Phenylbutazone May Improve Insulin Dysregulation in Horses

The nonsteroidal anti-inflammatory drug phenylbutazone, frequently called bute, plays an important role in managing the pain associated with laminitis in horses with equine metabolic syndrome (EMS) and insulin dysregulation. Surprisingly, veterinary researchers found that phenylbutazone decreases insulin and glucose responses, thereby improving insulin dysregulation.^*

“This means that phenylbutazone holds the potential to act as a therapeutic agent for EMS,” explained Catherine Whitehouse, M.S., a nutrition advisor for Kentucky Equine Research.

To review, horses with EMS usually have hyperinsulinemia, which is high circulating levels of insulin. Elevated insulin levels result from increased production of insulin by the pancreas, decreased clearance of insulin from the circulation, insulin resistance, or a combination of these. Regardless, excess insulin levels in the bloodstream support the development of laminitis, specifically hyperinsulinemia-associated laminitis, which is currently the leading cause of laminitis in horses. Laminitis is an extremely painful condition often requiring medications such as phenylbutazone to relieve discomfort.

“In humans with type-2 diabetes, nonsteroidal anti-inflammatory drugs increase insulin secretion from the pancreas and decrease clearance from the bloodstream. This is the opposite of what we want to achieve in horses with hyperinsulinemia,” emphasized Whitehouse.

To determine the effects of phenylbutazone on glucose and insulin levels in horses, 16 light-breed horses received either phenylbutazone (4.4 mg/kg intravenously) or a placebo (saline) once daily for nine days. Of those, seven horses were identified as having insulin dysregulation (insulin concentration was greater than 80 μIU/mL), while the remaining nine horses were not (insulin concentration was less than 80 μIU/mL).

On day 9 of the study, all horses underwent an oral glucose test. Briefly, dextrose dissolved in warm water was administered directly into the stomach via a nasogastric tube. Blood samples were then collected periodically for the next six hours to measure insulin and glucose levels.

“Horses with insulin dysregulation treated with phenylbutazone had decreases in glucose and insulin concentrations in response to the oral glucose test compared to the placebo; however, researchers observed a lot of individual variability in how each horse responded. No significant effect of phenylbutazone was noted in control horses without insulin dysregulation,” Whitehouse revealed.

The researchers suggested several possible mechanisms by which phenylbutazone improves insulin and glucose levels, including the role of specific hormones. More research is required to explain these mechanisms.

While that research is being conducted, horse owners are advised to rely on established methods of lowering glucose and insulin levels in horses with insulin dysregulation.

“Weight management is important in equine metabolic syndrome, as episodes of weight gain and obesity can exacerbate insulin dysregulation and increase the risk of laminitis. As the grass starts to grow in spring, we often see rapid, significant weight gain, so it is important to be proactive in pasture management and restricting grazing in at-risk horses,” says Whitehouse. “It is also important to understand how individual horses respond to the diet, as some horses may be more or less sensitive to the amount of starch and sugar they can consume per meal and as part of the total diet.”

Kentucky Equine Research offers several products suitable for horses with metabolic conditions to promote health and wellness.

When dietary management does not sufficiently decrease insulin and the horse is suffering from hyperinsulinemia-associated laminitis, veterinarians may recommend a sodium-glucose-1 co-transporter 2 (SGLT-2) such as canagliflozin or ertugliflozin.

^*Kemp, K.L., J.E. Skinner, and F.-R. Bertin. 2024. Effect of phenylbutazone on insulin secretion in horses with insulin dysregulation. Journal of Veterinary Internal Medicine:17013.