Equine Internal Medicine Resident The Ohio State University Columbus, Ohio, United States
Abstract: Background– Equine metabolic syndrome (EMS) and insulin dysregulation (ID) are widely recognized conditions associated with hyperinsulinemia and laminitis. Metformin and sodium-glucose cotransporter-2 inhibitors (SGLT2i) are each used extensively to manage equine ID. Combination therapy with both drugs improves glycemic control in diabetic humans; however, combined administration of an SGLT2i and metformin has not been evaluated in horses.
Hypothesis/Objectives– When used in combination, canagliflozin and metformin will improve insulin and glucose dynamics in an additive (or synergistic) fashion in equine ID, improving clinical endocrinological outcomes compared to administration of canagliflozin alone.
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 (0.3 mg/kg PO q24h) + metformin (30 mg/kg PO q12h), and placebo. Horses were subjected to an oral sugar test (OST) and insulin tolerance test (ITT) before and after 7 days of their respective treatment, and results were compared within (pre and post) and between groups.
Results– Combination treatment resulted in greater attenuation of post-OST insulin concentrations than canagliflozin monotherapy (P = 0.05). Horses receiving canagliflozin as monotherapy or combination therapy showed a decreased glycemic response during an ITT compared to horses receiving placebo (P = 0.02).
Conclusions and Clinical Importance– Treatment with canagliflozin and metformin improved some aspects of insulin and glucose dynamics compared to canagliflozin monotherapy. Administration of canagliflozin was associated with decreased tissue insulin sensitivity in response to an ITT. Combination therapy with canagliflozin and metformin may improve management of equine ID.
