Short-term clinical responses in horses and ponies treated with canagliflozin: A clinical field study.

Abstract

BACKGROUND: Treatment with the sodium-glucose co-transporter 2 (SGLT2) inhibitor canagliflozin in insulin dysregulated (ID) horses has shown promising results in randomised clinical trials. Larger field studies are needed to further evaluate treatment responses and potential adverse effects under real-world conditions. OBJECTIVES: To assess the short-term effects of canagliflozin on postprandial glucose and insulin responses in client-owned horses and ponies with ID using a single-sample feed-challenge test (FCT), and to characterise treatment-associated changes in bodyweight, liver enzyme activities, and triglyceride concentrations. STUDY DESIGN: Multicentre pre-post intervention study. METHODS: Seventy privately owned horses and ponies with ID, confirmed by an oral sugar test, were enrolled. Horses received oral canagliflozin (0.4-0.6&#x2009;mg/kg bwt once daily) for 3&#x2009;weeks. Bodyweight, clinical biochemical parameters, and glucose and insulin concentrations from an FCT based on each horse's forage were obtained before and after treatment. Data were analysed using linear mixed-effects models. RESULTS: The least squares (LS) means insulin concentrations (&#xb1; SEM) during the FCT decreased from 304.4&#x2009;&#xb1;&#x2009;25.4 to 171.2&#x2009;&#xb1;&#x2009;25.9 &#x3bc;IU/mL after 3&#x2009;weeks of treatment with canagliflozin (p&#x2009;<&#x2009;0.001). Thirteen percent (9/70) of horses did not exhibit a reduction in insulin concentrations after treatment. The geometric LS means (95% confidence interval) triglyceride concentration (0.4 [0.3-0.5] vs. 1.2 [0.9-1.5] mmol/L; p&#x2009;<&#x2009;0.001) and glutamate dehydrogenase (GLDH) activity (91 [73-112] vs. 152 [123-188] &#x3bc;kat/L; p&#x2009;<&#x2009;0.001) increased with treatment. Hyperlipaemia-range triglyceride concentrations (>5.6&#x2009;mmol/L) were observed in 9% (6/70) of treated horses. MAIN LIMITATIONS: Absence of a placebo-treated control group. CONCLUSIONS: The postprandial insulin concentrations decreased in most canagliflozin treated horses, however, a subset failed to respond or developed marked increases in triglycerides. These findings underscore the need for careful monitoring of insulin response and lipid parameters during SGLT2 inhibitor therapy in horses.