Sodium-glucose co-transporter 2 inhibitors: prospects for canine myxomatous mitral valve disease and finding the “right drug” and the “right dose” for dogs

Abstract

Human pharmaceuticals are widely used in veterinary medicine. Nevertheless, identifying the optimal pharmaceuticals and dosages has been a significant challenge, as these medications may not be efficacious or may even be toxic to small animals. Following the approval of a pharmaceutical for human use, comprehensive non-clinical information is made public in Japan as Summary Technical Documentation (STED) and in the U.S. as Drug Approval Packages. As canines are often employed in non-clinical investigations, the information could prove invaluable in identifying the optimal pharmaceuticals and dosages. Sodium-glucose co-transporter 2 (SGLT2) inhibitors represent a class of anti-diabetic agents for humans, with a total of nine drugs currently approved in Japan, the U.S. and the E.U. Among them, dapagliflozin and empagliflozin have been approved for the treatment of chronic heart failure. In canines, myxomatous mitral valve disease (MMVD) represents the most prevalent etiology of chronic heart failure. Despite the recommendation of pimobendan and loop diuretics as standard-of-care medications, MMVD remains a disease with a poor prognosis due to its progressive nature. We examined the pharmacology, safety, and pharmacokinetics of the globally approved SGLT2 inhibitors (empagliflozin, canagliflozin, and dapagliflozin) in canines in the STED. Based on these results, we propose dapagliflozin as the most favorable pharmaceutical in canines. We also discuss the potential effects of SGLT2 inhibitors on canine MMVD, considering the similarities between canine MMVD and human chronic heart failure.