The most common metabolic issue in horses is equine metabolic syndrome (EMS), noted Andrew van Eps, BVSc, PhD, MACVSc, DACVIM. (Learn about van Eps in the About section below.) Throughout this article, van Eps discusses treatments for equine metabolic syndrome, insulin dysregulation (ID), and pituitary pars intermedia dysfunction (PPID, or Cushing’s disease).

New medications—often borrowed from human medicine—have undergone research and show promise in treating some of these conditions in horses.

How Equine Metabolic Syndrome Affects Insulin Concentrations

Equine metabolic syndroms is the most common metabolic problem in horses, said van Eps. “It is linked closely with being overweight and is associated with a loss of sensitivity to insulin,” he explained.

In humans, blood glucose starts to rise as resistance to insulin develps, and the person produces more insulin to move that glucose out of the blood. “Eventually you run out of insulin and become a type-2 diabetic, unable to effectively control your blood insulin,” he said.

In horses, however, the problem tends to be the overproduction of insulin itself. “Unlike people, horses tend to just make more and more insulin,” he explained. “They generally don’t ever run out of insulin, and their blood glucose generally stays fairly well controlled. It’s that excess insulin that causes problems for horses, with the most important being laminitis.”

Treating Equine Metabolic Syndrome

Historically, equine metabolic syndrome has been managed with diet and exercise with very limited efficacy, said van Eps.

Researchers tried using the human diabetic drug metformin in horses. In humans, this drug lowers blood glucose and improves insulin sensitivity. “Unfortunately, metformin didn’t work well in horses,” he said.

Thyroxine, which is produced by the thyroid gland and helps control how the body turns food into energy, has been used extensively in horses to increase metabolic rate and consumption of energy and encourage weight loss. However, it tends to only be effective in the short term, said van Eps.

“What happens is there’s a sensitization that occurs to thyroxine, and it becomes not very useful after a certain amount of time,” he explained. “And that’s usually in weeks to months, not months to years.”

Newer Metabolic Medications

A major development in combatting metabolic issues and insulin dysregulation in horses is the availability of sodium glucose co-transporter 2 inhibitor (SGLT2i) drugs, noted van Eps. These are human diabetic drugs designed to promote the wasting of glucose in the urine, thus lowering blood glucose.

The first experiments with these drugs in horses took place about 15 years ago. Early research showed these drugs could lower insulin and even prevent secondary laminitis in carbohydrate challenge experiments in ponies.

“Now, these drugs are in fairly common use in horses and ponies and showing really good efficacy for encouraging weight loss and controlling and preventing laminitis that is due to high insulin,” said van Eps.

Ertugliflozin is the SGLT2i that equine researchers and clinicians have the most experience with. It has been used in many European countries and Australia, along with the U.S. in more recent years, with apparent clinical success. Other SGLT2i drugs (bexagliflozin, canagliflozin) are available and commonly used with good apparent effect in horses, but none are currently labelled for use in horses.

“Boehringer Ingelheim initiated the research work in horses, and they have gained approval in Europe and the U.K. for their drug velagliflozin (brand name Senvelgo),” said van Eps. “That’s probably coming to the U.S. at some point in the future (once it receives FDA approval).”

Why Is This Important?

Horses and ponies often live in environments where it is difficult to control food intake, explained van Eps. “This is something we’d suspected for a long time,” he added. “If you can lose weight, improve insulin sensitivity, and control carbohydrate intake, you can make a big difference even with horses that have established laminitis. You can improve them by controlling their insulin.”

He said in the last 100 years—and in the last 20 years in particular—horses have become much more like pets than working animals that do a lot of exercise. “So, what we are seeing is the consequences of that change,” said van Eps. “And those consequences are that insulin dysregulation and laminitis are more common than they used to be.”

Other Drugs on the Horizon

While SGLT2 inhibitors are very effective at lowering insulin, “as soon as you take them away, the effect is gone,” said van Eps. “So horses either need to stay on the drugs forever or something else has to change in the way that they’re managed. These drugs are more of a band-aid for insulin problems. You really need to change the husbandry, the feeding, and the exercise.”

Pioglitazone is another human anti-diabetic drug that has interested equine researchers.

“It works in a very different way,” said van Eps. “It has milder effects on insulin, but it encourages a change in the way the fat is distributed.”

Typically, visceral fat in your abdomen around your organs is “bad” fat that produces detrimental hormones and inflammatory mediators.

“Subcutaneous fat tends to be a healthier fat that actually has benefits,” he continued. “One of those is it secretes an adipokine called adiponectin. It tends to suppress inflammation, improve insulin action, and be protective against cardiovascular disease in people.

“In ponies, low adiponectin is a risk factor for laminitis independent of insulin.”

Adiponectin in Horses

Low adiponectin has previously been shown to have associations with both insulin dysregulation and laminitis in ponies. Van Eps’ research on adiponectin in light breed horses has shown that it seems to have similar associations. “If you have low adiponectin, that makes a horse more likely to have insulin dysregulation and also to have pre-existing laminitis based on X-ray,” van Eps said.

