Expanded use of sodium‐glucose cotransporter 2 inhibitors: Evidence beyond heart failure with reduced ejection fraction

Abstract

AbstractFollowing the results observed in the DAPA‐HF trial and subsequent FDA approval of dapagliflozin in patients living with heart failure with reduced ejection fraction (HFrEF), numerous trials quickly began to assess the effects of sodium‐glucose cotransporter 2 inhibitors (SGLT2i) in a wide range of cardiovascular (CV) conditions. Since the publication of those findings, multiple SGLT2i have demonstrated benefit in patients regardless of left ventricular ejection fraction (LVEF)—allowing the drug class to establish itself within the first line of guideline‐directed medication therapy. Although the full mechanistic properties of SGLT2i in heart failure (HF) have yet to be fully understood, benefits in other disease states have continued to emerge over the past decade. This review summarizes the findings of 14 clinical trials investigating the use of SGLT2i in various CV disease states, with a special focus on HF with preserved ejection fraction (HFpEF) and acute decompensated HF (ADHF). Additionally, studies assessing the CV‐related mechanisms, cost‐effectiveness, and exploratory effects of dual SGLT1/2 blockade are described. A review of select ongoing trials has also been incorporated to further characterize the research landscape with this medication class. The aim of this review is to serve as a comprehensive tool for healthcare providers to better understand how this class of diabetes medications established its place in the treatment of HF.