Can a diabetes drug help dogs with heart disease?

A prospective study in the Journal of Veterinary Internal Medicine evaluated the sodium-glucose transporter 2 (SGLT2) inhibitor dapagliflozin in dogs with heart disease and found that short-term treatment was well tolerated, resulting in marked glycosuria, but did not significantly increase urinary sodium excretion. The findings suggest that, in dogs, any cardiovascular benefit from this drug class may stem from mechanisms beyond natriuresis alone.¹

This matters because SGLT2 inhibitors have become important drugs in human cardiovascular medicine, where they are linked not only to glucose-lowering effects but also to improved heart failure outcomes. In humans, several proposed mechanisms have been studied, including natriuresis, altered substrate utilization, and anti-inflammatory or antioxidative effects. This veterinary study was designed to see whether similar physiologic signals could be detected in dogs with heart disease.¹

The investigators enrolled 11 client-owned dogs with heart disease, and 10 completed the study. The dogs had a range of cardiac diagnoses, most commonly myxomatous mitral valve disease. The study was prospective, multicenter, open-label, and uncontrolled. Dogs received once-daily oral dapagliflozin at approximately 0.45 to 1.0 mg/kg/day, and blood and urine biomarkers were reassessed after 5 to 7 days.¹

The main result was that urine glucose increased dramatically after treatment, which was the expected pharmacologic effect of an SGLT2 inhibitor. However, urine sodium did not change significantly, and fractional excretion of sodium did not increase. In other words, the drug behaved like an SGLT2 inhibitor should in terms of glucosuria, but the study did not support a short-term natriuretic effect in this population.¹

The biomarker data were especially interesting. Serum total thiol concentration increased, which the authors interpreted as a possible signal of antioxidative activity. Haptoglobin also changed significantly, whereas other inflammatory and oxidative markers did not show clear treatment effects. The authors suggested that any future cardiac benefit from SGLT2 inhibition in dogs may involve anti-inflammatory, antioxidative, or metabolic pathways rather than simple diuresis.¹

Safety was reassuring in this small cohort. Serious adverse effects, such as hypoglycemia or ketoacidosis, were not observed. One dog was withdrawn after diarrhea following the first dose, and another developed pollakiuria and stranguria after the study ended, which resolved with empiric antibiotic treatment. No meaningful changes in quality of life were detected during the short study window.¹

For veterinary clinicians, the practical takeaway is that dapagliflozin appears promising as a well-tolerated investigational option in dogs with heart disease, but the short-term data do not yet support assuming a natriuretic mechanism the way many clinicians might from human literature. The paper is hypothesis-generating rather than practice-changing, and larger controlled trials will be needed to determine which cardiac patients might benefit, what the optimal dose is, and whether biomarker changes translate into clinical outcomes.¹

Reference

1. Massey LK, Ward JL, Crooks AV, et al. Effect of the sodium glucose transporter-2 inhibitor dapagliflozin on urine and blood biomarkers in dogs with heart disease. J Vet Intern Med. 2026;40(2):aalag036. doi:10.1093/jvimsj/aalag036