The Modern Equine Vet
May 2024
Vol 14 Issue 5 2024
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Cover Story | Endocrinology

What Are the Options for Managing Insulin Dysregulation?

By Marie Rosenthal MS

A primary goal of controlling insulin dysregulation is to reduce the risk for laminitis, and there are several management options available, according to Emily Berryhill, DVM, who ran through a couple during a Burst Session held during the 69th Annual AAEP Convention.

The most effective method for managing insulin dysregulation is by diet and exercise. Veterinarians should recommend a diet that has fewer than 10% nonstructural carbohydrates (NSCs).

“However, some of these horses still need further reduction in NSCs,” she said, and a recent paper “proposed a threshold as low as 0.1 gram per kilo of NSC per meal.

“You can think about this as being really small, frequent meals throughout the course of the day for these horses that require low NSCs at each meal,” Dr. Berryhill suggested.

Unless the horse is already laminitic, exercise is also going to be critical.

“Diet and exercise together are better for improving insulin sensitivity compared with just managing diet alone,” she said.

Sometimes, however, diet and exercise are not enough, she admitted, so medications will need to be prescribed.

“When we think about some of the drugs that are out there, sodium glucose co-transporter 2 [SGLT2] inhibitors are kind of the drug du jour these days,” she said.

SGLT2 inhibitors are prescribed for people with type 2 diabetes with diet and exercise to lower blood sugar. The medications approved by the FDA for human use are canagliflozin, dapagliflozin and empagliflozin. Use in horses, however, is off label, she reminded, and data are limited.

“We’re learning more about them and using them more every day. They work by decreasing the amount of glucose that’s reabsorbed in the kidneys, and therefore, increasing the glucose excreted in the urine and reducing that drive for insulin production or release from the pancreas.”

This can be useful in 2 ways, she explained.

The first is in an emergency. Say, the horse is acutely laminitic, has “sky-high” insulin levels, and the horse needs to be stablized until the diet and management strategies are in place. “You need to help that horse in that moment, then potentially we can use these drugs for a short period while we’re getting everything else on board,” Dr. Berryhill suggested.

“The other time where we might use them is where you’ve already done everything you can possibly do. Your diet is great. You’re exercising, you’re managing the best you can, but the insulin is still not responding.”

In those cases, it might be useful to try 1 of these products.

“But it is important to note that these drugs are relatively new to us still,” she said, so the long-term safety data in horses are not available, yet.
It is important to watch for hypertriglyceridemia, one possible adverse event, Dr. Berryhill said.

“These are not drugs that you can just set and forget. I always recommend having a baseline insulin, having baseline triglycerides and liver enzymes,” she said, and start with the lowest possible dose of one of these medications, then titrating up if needed.

In addition, recheck the insulin levels, and discontinue if the triglyceride concentrations rise.

Also discontinue medication if the animal goes off feed for whatever reason. “Stop these drugs, get their metabolic system regulated again, and then you can think about restarting them—a horse that’s on these drugs and off feed is not going to be a good combination,” Dr. Berryhill said.

The dopamine agonist, pergolide, “definitely has its place in managing these guys if we’ve got concurrent PPID [pituitary pars intermedia dysfunction],” she said.

However, horses with PPID and insulin dysregulation may not respond as well to treatment, so it’s a good idea to get the PPID under control first and then check the insulin levels and put other mitigation strategies into place, Dr. Berryhill suggested.

Another option is metformin, which can be helpful with insulin sensitivity. This mainstay of human diabetes management, however, is poorly bioavailable in horses. Some horses seem to respond; some do not, she said. So, once again, check their insulin levels to assure the medication is working as expected.

Levothyroxine sodium (Thyro-L, Lloyd), which increases the horse’s metabolic rate, is an option, particularly if the horse needs to lose weight. However, this is a short-term solution, not something the horse should be on long-term because it downregulates receptors. Horses should be weaned off the treatment gradually, and restrict calories.

“If you’re giving a horse Thyro-L and they’re free fed out on a round bale, you’re shooting yourself in the foot,” Dr. Berryhill warned. “You’ve got to employ calorie restriction if you’re going to use Thyro-L.”

Although weight loss is another option for controlling hyperinsulinemia, she advised. “It is important to remember that not all obese horses are insulin dysregulated, and not all insulin dysregulated horses have to be obese.” MeV

For more information:

The studies below provide information about using SGLT2 medications in horses:

Meier A, Reiche D, de Laat M, et al. The sodium-glucose co-transporter 2 inhibitor velagliflozin reduces hyperinsulinemia and prevents laminitis in insulin-dysregulated ponies. PLoS One. 2018;13(9):e0203655. doi: 10.1371/journal.pone.0203655. eCollection 2018.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203655

Sundra T, Kelty E, Rendle D. Preliminary observations on the use of ertugliflozin in the management of hyperinsulinaemia and laminitis in 51 horses: A case series. Equine Vet J. 2022 Nov. 7.
https://beva.onlinelibrary.wiley.com/doi/full/10.1111/eve.13738

Lindåse S, Nostell K, Forslund A, et al. Short-term effects of canagliflozin on glucose and insulin responses in insulin dysregulated horses: A randomized, placebo-controlled, double-blind study. J Vet Intern Med. 2023;37(6):2520-2528.
https://onlinelibrary.wiley.com/doi/10.1111/jvim.16906