Human Drug Exenatide Holds Promise for Horses with Insulin Dysregulation

Veterinarians and researchers remain on the lookout for effective medications for horses battling insulin dysfunction. A medication called exenatide shows promise, according to a recent study.^*

“Insulin dysfunction refers to a horse’s inability to regulate blood insulin levels and metabolize nonstructural carbohydrates (NSC),” explained Katie Young, Ph.D., a Kentucky Equine Research nutritionist.

With insulin dysfunction, the tissues of the horse’s body, including the liver and muscles, fail to absorb glucose, or sugar, from the bloodstream after a high-NSC meal. The prolonged high levels of blood sugar stimulate the pancreas to produce excessive amounts of the hormone insulin in an attempt to bring circulating glucose levels back to normal. Horses with insulin dysfunction therefore have elevated insulin (hyperinsulinemia) and glucose levels in their bloodstream and are said to be insulin resistant. Insulin dysregulation can be determined through various laboratory tests, including the oral sugar test.

One of the main concerns for horses with insulin dysfunction is laminitis—a life-threatening condition requiring immediate and aggressive therapy. Specifically, high insulin levels directly damage the sensitive tissues of the foot called the lamella, which could lead to laminitis.

“Currently, while several research studies are investigating potential drugs to help regulate insulin and glucose in horses suffering from insulin dysfunction, the primary means of addressing insulin dysfunction are diet and management strategies,” said Young.

Current Management Strategies for Insulin Dysregulation

According to Young, “the most common strategies are regulating NSC intake of affected horses. This includes offering  feeds and forages containing lower or controlled levels of NSC, soaking hay to reduce the NSC content, and minimizing grazing access or using grazing muzzles to reduce fresh grass intake. Regular exercise may increase insulin sensitivity, and weight management also helps horses with insulin dysregulation as obesity can contribute to insulin resistance in some horses.”

She added, “These sorts of diets can be time- and labor-intensive for horse owners, considering the hay soaking and routine forage testing required.”

“It is important to ensure that horses on restricted diets receive rations supporting all nutrient requirements, even when focusing on weight loss. These horses typically require a low-intake ration balancer, especially when hay is soaked, which removes additional nutrients along with NSC, such as soluble proteins, vitamins, and minerals,” Young explained.

Looking Beyond Insulin: GLP-1

When horses ingest carbohydrates such as grains or concentrates, other hormones (in addition to insulin) are stimulated, such as glucagon-like peptide-1 or GLP-1. In humans, this hormone, also referred to as an incretin, stimulates insulin production, resulting in hyperinsulinemia. Research also shows that dogs treated with a GLP-1 analog, a drug that mimics GLP-1, has insulin-independent effects. Such effects include delayed gastric emptying and a decreased rate of glucose absorption.

“These insulin-independent effects of GLY-1 analogs may blunt the insulin response after a high-NSC meal,” Young explained.

This finding in dogs appeared to translate to horses as a small study showed that the GLP-1 analog exenatide did not stimulate excess insulin secretion in horses.

New Data on the GLP-1 Analog Exenatide

In a follow-up study, horses were administered a single dose of exenatide subcutaneously. Thirty minutes later, an oral sugar test was performed to assess insulin dysfunction by measuring glucose and insulin levels.^*

“A significant reduction in circulating insulin was reported as was reduced peak blood glucose concentration, and therefore an increase in insulin sensitivity,” Young said. “The researchers explained the results by proposing that exenatide improved the uptake of insulin and glucose in peripheral tissues, such as muscle, and thus enhanced whole-body insulin sensitivity, which would reduce the stimulus on the pancreas to release excess insulin into the bloodstream.”

These results suggest that exenatide exerts insulin-independent effects that temper the release of insulin into circulation following high-sugar meals. The GLP-1 analog exenatide may therefore prove to be an effective therapeutic for insulin dysfunction, which in turn may decrease the risk of hyperinsulinemia-associated laminitis.

^*Stefanovski, D., M.A. Robinson, and A. Van Eps. 2022. Effect of a GLP-1 mimetic on the insulin response to oral sugar testing in horses. BMC Veterinary Research 18(1):294.