Background: Non-steroidal anti-inflammatory drugs (NSAIDs) have been reported to increase insulin secretion in patients with diabetes. Horses with insulin dysregulation (ID) often receive phenylbutazone to manage the pain of hyperinsulinemia-associated laminitis (HAL). Hypothesis/
Objectives: Investigate the effects of phenylbutazone on insulin and glucose dynamics in horses with ID. Animals: 16 light breed horses, including 7 with ID.
Methods: In a randomised crossover trial, horses received phenylbutazone (4.4 mg/kg IV daily) or placebo, with a 10-day washout period between treatments. On day 8 of treatment a modified frequently sampled intravenous glucose tolerance test (mFSIGTT) was performed and on day 9 an oral glucose test (OGT). Insulin, glucose, and incretin concentrations were measured. Paired t-tests or Wilcoxon signed-rank test were used, with P < .05 considered significant.
Results: In horses with ID, phenylbutazone significantly decreased both glucose area under the curve (AUC; 1198 ± 224.5 vs. 1412 ± 182.6 mmol/L x min, phenylbutazone vs. placebo; P = .01) and insulin AUC (17710 ± 6676 vs. 22930 ± 8788 µIU/mL x min, phenylbutazone vs. placebo; P = .03) during the OGT. There was no significant effect of phenylbutazone treatment on incretins during the OGT. Phenylbutazone improved the tissue insulin sensitivity index (0.56 [0.55 – 1.18] vs. 0.39 [0.14 – 0.74] x10-4L/mU/min, phenylbutazone vs. placebo, P = .03) during the mFSIGTT. No significant effect was observed in control horses.Conclusions and clinical importance: Phenylbutazone improves insulin sensitivity resulting in a decreased insulin secretion, making NSAIDs an attractive pathway for investigation in the management of HAL.
