Sodium-Glucose Co-Transporter 2 Inhibitors and Insights from Biomarker Measurement in Heart Failure Patients

BACKGROUND: Several large trials have demonstrated cardiac benefits in patients with and without established cardiovascular disease treated with sodium-glucose co-transporter 2 inhibitors (SGLT2i). Most recently, in patients with heart failure with reduced ejection fraction (HFrEF), the risk of worsening HF or cardiovascular death was lower among those who received dapagliflozin than among those who received placebo, regardless of the presence or absence of diabetes. Biomarkers may provide insight into understanding the mechanism of cardiovascular benefit observed in patients receiving SLGT2i. Several mechanisms have been proposed, including improvement in ventricular unloading due to the natriuretic effects, afterload reduction via reduction in blood pressure and improvement in vascular function, improvement in cardiac metabolism and bioenergetics, and reduction in cardiac fibrosis and necrosis, among others. CONTENT: We discuss several animal and human studies on the effect of SGLT2i on various biomarkers. Modest reduction or blunting of rise over time in concentrations of atrial natriuretic peptide, B-type natriuretic peptide, and N-terminal pro B-type natriuretic peptide and reduction in high-sensitivity troponin has been observed in patients receiving SLGT2i. Concentrations of biomarkers such as sST2 and galectin-3 have been unchanged whereas inflammatory markers such as fibronectin 1, interleukin-6, matrix metalloproteinase 7, and tumor necrosis factor-1 are decreased with SGLT2i therapy. SUMMARY: The effect of SLGT2i on various circulating biomarkers allows insight into the understanding of mechanisms of cardiovascular benefits with SGLT2i use. Further studies are needed to understand such mechanisms and to understand how biomarkers can be used for risk prediction and personalization of care in patients receiving SLGT2i.