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SGLT2 inhibitors, also known as flozins, are emerging as a novel therapeutic option in equine medicine, particularly for horses and ponies affected by severe insulin resistance and endocrinopathic laminitis.
Interest in these medications has increased rapidly in recent years as veterinarians look for additional tools to manage difficult metabolic cases that do not respond adequately to traditional management and therapies.
Originally developed to manage diabetes mellitus in humans, these medications block specific transport protein activity in the kidneys, which leads to excretion of glucose (sugar) in the urine. In horses, this mechanism can help lower circulating insulin concentrations and support management of horses with equine metabolic syndrome.
As research into equine metabolic disease continues to evolve, SGLT2 inhibitors are becoming an increasingly important topic for horse owners, veterinarians, and trainers managing horses with recurrent laminitis and severe insulin dysregulation. Understanding how these drugs work, along with their benefits, limitations, and potential risks, is essential before considering their use in any horse.
SGLT2 Inhibitors for Horses
SGLT2 inhibitors are a group of medications used to manage diabetes in people. More recently, these drugs have been explored as a management strategy for equine metabolic syndrome and insulin resistance in horses. [1][2]
In equine practice, interest in SGLT2 inhibitors is focused mainly on horses and ponies with marked insulin dysregulation, especially those at risk of recurrent or ongoing laminitis.
These cases can be difficult to manage with diet, exercise and weight loss alone, making additional therapeutic options an important area of investigation.
Rather than directly increasing insulin sensitivity, SGLT2 inhibitors act through the kidneys to promote glucose loss in the urine. [2] This effect may help lower circulating insulin concentrations in some horses, which is the main reason these drugs are being studied for metabolic and laminitis-prone equine patients.
The SGLT2 inhibitors most commonly discussed in human and equine medicine are often called flozins because many drugs in this class share the “-flozin” suffix. Examples include: [1][2]
- Canagliflozin
- Ertugliflozin
- Dapagliflozin
- Velagliflozin
Of these, canagliflozin and ertugliflozin are the most studied in horses. Velagliflozin has also been reported in equine research, while other drugs in this class are better established in human medicine than in horses. [1]
Because SGLT2 inhibitors are not approved specifically for horses, their use is off-label, also referred to as extra-label. Off-label prescribing is permitted under veterinary regulations at the veterinarian’s professional discretion.
Available Forms
Canagliflozin is available under the brand name Invokana® in the United States and Canada. Generic formulations are also available in Canada.
Brand names of ertugliflozin include: [3]
- Segluromet®
- Steglatro®
- Steglujan®
Both drugs are available as oral tablets with a prescription from a veterinarian. In some areas, ertugliflozin is also available in capsules, oral liquids, or oral pastes to facilitate administration to horses.
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What's your top priority with your horse's health?
Drug Class: SGLT2 Inhibitors
SGLT2 inhibitors are a class of antidiabetic medications that help lower blood glucose by increasing glucose loss through urine. [2]
They are also referred to as:
- Sodium-glucose cotransporter 2 inhibitors
- Gliflozins
- Flozins
This class includes drugs such as canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin. In veterinary medicine, bexagliflozin and velagliflozin are approved in the United States for improving glycemic control in certain cats with diabetes mellitus. [3]
In horses, SGLT2 inhibitors are being investigated and used clinically for insulin dysregulation, but their use remains extra-label and must be obtained from a licensed veterinarian.
Mechanism of Action
SGLT2 inhibitors target sodium-glucose cotransporter 2 (SGLT2), a protein found in the kidneys. This protein’s main role is to reabsorb glucose that enters the urine. [2]
In conditions such as diabetes, excess sugar in the bloodstream is filtered into the urine by the kidneys. SGLT2 then transports some of that glucose back into the bloodstream, preventing it from being excreted. [4]
SGLT2 inhibitors block this transporter from reabsorbing glucose. [2] As a result, more glucose is excreted in the urine, which can help lower or stabilize blood sugar levels.
