Effect of phenylbutazone on insulin levels in horses with insulin dysregulation

The effect was not small, with an approximately 20% reduction in glucose and insulin levels using low to moderate doses of bute. The mechanism of action should be investigated, as well as whether even lower doses might be effective. At this dose, it is hard to see bute being used as a long-term treatment of metabolic syndrome in horses but it adds support to its use during laminitis episodes. I have preferred NSAIDs with a better toxic to therapeutic range, but this gives me pause, at least for the short term.
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Effect of phenylbutazone on insulin secretion in horses with insulin dysregulation
J Vet Intern Med. 2024 Feb 16. doi: 10.1111/jvim.17013. Online ahead of print.
Authors
Kate L Kemp 1 , Jazmine E Skinner 2 , François-René Bertin 1 3
Affiliations

1 School of Veterinary Science, The University of Queensland, Gatton, Queensland, Australia.
2 School of Agriculture and Environmental Science, University of Southern Queensland, Darling Heights, Queensland, Australia.
3 College of Veterinary Medicine, Purdue University, West-Lafayette, Indiana, USA.

PMID: 38363029
DOI: 10.1111/jvim.17013

Abstract

Background: Phenylbutazone is often prescribed to manage pain caused by hyperinsulinemia-associated laminitis, but in diabetic people nonsteroidal anti-inflammatory drugs increase insulin secretion and pancreatic activity.

Hypothesis/objectives: Investigate the effect of phenylbutazone administration on insulin secretion in horses. It was hypothesized that phenylbutazone will increase insulin secretion in horses with insulin dysregulation (ID).

Animals: Sixteen light breed horses, including 7 with ID.

Methods: Randomized cross-over study design. Horses underwent an oral glucose test (OGT) after 9 days of treatment with phenylbutazone (4.4 mg/kg IV q24h) or placebo (5 mL 0.9% saline). After a 10-day washout period, horses received the alternative treatment, and a second OGT was performed. Insulin and glucose responses were compared between groups (ID or controls) and treatments using paired t test and analyses of variance with P < .05 considered significant. Results: In horses with ID, phenylbutazone treatment significantly decreased glucose concentration (P = .02), glucose area under the curve (2429 ± 501.5 vs 2847 ± 486.1 mmol/L × min, P = .02), insulin concentration (P = .03) and insulin area under the curve (17 710 ± 6676 vs 22 930 ± 8788 μIU/mL × min, P = .03) in response to an OGT. No significant effect was detected in control horses. Conclusion and clinical importance: Phenylbutazone administration in horses with ID decreases glucose and insulin concentrations in response to an OGT warranting further investigation of a therapeutic potential of phenylbutazone in the management of hyperinsulinemia-associated laminitis beyond analgesia. Keywords: endocrinology; equine metabolic syndrome; hyperinsulinemia; laminitis; nonsteroidal anti-inflammatory drugs; obesity; oral glucose test. © 2024 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.