The Evolution of Sodium-Glucose Co-Transporter-2 Inhibitors in Heart Failure

Sodium-glucose co-transporter-2 (SGLT2) inhibitors have evolved over the years based on data from several randomized double-blinded placebo-controlled clinical trials from being used primarily for blood sugar control in patients with diabetes to being used in all patients with heart failure with reduced ejection fraction (HFrEF) to decrease the risk of hospitalization for heart failure (HF) or death from cardiovascular (CV) causes. They have also been shown to slow the progression of renal disease and prevent death related to renal causes in patients with chronic kidney disease (CKD). More recently, they are currently being studied to decrease the risk of HF hospitalization in patients with the preserved ejection fraction subtype of HF and have shown positive results. The transition of SGLT2 from a medication used in diabetes to an established HF medication was a result of the hypothesis generated from the analysis of earlier trials in diabetic patients and further testing of this hypothesis in an HF population. Our distinctive approach in this review is to highlight with greater details in a time-dependent fashion the rationale for the paradigm shift of SGLT2 inhibitors from their use in diabetic patients initially for blood sugar control to their recommendation in all patients with HF regardless of the presence of diabetes by detailing the results of several major clinical trials and a meta-analysis study that led to this discovery and clinical indication. We would also highlight the key properties in detail of seven crucial clinical trials involving SGLT2 inhibitors.