Equine Internal Medicine Resident The Ohio State University Columbus, Ohio, United States
Abstract: Background – Equine metabolic syndrome (EMS) and insulin dysregulation (ID) are frequently managed using metformin and sodium-glucose cotransporter-2 inhibitors (SGLT2i) given individually. Adverse effects of SGLT2i administration in horses include hypertriglyceridemia, which has been linked to hepatopathy in equids. Metformin can modulate SGLT2i-associated hypertriglyceridemia in humans, but this protective effect has not been investigated in equids.
Hypothesis/Objectives – To evaluate 1) the effects of short-term canagliflozin administration on triglyceride concentrations and biomarkers of hepatic disease and 2) the influence of co-administration with metformin on these outcomes.
Animals – Seventeen adult, light breed horses with naturally-occurring ID.
Methods – Horses were randomly assigned to one of three groups: canagliflozin (0.3 mg/kg PO q24h), canagliflozin (0.3mg/kg PO q24h) + metformin (30 mg/kg PO q12h), and placebo. Serial triglyceride concentrations and serum biochemistry profiles were performed before, during, and after a 7-day treatment course.
Results – Triglyceride concentrations increased in all horses receiving canagliflozin (P = 0.03), and this effect was not attenuated by metformin. Serum ALP concentrations were higher in horses receiving canagliflozin alone (P = 0.04), but serum SDH, GGT, and ALT concentrations were not affected by treatment.
Conclusions and Clinical Importance – The addition of metformin did not prevent canagliflozin-associated hypertriglyceridemia in horses with ID. However, combination treatment significantly affected ALP concentrations and therefore may be beneficial in this population. Given the widespread clinical use of these drugs, further studies incorporating longer therapeutic intervals are warranted to evaluate the utility of these medications for horses with metabolic disease.