Pioglitazone is a drug that encourages redistribution of fat from the abdominal visceral into the subcutaneous compartment, he explained.

“Over time, that boosts adiponectin pretty significantly,” he said. “Our feeling is that boosting adiponectin in that way is likely to be protective against laminitis and also help with the underlying metabolic health of the animal.”

This means it is possible that drugs like pioglitazone might be helpful in the longer term, “more so than SGLT2 inhibitors, and we do use them in in conjunction.” said van Eps. “But, our understanding of this is still developing.”

He reminded owners that all of these drugs in the U.S. are still used off-label, meaning they’re not FDA-approved for horses.

A Different Adipokine

Leptin is another adipokine in horses. Veterinarians often test a horse’s leptin levels when evaluating their metabolic status. “Leptin is a bad guy. It’s produced by that visceral fat in the abdomen,” said van Eps. “So, high leptin tends to be associated with insulin dysregulation.

“But interestingly, the leptin’s never been really closely associated with laminitis, just insulin dysregulation in horses and ponies,” he added.

His research group will soon publish work about the ratio of leptin to adiponectin.

“In light breed horses, it’s more valuable than either of them alone as a marker of insulin dysregulation and as a marker of pre-existing laminitis as well,” van Eps said.

Sometimes, he said, the leptin-adiponectin ratio can give you an indication of what’s going on inside, and it isn’t always reflected by their outward appearance (i.e., the horse can be skinny or have a normal body condition despite having metabolic disease).

Relationship of PPID to Insulin Dysregulation

Horses can develop PPID once they reach their teenage years, with some horses getting the condition as young as 10. “That seems to tip their insulin regulation over the edge, and they’ll suffer laminitis sometimes,” van Eps said. “Perhaps they were on the edge of having laminitis for some time, but it seems to be a common theme that PPID can really tilt the balance. So, diagnosis and control of PPID is critical to preventing laminitis.”

Pergolide (brand name Prascend) is the only FDA-approved medication for treating PPID in horses. It is administered as a daily tablet. “It’s been available for a long time and seems to be fairly effective at reducing complications from the disease,” van Eps said.

Continued monitoring of blood ACTH levels is important so you can adjust the dose of pergolide when needed.

Some horses don’t respond well to pergolide. Van Eps mentioned the drug cabergoline, which works in the same way. However, this is an injectable drug that is used off-label in horses and ponies.

“It can be effective in animals that are refractory to high doses of oral pergolide,” he said.

What About Supplements?

Many supplements claim have an effect against PPID and insulin dysregulation. “The one that has had a little bit of research is resveratrol,” said van Eps. This is a compound from various plants that acts as an antioxidant.

“It does seemingly have some mild effects on improvement of insulin sensitivity,” he continued. “But there is not great science in horses behind that.

“If you have problems with laminitis, you’re always best off consulting your vet and making a plan that might involve some medication,” he added. “Use drugs when you have to, and use things we know work well rather than spending too much time and energy on supplements that may be expensive and unlikely to lead to meaningful improvement.”

Final Words

Veterinarians should monitor insulin in at-risk horses, but it can be difficult. “Insulin can fluctuate hour-by-hour,” stated van Eps. Today, there are easier ways to measure insulin than just a few years ago, including stall-side testing.

He reminded owners that stress and feed can affect insulin dramatically. “Insulin testing, particularly in response to the normal diet, can really be eye-opening,” said van Eps. “There can be specific components of the diet that trigger high insulin that sometimes are unexpected. It can be useful to test the insulin responses to specific feed components as part of a diagnostic workup in problem cases.”

Remember that grass stores starch (sugars) in response to sunlight. So, the highest risk of high sugar in pastures when horses are grazing tends to be late afternoon and early evening, after it has been light all day.

“The safest time for turnout is after a long period of darkness, so early morning up until about 10 or 11 a.m.,” said van Eps. “But even in the safest times, there could be too much starch in the pasture depending on the animal.”

About Dr. Andrew van Eps

Dr. Andrew van Eps is a professor, Section of Large Animal Internal Medicine, and the Dean W. Richardson Endowed Chair of Equine Disease Research at the University of Pennsylvania School of Veterinary Medicine’s New Bolton Center. He is an internal medicine expert whose research goal is to identify the key mechanisms that lead to different forms of laminitis in order to develop effective strategies for prevention and treatment. To learn more about van Eps’ research and how to support it, visit this website.

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    Kimberly S. Brown is an award-winning writer and publisher. She founded My Senior Horse for Equine Network and Linda Mars in her retirement, and now she is an editor of the brand. Brown previously had spent 10 years at Equine Network. Prior to that she worked for three years in equine nutrition after she retired from nearly 30 years working at The Blood-Horse. Brown spent the last 15 years of her time at that organization creating and developing the award-winning The Horse and TheHorse.com.

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