Supplementary Material for: Roles for SGLT2 Inhibitors in Cardiorenal Disease

Cardiovascular disease (CVD) and chronic kidney disease (CKD) share common risk factors, including type 2 diabetes mellitus (T2DM). In cardiovascular outcome studies of patients with T2DM, sodium-glucose cotransporter 2 inhibitor (SGLT2i) therapy was associated with risk reductions in cardiorenal endpoints. This article aims to provide a comprehensive overview of the efficacy of SGLT2i therapy in patients at risk of cardiorenal disease. A literature review of large outcome studies of patients who had CKD or heart failure with reduced ejection fraction (HFrEF, defined as having a left ventricle ejection fraction [LVEF] <40%) or heart failure with preserved ejection fraction (LVEF ≥50%) was undertaken to evaluate the associations between SGLT2i use and cardiorenal events. In the cardiorenal outcome studies, patients with CKD who received canagliflozin or dapagliflozin had a lowered risk of a sustained decline in kidney function, end-stage kidney disease, or death from renal or cardiovascular (CV) causes than patients who received placebo. In outcome studies that enrolled patients with HFrEF, dapagliflozin, empagliflozin, and sotagliflozin lowered the risk of the composite endpoint of CV death and hospitalization for heart failure (HHF) versus placebo, an effect driven largely by a reduced risk of HHF. SGLT2i therapy was associated with risk reductions in the CV death/HHF composite and stand-alone HHF endpoints in patients with CKD. Conversely, patients with HFrEF attained renal benefit from SGLT2i use. The efficacy of SGLT2i was observed across a diverse range of patient subgroups. SGLT2i therapy has been found to substantially mitigate cardiorenal morbidity in patients with CKD or HFrEF, regardless of the presence of T2DM, and severity of CKD or HF.