Evaluation of dose-dependent effects of dapagliflozin on urinary glucose and plasma ketone bodies in healthy dogs.

Dapagliflozin at 1.0 mg/kg induces significant ketogenesis and diuresis in healthy dogs, warranting caution at higher doses.

This randomized, placebo-controlled crossover pharmacodynamic study evaluated the dose-dependent effects of single oral doses of dapagliflozin (0.1, 0.3, and 1.0 mg/kg) in five healthy Beagle dogs, with 14-day washout intervals between treatments. Dapagliflozin is a sodium-glucose cotransporter-2 (SGLT2) inhibitor increasingly of interest in veterinary cardiology due to its proven benefits in human heart failure patients. The study measured urinary glucose excretion, plasma ketone bodies, urine volume, and electrolyte concentrations across multiple time points over 24 hours. Key findings demonstrated that 24-hour urinary glucose excretion was significantly greater at 0.3 mg/kg compared to 0.1 mg/kg, but no additional significant increase was observed at 1.0 mg/kg, suggesting a plateau effect on glucosuria between 0.3 and 1.0 mg/kg. Importantly, the 1.0 mg/kg dose significantly elevated plasma ketone body concentrations from 4 to 24 hours post-administration compared to placebo, raising concerns about ketogenesis at higher doses. Additionally, the 1.0 mg/kg group exhibited significantly greater urine output during the first 6 hours, confirming a diuretic effect at this dose. No significant electrolyte disturbances were reported. While these findings suggest that 0.3 mg/kg may provide adequate glucosuria with a potentially safer ketogenic profile than 1.0 mg/kg, the authors caution that extrapolation to dogs with heart failure requires further investigation, as disease state may substantially alter pharmacodynamic responses.

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