What is ertugliflozine and is it an effective treatment option for my laminitic horse’s EMS?

·10 November 2024

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Ertugliflozine is a medicine used to lower blood sugar levels in people with type 2 diabetes. It works by preventing the kidneys from reabsorbing glucose back into the body. Instead, the glucose is removed from the body through urine.

Weight loss and fluid removal

By excreting glucose through urine, the drug creates a calorie loss, contributing to weight loss. Additionally, it has a mild blood pressure-lowering effect, possibly due to its diuretic properties, increasing urine output.

For the extremely inquisitive among us, ertugliflozine is a sodium glucose cotransporter-2 inhibitor, or SGLT2i. Other examples of this class of drugs, which have also been tested in equines, include canagliflozine [1] and dapagliflozin.

For what horses?

Ertugliflozine may be prescribed by a veterinarian if dietary and exercise modifications —after truly exhausting all possibilities— and the potential use of the antidiabetic drug metformin are insufficient to control blood glucose levels, insulin values, and body weight.

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A good example is a severely lame horse with EMS/ID and significant obesity, unable to exercise sufficiently due to pain, even with therapeutic shoes. In a 2022 study, some of these horses, severely lame for months and unresponsive to dietary and exercise modifications, demonstrated remarkable improvement. Some were even able to canter happily in the field. Insulin levels decreased by an average factor of seven, and lameness scores on the 12-point modified Obel scale improved from 9.7 to 1.3 [2]. The researchers have not yet found an explanation for the latter, although it is certainly positive news.

Disadvantages

In human medicine, it is known that the increased glucose content in urine due to this medication can promote bacterial growth, potentially increasing the risk of urinary tract infections. Additionally, the diuretic effect may lead to an increased risk of dehydration. Whether these same risks apply to equines has not yet been studied. However, it has been observed that some treated horses exhibit increased water consumption and urination (polydipsia and polyuria) [3].

Polyuria and polydipsia: does your horse drink and urinate more than usual?

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Hyperlipidemia

Furthermore, blood fat levels increase during the first month of treatment. This is undesirable for EMS horses with hypertriglyceridemia, a specific type of blood lipid abnormality. Fortunately, these levels decrease again after this period, and the horses in this study did not exhibit any clinical signs associated with this condition [2].

Serious adverse events associated with SGLT2i

However, some horses have experienced more severe side effects from SGLT2 inhibitors. Cases have been reported where triglyceride levels were significantly elevated (<40 mmol/L), liver enzymes were increased, as were bile acids. This combination of abnormal blood values may indicate liver dysfunction or damage. It is advisable to have these blood values tested regularly. Acute kidney failure is a possible side effect in people [3]

Aforementioned horses also experienced further complications such as apathy, loss of appetite, gastric congestion, laryngeal paralysis (‘cornage‘), and even death [4]. Therefore, the use of SGLT2 inhibitors is not recommended in horses with liver problems or hyperlipidemia.

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Off-label

Since it’s not an FDA-approved drug for horses yet, veterinarians may prescribe the human version. This is known as off-label use. However, few veterinarians are currently doing so. This is because there is a lack of scientific studies supporting the efficacy and safety of ertugliflozine in horses, making many veterinarians hesitant to prescribe it.

To be sure and to avoid misunderstanding, the researchers in all cited publications emphasise that SGLT2 inhibitors are not a replacement for dietary and exercise modifications. These should always be implemented with care and dedication.

Now you want to know more. Much more.

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