these medications are used to control “equine hyperinsulinemia with the goal of improving recovery from associated active laminitis or preventing future laminitis.”^*

SGLT2i are hypoglycemic agents that increase urinary glucose excretion by blocking glucose reuptake in the kidneys. In turn, this results in urinary calorie loss with consequent weight loss. Examples of these drugs include the “gliflozins” such as velagliflozin, canagliflozin, and ertugliflozin.

“At this time, only limited clinical data are available in horses, with the bulk of the published work being uncontrolled, unblinded case studies. Further, only limited pharmacokinetic and pharmacodynamic studies looking at absorption, distribution, metabolism, and elimination of the drugs exist, and appropriate dosing studies have not been performed,” reported Fowler.

Instead, dosing information is largely extrapolated from human studies, which does not take into consideration species-specific variations in pharmacokinetics, pharmacodynamics, or toxicity.

Despite this, the SGLT2i appear safe. One study offering six times the “standard” dose of canagliflozin and another study using 10 times the “standard” dose of velagliflozin were tolerated well by horses.

One of the major concerns associated with SGLT2i is elevated levels of triglycerides, a type of fat found in the bloodstream.

“The observed hypertriglyceridemia appears to be short-lived; however, further long-term studies are needed to evaluate this feature,” Fowler shared.

In sum, Menzies-Gow and coworkers stated that only a small amount of evidence exists for using SGLT2i in the management of insulin dysregulation, and there “is no consideration of the fundamental differences between insulin dysregulation in horses and humans.”

For example, most horses with insulin dysregulation have normal glucose levels, suggesting that urinary loss of glucose may not fully explain the beneficial effects of SGLT2i in horses.

These medications are not first-line therapy, according to Fowler. Instead, diet should be altered to reduce NSC and prevent further exacerbation of insulin dysregulation. Even though these horses often require lower-calorie diets, their mineral and vitamin requirements are not reduced. A ration balancer or concentrated vitamin-mineral supplement should be added to the diet to ensure adequate intake of these essential nutrients.

 ^*Menzies-Gow, N.J. and E.J. Knowles. 2024. Sodium-glucose transport protein 2 inhibitor use in the management of insulin dysregulation in ponies and horses. Journal of Veterinary Pharmacology and Therapeutics: doi: 10.1111/jvp.13470.