Clinical Considerations for Use of SGLT2 Inhibitor Therapy in Patients with Heart Failure and Reduced Ejection Fraction: A Review

Heart failure (HF) continues to increase in prevalence, representing a significant burden to healthcare systems in the USA. Despite several established HF therapies, particularly for HF with reduced ejection fraction (HFrEF), rates of HF hospitalizations and cardiovascular (CV) mortality remain very high. Type 2 diabetes (T2D) is an important risk factor for HF, with the two conditions often occurring concurrently. Several CV outcomes trials have shown that the sodium-glucose cotransporter 2 inhibitor (SGLT2i) class of antihyperglycemic drugs reduces the risk of HF-related outcomes in patients with T2D and either established CV disease or multiple CV risk factors. Subsequently, there have been large clinical studies that have investigated the effects of SGLT2is in patients with HFrEF, with or without T2D, which have shown that both dapagliflozin and empagliflozin have significant reductions in hospitalization for HF and CV mortality. These data led to US Food and Drug Administration approval of dapagliflozin and empagliflozin as a novel treatment pathway for patients with HFrEF; empagliflozin has subsequently been approved for the treatment of HF regardless of ejection fraction. A clinical practice algorithm can assist cardiologists in identifying patients who may be eligible for SGLT2i treatment as well as the appropriate timeframe for initiating therapy and the parameters for patient monitoring. Given the evidence that SGLT2is are beneficial in the management of HF, specifically HFrEF, irrespective of underlying T2D, evidence-based recommendations and greater clinician familiarity can facilitate the integration of SGLT2is into general HF therapeutic management.