Side Effects of Common Drugs Used in Horses for Insulin Dysregulation

More and more horses are diagnosed with hyperinsulinemia (high insulin levels in the bloodstream) and subsequently prescribed one of the “flozin” drugs, such as ertugliflozin, canagliflozin, or dapagliflozin. While generally viewed as safe, some horses develop abnormal fat levels, triglycerides specifically, in their bloodstream during treatment. Using data from 58 horses, researchers found only minor changes in lipid (fat) profiles and only occasional marked increases in triglycerides.^* Close monitoring of horses on these medications is indicated.

The “flozins” fall into the class of drugs called sodium-glucose cotransporter-2 inhibitors (SGLT2is). These medications block the resorption of glucose (sugar) from the kidney, resulting in decreased circulating levels. This lowers the release of insulin from the pancreas, reducing circulating insulin levels.

“High insulin levels cause laminitis, a common clinical feature of horses and ponies with insulin dysregulation and equine metabolic syndrome,” explained Catherine Whitehouse, M.S., a Kentucky Equine Research nutrition advisor.

Abnormally high levels of triglycerides in the bloodstream is a known side effect of the flozins. However, few horses show any clinical signs related to the elevated triglyceride levels, making it unclear how important this finding is.

Hoping to shed some light on this issue, veterinary researchers collected blood samples from 58 horses treated with either dapagliflozin or ertugliflozin. Blood samples were collected immediately prior to starting treatment (day 0) and then again on days 7 and 30.

“Triglyceride concentrations significantly increased from day 0 to day 30, reaching levels indicative of clinical hyperlipemia and supporting previous study findings. Other changes in bloodwork included increases in cholesterol and very low-density lipoproteins and decreases in high-density lipoproteins concentrations,” Whitehouse said.

For reference, high-density lipoproteins are referred to as “good” cholesterol in human medicine.

Other side effects were also infrequently reported, including excessive drinking and urinating, lethargy, and mild, intermittent diarrhea.

“Of interest to the researchers, it is unclear why treated horses tended not to show adverse clinical signs associated with the abnormal triglyceride levels. Only one horse had signs of colic and inappetence on day 7 with a very elevated triglyceride level. Treatment was discontinued and the horse improved over 24 hours with nutritional support,” Whitehouse shared.

Short-term flozin treatment, however, resulted in significantly decreased insulin levels, recovery from laminitis, and weight loss. This consistent, rapid response to therapy is what makes these drugs so attractive.

In this study, all six cases with markedly elevated triglycerides were treated with dapagliflozin. Previous studies found horses had high triglyceride levels with canagliflozin but not velagliflozin, suggesting that not all SGLT2is have the same effect on lipid profiles. Further studies are warranted.

In addition to relying on SGLT2is, nutritional strategies must be used to manage horses with insulin dysregulation and hyperinsulinemia.

“I highly recommend owners facilitate a collaboration between a veterinarian and an equine nutritionist to develop suitable feed programs. Horses receiving SGLT2is reportedly lose muscle mass in addition to fat, so it is important to provide adequate amounts of high-quality protein,” recommended Whitehouse.

“A ration balancer, such as All-Phase, that provides protein, vitamins, and minerals is a suitable feed option for these horses, as it is a low intake feed that doesn’t add significant calories or soluble carbohydrates. It can be fed in multiple small meals throughout the day, which decreases nutrient intake per meal and postprandial responses,” Whitehouse commented.

 ^*Sundra, T., E. Knowles, D. Rendle, E. Kelty, G. Lester, and G. Rossi. 2025. Short-term clinical and biochemical responses following treatment with dapagliflozin or ertugliflozin in horses with hyperinsulinemia: A retrospective case series. Domestic Animal Endocrinology 90:106894.