Effect of the sodium glucose transporter-2 inhibitor dapagliflozin on urine and blood biomarkers in dogs with heart disease.

Abstract

BACKGROUND: Sodium-glucose transport 2 inhibitors (SGLT2i) decrease morbidity and mortality in human patients with heart failure through a variety of proposed mechanisms, including natriuresis and glucosuria. The effects of SGLT2i on urine sodium (uNa) and urine glucose (uGlu) concentrations in dogs with heart disease have not been evaluated. HYPOTHESIS/OBJECTIVES: Administration of the SGLT2i dapagliflozin to dogs with heart disease will be well-tolerated and increase uNa and uGlu concentrations. Laboratory results and biomarker assays will provide insight into potential mechanisms of action. ANIMALS: Ten client-owned dogs with heart disease with or without congestive heart failure. METHODS: Prospective multicenter open-label uncontrolled study. Blood and urine biochemistry and oxidative and inflammatory biomarkers were evaluated at baseline and 5-7 days after 0.45-1 mg/kg/day PO dapagliflozin. RESULTS: A treatment effect was observed for uGlu (baseline, 14 mg/dL; IQR, 2-19 mg/dL; treatment effect +3102 mg/dL; IQR, 2390-4387 mg/dL; P = .002) but not for uNa (baseline, 75 mmol/L; IQR, 28-129 mmol/L; treatment effect, -41 mmol/L; IQR, -96-21 mmol/L; P = .12). Serum total thiol concentration increased (baseline, 145 μmol/L; SD, 32 μmol/L; treatment effect, +7 μmol/L; SD, 9 μmol/L; P = .04), suggesting an antioxidative effect. Serious adverse effects, including hypoglycemia or ketoacidosis, were not observed. CONCLUSIONS AND CLINICAL IMPORTANCE: Short-term PO dapagliflozin was well-tolerated and associated with glucosuria but not natriuresis. Clinical benefit of SGLT2i in dogs with heart disease might include non-natriuretic mechanisms, such as anti-inflammatory, antioxidative, or metabolic effects.