Kidney and heart failure outcomes associated with SGLT2 inhibitor use

Chronic kidney disease (CKD) and heart failure affect many people worldwide. Despite the availability of pharmacological treatments, both diseases remain associated with considerable morbidity and mortality. After observations that sodium–glucose co-transporter 2 (SGLT2) inhibitors — originally developed as glucose-lowering agents — improved cardiovascular and renal outcomes in patients with type 2 diabetes, dedicated trials were initiated to evaluate the cardiovascular and kidney protective effects in patients with CKD or heart failure. The results of these clinical trials and subsequent detailed analyses have shown that the benefits of SGLT2 inhibitors are consistent across many patient subgroups, including those with and without type 2 diabetes, at different stages of CKD, and in patients with heart failure with preserved or reduced ejection fraction. In addition, post-hoc analyses revealed that SGLT2 inhibitors reduce the risk of anaemia and hyperkalaemia in patients with CKD. With respect to their safety, SGLT2 inhibitors are generally well tolerated. More specifically, no increased risk of hypoglycaemia has been observed in patients with CKD or heart failure without diabetes and they do not increase the risk of acute kidney injury. SGLT2 inhibitors therefore provide clinicians with an exciting new treatment option for patients with CKD and heart failure. Clinical trials have demonstrated sodium–glucose co-transporter 2 (SGLT2) inhibitors to be safe and effective drugs that improve kidney outcomes in patients with and without diabetes. SGLT2 inhibitors also improve heart failure outcomes for patients with preserved or reduced ejection fraction. This Review summarizes findings from clinical trials of SGLT2 inhibitors, focusing on the effects of these agents in patients with chronic kidney disease and heart failure, and describes how potential mechanisms of action may translate into clinical benefit.