Sodium-glucose cotransporter 2 inhibitors as a treatment for heart failure

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been shown to prevent the 2 development of heart failure (HF) in patients with type 2 diabetes with established (or at high 3 risk of) cardiovascular disease. The finding that this benefit was independent of any glucose 4 lowering effect prompted the development of a series of clinical trials examining the potential 5 role of SGLT2i as a treatment for HF. In two large, randomised, placebo-controlled trials in 6 patients with chronic HF and reduced ejection fraction (HFrEF), the SGLT2i dapagliflozin and 7 empagliflozin reduced the risk of cardiovascular death and worsening HF, and improved 8 symptoms and quality of life, when added to guideline recommended pharmacological and 9 device therapy. The benefits of SGLT2i in HFrEF were consistent regardless of the presence or 10 absence of type 2 diabetes. These results have established SGLT2i as one of the cornerstones of 11 HFrEF pharmacotherapy along with an angiotensin receptor-neprilysin inhibitor, beta-blocker 12 and mineralocorticoid receptor antagonist. We summarise the evidence for the use of SGLT2i as 13 a treatment for HFrEF, provide practical guidance for their implementation and give insight into 14 ongoing trials with this class of drug across the HF landscape.