O'Kell_2025_J.Vet.Intern.Med_39_e70125

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.