Use of sodium-glucose co-transporter-2 inhibitors in patients with and without type 2 diabetes: implications for incident and prevalent heart failure

Type 2 diabetes (T2D) is associated with an increased risk of heart failure (HF), with recent reports indicating that HF with preserved ejection fraction (HFpEF) may be more common than HF with reduced ejection fraction (HFrEF) in patients with T2D. T2D and HF result in worse outcomes than either disease alone. Sodium-glucose co-transporter-2 inhibitors (SGLT-2is) have significantly improved HF outcomes in patients with T2D and may represent a new therapeutic alternative for patients with T2D at risk for or with HF. Current guidelines recommend prevention of HF through risk factor management. Once developed, treatment of HFrEF should include neurohormonal and haemodynamic modulations; however, there are no specific treatments available for HFpEF. SGLT-2is are the first class of glucose-lowering therapy to prevent HF in clinical trials and real-world studies in patients with T2D (with or without established cardiovascular disease and with or without baseline HF). Mechanistic studies suggest that SGLT-2is have beneficial effects on both systolic and diastolic function and additional systemic effects that could benefit HF outcomes. In patients with HFrEF, SGLT-2i treatment as add-on to standard HF therapy has had beneficial effects on HF outcomes, irrespective of T2D status. These results and those of ongoing outcomes trials with SGLT-2is may help establish this drug class as a treatment for HF in patients with HFrEF and HFpEF, as well as HF in patients without T2D.