Metformin for Insulin Dysregulation in Horses: Magical or Mythical?

Contrary to previous research findings, a recent study reported that metformin did not help decrease insulin levels in horses following an oral sugar test (OST). Horses with high insulin levels and insulin dysregulation are at risk of laminitis, a painful and potentially life-threatening condition.

Insulin dysregulation refers to a condition in which a horse’s body cannot regulate insulin levels.

“Abnormally large releases of insulin following a meal, high levels of fasting insulin, and tissue insulin resistance are collectively termed insulin dysregulation. In all three of these instances, insulin levels in the blood are higher than normal, which is referred to as hyperinsulinemia,” explained Ashley Fowler, Ph.D., a Kentucky Equine Research nutritionist.

High levels of insulin are thought to damage the lamellae in the horse’s feet, causing laminitis. This form of laminitis is referred to as hyperinsulinemia-associated laminitis (HAL).

“Current treatment recommendations for insulin dysregulation include dietary restriction of nonstructural carbohydrates. Diets fed to horses with insulin dysregulation should contain less than 10% nonstructural carbohydrates. Because forage is the main component of the diet, it is important to test it for starches and sugars as forages can vary widely in carbohydrate content,” said Fowler.

In some horses, control of insulinemia cannot be achieved through dietary strategies alone. Thus, veterinarians look for alternate treatment strategies, including metformin.

Metformin is a medication used in human medicine for controlling type 2 diabetes. In humans, metformin enhances insulin sensitivity by (1) increasing glucose uptake by tissues, (2) inhibiting glucose production by the liver, and (3) decreasing intestinal absorption of glucose.

Metformin is used clinically in many horses, but studies supporting the use of this medication are contradictory in terms of whether it improves hyperinsulinemia and hyperglycemia.

To evaluate the ability of metformin to control glucose and insulin levels in horses after a meal, eight horses diagnosed with insulin dysregulation were identified.^* The horses were then administered a single dose of metformin (30 mg/kg), and an oral sugar test (OST) was performed. This OST protocol involved administering 0.45 mL/kg Karo light corn syrup to each horse and collecting blood samples 60 and 90 minutes after to measure glucose and insulin levels.

“Administering metformin prior to the OST had no effect on either glucose or insulin levels compared to the control group that only received a dose of water,” said Fowler.

That said, many limitations were noted in this study that may have affected those results, such as allowing access to feed prior to the test. Metformin has poor bioavailability and feeding horses may lower bioavailability further.

In addition to metformin’s affordability and safety, other researchers have reported positive effects of metformin under different conditions. Thus, the authors of this study suggested that in the HAL setting metformin could still have the potential for beneficial effects outside of insulin control.

“Currently, lowering nonstructural carbohydrates remains the cornerstone of treatment for insulin dysregulation. If forage with low nonstructural carbohydrates cannot be sourced, soaking hay is an effective way to reduce the sugar content. Soaking hay also reduces the concentrations of some essential nutrients, so adding a ration balancer or a vitamin and mineral supplement to the diet is important,” Fowler advised.

^*Colmer, S.F., A.A. Adams, E. Adam, R. Miller, D. Stefanovski, J.C. Kulp, and A. van Eps. 2023. The effect of pre-dosing with metformin on the insulin response to oral sugar in insulin-dysregulated horses. Equine Veterinary Journal:13979.