Targeting Insulin Dysregulation in Horses: New Medication Tested

Insulin dysregulation is a central feature of equine metabolic syndrome. While diet and exercise remain the only recognized management options for affected horses, veterinary researchers are investigating a medication called pioglitazone, which is used in human patients with insulin dysregulation.

In horses, insulin dysregulation develops when the body fails to respond to insulin, a hormone that helps cells take up glucose from the bloodstream. Affected horses have elevated blood glucose as well as elevated insulin because the body tries to produce enough insulin to control the glucose.

“When prolonged, increased glucose and insulin levels negatively affect multiple body systems and put the horse at risk for laminitis,” added Catherine Whitehouse, M.S., a nutrition advisor for Kentucky Equine Research.

Once the notion of borrowing pioglitazone from human medicine came about, pharmacokinetic studies were performed in horses. These studies showed the ways the drug is specifically absorbed, metabolized, and excreted in horses. Pioglitazone showed favorable results, prompting additional studies. One study examined the effect of pioglitazone in 15 horses and ponies at a dose of 2 mg/kg by mouth once daily for 28 days.^*

“Each horse underwent an oral sugar test on days 14 and 28 of the study,” relayed Whitehouse. “This test is similar to the intravenous glucose tolerance test in that both tests measure the insulin and glucose levels in response to administration of sugar, which mimics a high-sugar meal like sweet feed or lush pasture.”

Horses and ponies administered pioglitazone had decreased insulin responses, suggesting that less insulin was required in treated horses to control blood sugar levels.

Pioglitazone functions by blocking a specific cellular receptor that results in the growth of fat cells that are more sensitive to the effects of insulin. These fat cells also produce more adiponectin, a powerful hormone that improves insulin sensitivity.

“In addition to decreasing insulin levels, pioglitazone administration also resulted in a significant increase in adiponectin concentrations,” Whitehouse relayed.

These results are extremely promising, and further study may make this medication available for clinical use. Even once this medication is available, animals with insulin dysregulation and metabolic syndrome should follow the recommended diet and exercise strategies outlined in the most recent guidelines published by the European College of Equine Internal Medicine. These recommendations center on achieving an ideal weight by losing between 0.5 and 1.0% of body mass per week. This goal can be realized by:

• Offering a forage-based ration totaling 1.4-1.7% body weight daily;
• Using forage with <10% nonstructural carbohydrates to limit increases in insulin;
• Feeding as little as 1.15% body weight of forage in horses/ponies “resistant” to weight loss;
• Eliminating treats from the diet, including cereal-based complementary feeds, fruits, or vegetables, such as carrots, apples, and high-fat feeds; and
• Routinely exercising overweight but sound horses and ponies.

“Should your horse require a ration balancer, which may be needed for hay-based, weight-control diets, look to a low-calorie product formulated by a reputable company,” Whitehouse recommended.

*Legere, R.M., D.R. Taylor, J.L. Davis, K. Bello, C. Parker, R.L. Judd, and A.A. Wooldridge. 2019. Pharmacodynamic effects of pioglitazone on high molecular weight adiponectin concentrations and insulin response after oral sugar in equids. Journal of Equine Veterinary Science 82:102797.