This is particularly important in diabetic patients, where persistent high blood sugar contributes to complications such as renal disease, blindness, vascular disease, and nerve disorders. [4]
Uses in Horses
SGLT2 inhibitors are used in horses to manage Equine Metabolic Syndrome (EMS), which shares key characteristics with diabetes mellitus but is not the same condition. Horses with EMS have insulin resistance, meaning their cells do not respond to insulin appropriately. [1]
Under normal circumstances, insulin is released from the pancreas in response to increased blood sugar, usually after eating a meal. As the meal is digested and sugar is absorbed, insulin signals the body’s cells to absorb glucose for energy. As blood sugar levels decline, insulin release also declines. [5]
In animals with insulin resistance, insulin is released normally, but the cells do not respond effectively. As a result, glucose remains in the bloodstream, which can trigger additional insulin release from the pancreas.
This leads to hyperinsulinemia (high blood insulin) and hyperglycemia (high blood sugar), with little glucose being taken up by the tissues. [1]
For horses with equine metabolic syndrome, one of the main consequences of hyperglycemia and hyperinsulinemia is laminitis. This is a severely painful and life-threatening condition affecting the laminae, the tissues that connect the coffin bone to the hoof wall.
Using SGLT2 inhibitors may help clear excess glucose from the bloodstream, which may reduce the risk of laminitis. [1]
SGLT2 inhibitors are used off-label in horses. This means there is no equine-specific formulation approved by the Food and Drug Administration or Health Canada. [1][3] In these cases, veterinarians may prescribe human formulations based on available research and clinical experience.
Administration Routes
SGLT2 inhibitors are oral medications that are typically given once daily. [3] Human formulations are usually sold as tablets, although compounding pharmacies may be able to prepare oral liquids or pastes to make administration easier for horses.
Because SGLT2 inhibitors are not approved for use in horses, there is no standardized equine dosage. Little is currently known about how these drugs are absorbed and processed in the equine body.
Veterinarians use available studies, previous experience, and bloodwork monitoring to determine an appropriate treatment plan for the individual horse. Dosage may also vary depending on the specific drug used and the formulation prescribed.
Storage
Tablets should be stored in a dry place and protected from moisture. Keep them at room temperature and avoid extreme temperatures. [3]
Keep out of reach of children and animals.
Safety Warnings & Precautions
SGLT2 inhibitors are generally considered safe drugs with few reported adverse reactions. Monitoring focuses on whether the medication is effectively lowering insulin and glucose levels and on ensuring the horse does not become dehydrated during treatment.
Monitoring
Horses receiving SGLT2 inhibitors should be monitored closely to assess how well the treatment plan is working.
Veterinarians typically recommend baseline bloodwork before starting medication, followed by repeat bloodwork 2 to 4 weeks later. Insulin and glucose levels are particularly important to monitor.
SGLT2 inhibitors can cause polyuria, or excessive urination. Monitor horses closely for signs of dehydration and ensure they have unlimited access to water during treatment. [1] It is also important to track appetite and body condition score for any changes during therapy.
Contraindications
Contraindications refer to circumstances where a drug should be avoided or used with caution.
SGLT2 inhibitors should not be used in horses that have had a previous hypersensitivity reaction to these drugs. They should also be used cautiously in horses predisposed to dehydration because of management factors, concurrent medications, or other medical concerns.
In humans, SGLT2 inhibitors are not recommended during lactation or during the second and third trimesters of pregnancy. [3]
Reproductive safety has not been established in horses. In general, veterinarians use these drugs in pregnant or lactating mares only when the maternal benefits outweigh the potential risks to the foal. [3]
Side Effects
One of the main side effects of SGLT2 inhibitors in horses is hypertriglyceridemia, meaning elevated levels of triglycerides in the bloodstream. When severe, hypertriglyceridemia can contribute to liver or kidney dysfunction.
Many horses treated with SGLT2 inhibitors develop mild hypertriglyceridemia while on the medication. In most cases, there is no evidence of liver or kidney dysfunction associated with this change. Hypertriglyceridemia also appears to resolve or become less severe with ongoing treatment. [1]
Although this effect is often mild, monitoring blood triglyceride levels is recommended. Your veterinarian may request routine bloodwork to track changes while your horse is receiving an SGLT2 inhibitor. [1]
Another important side effect is polyuria and polydipsia. Polyuria refers to excessive urination, which can contribute to dehydration. To compensate, some animals become polydipsic, meaning they drink excessively.
Most horses do not show signs of dehydration while taking SGLT2 inhibitors as long as they have free access to water. [1] Your veterinarian may ask you to monitor your horse’s water intake and hydration status during treatment.
