What is the current evidence for using dapagliflozin or other SGLT2 inhibitors in dogs with cardiac disease?

Question

Accepted Answer

Dapagliflozin is the most promising sodium-glucose cotransporter 2 (SGLT2) inhibitor candidate for canine cardiac disease, identified through pharmacology, safety, and pharmacokinetic review of regulatory documentation for empagliflozin, canagliflozin, and dapagliflozin in dogs.2 The primary cardiac indication under investigation is myxomatous mitral valve disease (MMVD), the most prevalent cause of chronic heart failure in dogs.2 Standard-of-care with pimobendan and loop diuretics leaves MMVD with a poor prognosis due to its progressive nature, which is the clinical gap SGLT2 inhibitors are being evaluated to address.2 The parallels between canine MMVD and human chronic heart failure — for which dapagliflozin is already approved — form the translational rationale.2 In healthy dogs, a single oral dose of dapagliflozin at 1.0 mg/kg produces both diuretic and ketogenic effects, supporting its potential decongestive and metabolic utility in heart failure.1 Plasma ketone body concentrations became significantly higher at the 1.0 mg/kg dose compared to placebo beginning at 4 hours post-administration.1 Under normal fasting conditions, canine plasma β-hydroxybutyrate is approximately 100 μmol/L (range 0–400 μmol/L); the concentration thought to confer myocardial metabolic benefit in prior work ranges from 500 to 3,000 μmol/L, though the threshold has not been established in dogs.1 At 1.0 mg/kg, only 1 of 5 dogs exceeded 500 μmol/L, so whether this dose reliably achieves therapeutically relevant ketone concentrations in cardiac patients remains unresolved.1 The diuretic benefit of dapagliflozin in canine heart failure is uncertain. Whether glucosuria-driven osmotic diuresis translates into meaningful decongestion in dogs with heart failure has not been established, and the physiological response in cardiac patients may differ from healthy dogs due to altered renin-angiotensin-aldosterone system activation and differences in fluid distribution.1 A clinically relevant advers