Effect of Phenylbutazone Administration on Insulin Sensitivity in Horses With Insulin Dysregulation.
Abstract: Phenylbutazone is prescribed to manage pain caused by hyperinsulinemia-associated laminitis. Phenylbutazone reduces glucose and insulin concentrations in horses with insulin dysregulation (ID) but the underlying mechanism of action is unknown. Objective: Investigate the effect of phenylbutazone on tissue insulin sensitivity in horses. It is hypothesized that the reduced glucose and insulin concentrations in horses with ID receiving phenylbutazone are mediated by a higher tissue insulin sensitivity. Methods: Fifteen light breed horses, including seven with ID. Methods: Randomized cross-over study. Horses underwent a modified frequently sampled intravenous glucose tolerance test (mFSIGTT) after 8 days of treatment with phenylbutazone (4.4 mg/kg IV daily) or placebo (5 mL 0.9% saline IV daily). After a 10-day washout period, horses received the alternative treatment for 8 days and a second mFSIGTT. Minimal model analysis was performed, and the effects of ID status and phenylbutazone were investigated with p < 0.05 considered significant. Results: In horses with ID, phenylbutazone increased tissue insulin sensitivity index (median [interquartile range]: 0.39 [0.14-0.74] vs. 0.56 [0.55-1.18] ×10-4 L/mIU/min, p = 0.03), and decreased glucose (21 726 [19 040-24 948] vs. 22 909 [22 496-26 166] mg/dL × min, p = 0.02) and insulin (19 595 [16 147-29 698] vs. 22 752 [20 578-31 826] μIU/mL × min, p = 0.03) areas under the curves. No effect was detected in horses administered placebo. Conclusions: Phenylbutazone reduces insulin concentration in horses with ID by modulating tissue insulin sensitivity, suggesting that its relevance in the management of ID can extend beyond laminitis-associated pain.
© 2025 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.
Publication Date: 2025-02-27 PubMed ID: 40011055PubMed Central: PMC11864851DOI: 10.1111/jvim.70028Google Scholar: Lookup
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Summary
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This research explores the effects of a pain-relieving drug, Phenylbutazone, on insulin sensitivity in horses, finding that it increases tissue insulin sensitivity and lowers glucose and insulin levels in horses with insulin dysregulation.
Objective
- The study aimed to investigate the effect of the drug Phenylbutazone on tissue insulin sensitivity in horses. This was driven by the observation that in horses experiencing insulin dysregulation (ID), Phenylbutazone was seen to decrease glucose and insulin concentrations, though the mechanisms behind this were previously unknown. The researchers hypothesized that Phenylbutazone might work by enhancing tissue insulin sensitivity.
Methodology
- Fifteen horses of a light breed were selected, among which seven had insulin dysregulation.
- In a randomized cross-over study, the horses were subjected to a modified frequently sampled intravenous glucose tolerance test (mFSIGTT) after being treated with either Phenylbutazone or a placebo for eight days.
- Following a washout period of 10 days, the horses were then treated with the alternative substance for 8 days before undergoing a second mFSIGTT.
- The data gained from the test was analysed using minimal model analysis, seeking any significant effects (p < 0.05) on the ID status of the horses and the usage of Phenylbutazone.
Results
- In horses with ID, Phenylbutazone increased the tissue insulin sensitivity index and reduced the areas under the curves for both glucose and insulin.
- These effects were not detected in horses that had been administered the placebo.
Conclusions
- The study concluded that Phenylbutazone works to reduce insulin concentration in horses with insulin dysregulation through a modulation of tissue insulin sensitivity. This supposes that the drug’s importance in managing insulin dysregulation goes beyond its established use in reducing pain associated with laminitis, a disease often associated with hyperinsulinemia.
Cite This Article
APA
Kemp KL, Yuen NKY, Skinner JE, Bertin FR.
(2025).
Effect of Phenylbutazone Administration on Insulin Sensitivity in Horses With Insulin Dysregulation.
J Vet Intern Med, 39(2), e70028.
https://doi.org/10.1111/jvim.70028 Publication
Researcher Affiliations
- School of Veterinary Science, The University of Queensland, Gatton, Queensland, Australia.
- School of Veterinary Science, The University of Queensland, Gatton, Queensland, Australia.
- Elizabeth Macarthur Agricultural Institute, Department of Primary Industries, Menangle, New South Wales, Australia.
- School of Agriculture and Environmental Science, University of Southern Queensland, Queensland, Australia.
- School of Veterinary Science, The University of Queensland, Gatton, Queensland, Australia.
- College of Veterinary Medicine, Department of Veterinary Clinical Sciences, Purdue University, West Lafayette, Indiana, USA.
MeSH Terms
- Animals
- Horses
- Phenylbutazone / therapeutic use
- Phenylbutazone / administration & dosage
- Phenylbutazone / pharmacology
- Insulin Resistance / physiology
- Horse Diseases / drug therapy
- Horse Diseases / metabolism
- Cross-Over Studies
- Female
- Insulin / blood
- Male
- Glucose Tolerance Test / veterinary
- Blood Glucose / analysis
- Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
- Anti-Inflammatory Agents, Non-Steroidal / pharmacology
- Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
Grant Funding
- The University of Queensland Graduate School Research Training Program Scholarship
- The University of Queensland Destination Australia Scholarship
- D19-EQ-302 / Morris Animal Foundation
Conflict of Interest Statement
Authors declare no off‐label use of antimicrobials. The authors declare no conflicts of interest.
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