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Canagliflozin treatment of a horse with hyperinsulinemia, including pharmacokinetic analysis of different dosing protocols: a case report.
Abstract: Laminitis is a complex and painful disease of the equine foot. Insulin dysregulation (ID) resulting in hyperinsulinemia is responsible for more than 90% of cases in the general horse and pony population. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a relatively new class of drug that has gained considerable popularity as an off-label treatment of hyperinsulinemia-associated laminitis (HAL) in horses when traditional management changes and treatments are unsuccessful. In Canada, canagliflozin is the SGLT2i most available to equine veterinarians; although no dosing protocols have been well-validated in horses, it is commonly administered orally at 0.6 mg/kg once daily. However, due to its long half-life in the horse, we hypothesized that every other day (EOD) dosing might be efficacious. Here we report the clinical outcome and pharmacokinetics of once daily versus EOD canagliflozin in a teaching horse with hyperinsulinemia and a history of severe laminitis. We found that insulin levels in this patient could be maintained within normal limits using EOD oral treatment of canagliflozin at a dose of 0.6 mg/kg. Daily dosing of canagliflozin led to accumulation resulting in approximately three times the drug exposure achieved with EOD dosing, where no accumulation was observed. Maximum plasma concentrations were 934.2 ng/mL after 30 days of single daily dosing and 324.3 ng/mL after 30 days of EOD dosing. This may be a promising new dosing strategy, although prospective trials in risk-matched populations are needed to assess the incidence of medication-associated adverse events and laminitis to determine the safety profiles of canagliflozin dosing strategies.
Copyright © 2026 Burbidge, White, Armstrong and Rosa.
Publication Date: 2026-07-13 PubMed ID: 42516305PubMed Central: PMC13402110DOI: 10.3389/fvets.2026.1838222Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
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Summary
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Overview
- This research article reports on the treatment of a horse with hyperinsulinemia-linked laminitis using canagliflozin, analyzes the pharmacokinetics of different dosing protocols, and suggests that every-other-day dosing might maintain effective insulin control with less drug accumulation than daily dosing.
Background and Significance
- Laminitis in Horses: Laminitis is a painful and complex condition affecting the feet of horses, often leading to inflammation and severe lameness.
- Role of Insulin Dysregulation (ID): Over 90% of laminitis cases are associated with hyperinsulinemia, a condition where there is excessive insulin in the bloodstream, often due to insulin dysregulation.
- Treatment Challenges: Traditional management and therapies may be ineffective in controlling hyperinsulinemia-associated laminitis (HAL), necessitating alternative treatment options.
Introduction to Canagliflozin and Its Use
- Canagliflozin: This drug is a sodium-glucose cotransporter 2 inhibitor (SGLT2i) originally used to lower blood sugar by promoting glucose excretion via the kidneys.
- Off-Label Use in Horses: Canagliflozin has gained popularity among equine veterinarians in Canada for treating HAL when other treatments fail, though there are no well-established dosing protocols for horses.
- Common Dosing: Typically administered orally at 0.6 mg/kg once daily in horses.
Study Purpose and Hypothesis
- Problem: Canagliflozin has a long half-life in horses, which could lead to drug accumulation with daily dosing, potentially increasing risk of side effects.
- Hypothesis: Every-other-day (EOD) dosing might control insulin levels effectively while reducing drug accumulation.
- Study Goal: To report the clinical outcome and pharmacokinetics of once daily vs. EOD canagliflozin in a horse with hyperinsulinemia and severe laminitis history.
Methods
- The study was a case report involving a teaching horse exhibiting hyperinsulinemia and prior severe laminitis.
- Canagliflozin was administered orally in two phases: first once daily, then every other day, both at 0.6 mg/kg.
- Pharmacokinetic analyses were conducted to measure drug plasma concentrations and evaluate accumulation.
- Monitoring of insulin levels was performed to assess therapeutic effectiveness.
Key Findings
- Insulin Control: EOD dosing of canagliflozin was sufficient to maintain insulin levels within normal limits in the horse.
- Drug Accumulation: Daily dosing led to significant drug accumulation (about threefold increase in exposure), indicated by higher plasma concentrations compared to EOD dosing.
- Pharmacokinetic Values:
- After 30 days of daily dosing, maximum plasma concentration (Cmax) was 934.2 ng/mL.
- After 30 days of EOD dosing, maximum plasma concentration was much lower at 324.3 ng/mL.
- EOD Dosing Advantage: No accumulation was seen with EOD dosing, potentially reducing risks related to drug build-up.
Implications and Recommendations
- The results suggest that canagliflozin administered every other day may be an effective and safer alternative to daily dosing in managing hyperinsulinemia in horses with laminitis.
- Because this was a single-case report, broad conclusions cannot be drawn without further research.
- There is a need for prospective, controlled clinical trials in horses at risk to:
- Confirm the effectiveness and safety of EOD canagliflozin dosing.
- Determine the incidence of any medication-related adverse events.
- Assess laminitis outcomes associated with various dosing schedules.
- Such research would help establish validated, evidence-based dosing protocols for veterinarians treating HAL.
Cite This Article
APA
Burbidge C, White K, Armstrong K, Rosa B.
(2026).
Canagliflozin treatment of a horse with hyperinsulinemia, including pharmacokinetic analysis of different dosing protocols: a case report.
Front Vet Sci, 13, 1838222.
https://doi.org/10.3389/fvets.2026.1838222 Publication
Researcher Affiliations
- Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada.
- Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada.
- Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada.
- Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada.
Conflict of Interest Statement
The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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