Effect of Fenofibrate on Markers of Gut Barrier Function in Dogs With Naturally Occurring Diabetes Mellitus

J Vet Intern Med. 2025 May-Jun;39(3):e70125. doi: 10.1111/jvim.70125.

Abstract

Background: Fenofibrate improves gut barrier function and reduces serum lipids in purpose-bred dogs with induced diabetes mellitus (DM), but its effects in dogs with naturally occurring DM are unknown.

Objectives: Determine the effects of fenofibrate on markers of systemic and pancreatic inflammation, markers of gut barrier function, lipoprotein profiles, and glycemic control in dogs with naturally occurring DM.

Animals: Sixteen client-owned dogs with naturally occurring, uncomplicated DM.

Methods: Longitudinal cohort study. Dogs were treated with fenofibrate (Tricor, 6-10 mg/kg, P.O., once daily) for 21 days. Interstitial glucose, serum cytokines, lipopolysaccharide (LPS), pancreatic lipase, and lipid profiles were compared between baseline and day 21 using paired t-tests and Wilcoxon signed-rank tests.

Results: Fenofibrate had no effect on glycemic control, serum cytokines, or serum pancreatic lipase. Compared to baseline, the concentrations of serum LPS decreased at day 21 by (mean ± SD) 15 ± 24% (95% CI 2-28%, p = 0.03), serum triglycerides decreased by 36 ± 39% (95% CI 15-56%, p = 0.002), and serum cholesterol decreased by 20 ± 14% (95% CI 12-28%, p < 0.0001).

Conclusions and clinical importance: Fenofibrate treatment was not associated with a decrease in markers of systemic or pancreatic inflammation. In diabetic dogs, short-term fenofibrate treatment appears to be safe, and the improvement in gut barrier function and lipid profiles might lead to long-term benefits, such as reduction in pancreatitis risk and frequency of signs of gastrointestinal disease.

Keywords: fibroblast growth factor‐21; lipopolysaccharide; pancreatic lipase immunoreactivity; pancreatitis; peroxisome proliferator‐activated receptor.

MeSH terms

  • Animals
  • Biomarkers / blood
  • Blood Glucose / analysis
  • Cytokines / blood
  • Diabetes Mellitus* / blood
  • Diabetes Mellitus* / drug therapy
  • Diabetes Mellitus* / veterinary
  • Dog Diseases* / blood
  • Dog Diseases* / drug therapy
  • Dogs
  • Female
  • Fenofibrate* / pharmacology
  • Fenofibrate* / therapeutic use
  • Hypolipidemic Agents* / pharmacology
  • Hypolipidemic Agents* / therapeutic use
  • Lipase / blood
  • Lipopolysaccharides / blood
  • Longitudinal Studies
  • Male

Substances

  • Fenofibrate
  • Biomarkers
  • Hypolipidemic Agents
  • Blood Glucose
  • Cytokines
  • Lipase
  • Lipopolysaccharides