Finally, SGLT2 inhibitor use may increase the risk of urinary tract infections because excess glucose in the urine can provide a food source for bacteria. This increased risk has been described in humans, but it has not been reported in horses. [1][2]
Clinical signs of urinary tract irritation in horses may include: [5]
- Frequent urination
- Urine dribbling
- Straining to urinate
- Urinary incontinence
These signs may warrant veterinary evaluation, especially if they are new or persistent.
In small animal species, SGLT2 inhibitor use has been associated with adverse gastrointestinal reactions. These effects have not been reported in horses, but more data is needed. [3]
Overdose
There are no studies specifically investigating SGLT2 inhibitor toxicosis in horses. One study found that doses of canagliflozin up to six times higher than those typically used had no apparent toxic effects in horses. [6]
In rodents and beagles, very high single doses, up to 3000 times a typical equine dose, were also well-tolerated. [1] These findings suggest that SGLT2 inhibitors may have a wide safety margin, but more equine research is still needed.
Contact your veterinarian if you think your horse is having an adverse reaction to any medication, including an SGLT2 inhibitor.
Drug Interactions
Most reported drug interactions involving SGLT2 inhibitors relate to their effects on the kidneys and their potential to cause dehydration. These drugs should be used cautiously with other medications that affect kidney function or water balance, such as: [3]
- Angiotensin-converting enzyme (ACE) inhibitors, such as enalapril
- Antihypertensive agents, such as amlodipine and telmisartan
- Beta-blockers, such as propranolol
- Diuretics, such as furosemide
Non-steroidal anti-inflammatory drugs, such as firocoxib (Equioxx®) or phenylbutazone (bute), should also be used cautiously with SGLT2 inhibitors. In a dehydrated animal, blood flow to the kidneys decreases, which can increase the risk of NSAID-related kidney injury. [3]
Concurrent administration with fluoroquinolone antibiotics, such as marbofloxacin, or selective serotonin reuptake inhibitors, such as fluoxetine (Prozac®), may increase the hypoglycemic effect of an SGLT2 inhibitor. [3]
Regulatory Status & Legal Considerations
There are currently no equine-specific formulations of SGLT2 inhibitors available. As a result, veterinarians prescribe these medications off-label and rely on available research and clinical experience to design a treatment plan.
Off-label prescribing is common in veterinary medicine because drug companies do not test every drug for every species, dosage, or potential application.
However, owners should be aware that many manufacturers do not warranty products used in an off-label manner. This means that if a horse has an adverse reaction, the company may not refund the medication.
Status in Competition
The three main SGLT2 inhibitors, ertugliflozin, velagliflozin, and canagliflozin, are controlled substances in Federation Equestre Internationale competitions. [7] These medications are typically permitted for use out of competition but are banned during competition.
Owners and veterinarians must pay close attention to withdrawal times to ensure the horse is medication-free at the time of competition. Currently, the FEI does not list a specific withdrawal time for SGLT2 inhibitors.
Other competition organizations may handle these drugs differently. Always confirm current medication rules with your governing body before administering any prescription drug to a competing horse.
Frequently Asked Questions
Here are some frequently asked questions about SGLT2 inhibitors in horses:
SGLT2 inhibitors are prescription medications used to help manage diabetes mellitus in humans. In horses, they may be prescribed off-label to manage insulin resistance characteristic of metabolic disease. They may help lower blood glucose in equine cases that do not fully respond to dietary and management changes.
SGLT2 inhibitors have not been well-studied in horses. In humans, they work by blocking sodium-glucose cotransporter 2 proteins in the kidneys. This reduces the amount of glucose reabsorbed back into the bloodstream and resulting in more sugar excretion through urine. By helping lower circulating glucose, these medications may reduce one of the metabolic drivers of laminitis in insulin-dysregulated horses.
SGLT2 inhibitors are used in horses to help control severe insulin dysregulation that has not improved enough with standard management alone. They are most often considered for horses with recurrent or high-risk endocrinopathic laminitis associated with equine metabolic syndrome. In these cases, the goal is not simply to lower blood sugar, but to reduce hyperinsulinemia and support better metabolic control.
SGLT2 inhibitors are not approved for use in horses and are prescribed off-label in equine medicine. This means veterinarians use human drug formulations based on available research and clinical experience rather than an equine-specific approved product. Because of that, treatment should only be started and monitored under veterinary supervision.
The SGLT2 inhibitors most commonly used or discussed in horses include canagliflozin, ertugliflozin, dapagliflozin, and velagliflozin. Of these, canagliflozin and ertugliflozin are the most studied in equine patients. Veterinarians typically prescribe them as oral medications, and some formulations may be compounded into liquids, capsules, or pastes to make dosing easier.
SGLT2 inhibitors are not a replacement for diet and weight management in horses with insulin dysregulation. Nutritional control remains the foundation of treatment, especially a forage-based feeding plan that supports weight control and limits excess sugar intake. These drugs are generally used as an adjunct when diet, exercise, and body condition management are not enough on their own.
SGLT2 inhibitors can begin working in horses within days to weeks, depending on the horse's metabolic status and the severity of disease. Some horses show measurable reductions in insulin and glucose fairly early after starting treatment. Even so, the overall clinical response depends on the full management plan, including diet, hydration, body condition, and laminitis control.
SGLT2 inhibitors can cause side effects in horses, with hypertriglyceridemia being one of the most important concerns. They can also increase urination and drinking, which may raise the risk of dehydration if water intake is not maintained. In theory, there is also an increased risk of urinary tract infection due to excess glucose in the urine. Any abnormal urination behaviors or signs should be taken seriously.
Horses taking SGLT2 inhibitors do need close monitoring because the treatment affects insulin, glucose, hydration, and triglyceride levels. Veterinarians often recommend baseline bloodwork before starting the medication and repeat testing within about 2 to 4 weeks. Owners should also watch for changes in appetite, body condition, drinking, urination, and overall comfort while the horse is on therapy.
You should call the veterinarian if your horse develops reduced appetite, worsening laminitis pain, unusual weight or body condition loss, or signs of dehydration while taking an SGLT2 inhibitor. New urinary changes such as straining, dribbling, incontinence, or marked increases in urination and drinking also warrant prompt attention. These medications are usually used in horses with significant metabolic disease, so early follow-up is important if anything changes.
Horses may not be allowed to compete while taking SGLT2 inhibitors because competition rules can restrict these drugs. The article notes that canagliflozin, ertugliflozin, and velagliflozin are controlled substances in FEI competition and are banned during competition itself. Owners, trainers, and veterinarians should always confirm the current medication rules and withdrawal guidance with the relevant governing body before showing.
Summary
SGLT2 inhibitors are an emerging treatment option for horses with severe insulin dysregulation and endocrinopathic laminitis, particularly when traditional management strategies are not enough.
- These medications work by increasing glucose excretion through the kidneys, which can help lower circulating insulin levels in horses with metabolic disease
- They are used most often in horses and ponies with equine metabolic syndrome
- Canagliflozin and ertugliflozin are the SGLT2 inhibitors most frequently discussed in equine medicine
- SGLT2 inhibitors do not replace proper diet management, weight control, and exercise programs designed to improve metabolic health
- Potential adverse effects include dehydration, excessive urination, hypertriglyceridemia, and possible urinary complications, making regular veterinary monitoring essential during treatment
References
- Menzies-Gow. N. J. and Knowles. E. J. Sodium-Glucose Transport Protein 2 Inhibitor Use in the Management of Insulin Dysregulation in Ponies and Horses. Journal of Veterinary Pharmacology and Therapeutics. 2025.
- Padda. I. S. et al. Sodium-Glucose Transport Protein 2 (SGLT2) Inhibitors. StatPearls. 2024.
- Budde. J. A. et al. Eds. Plumb's Veterinary Drug Handbook. 10th edition. Educational Concepts. 2023.
- Sapra. A. and Bhandari. P. Diabetes. StatPearls. StatPearls Publishing, Treasure Island (FL). 2026.
- Reed. S. M. et al. Equine Internal Medicine. 3rd ed. Saunders Elsevier. 2010.
- Michanek. P. et al. O103 | The Effect of Canagliflozin on Blood Glucose and Insulin in Healthy Standardbred Horses. Journal of Veterinary Pharmacology and Therapeutics. 2023.
- 2026 Prohibited Substances List. FEI. 2026.
