Graphical Abstract
Non-selective diuretic use in patients with heart failure succeeds in treating patients with true hypervolemia, but frequently leads to hypovolemia or excessive renal dysfunction and neurhormonal activation when administered to patients who were euvolemic at the time of administration. Administration of SGLT2 inhibitors (SGLT2i) may effectively improve the volume setpoint for the kidneys, allowing for volume excretion in the setting of hypervolemia, but allowing for counterregulatory mechanisms to preserve volume when euvolaemia is present.
After years of treatment decisions based upon expert consensus alone, patients with heart failure (HF) and preserved ejection fraction (HFpEF) finally have a robust, evidence-based treatment in the sodium–glucose co-transporter 2 (SGLT2) inhibitors.[1] The SGLT2 inhibitors dapagliflozin and empagliflozin have been shown to reduce the composite of HF hospitalization and cardiovascular death, improve patient-reported health status, enhance functional capacity, and delay the age-related reduction in kidney function in patients with HFpEF and HF with mildly reduced EF (HFmrEF).[2–4]However, the mechanisms responsible for these salutary effects remain unclear. Although data vary across studies, SGLT2 inhibitors appear to reduce plasma volume and body weight, promote natriuresis and diuresis, improve intraglomerular haemodynamics, stimulate erythropoiesis, and enhance nutrient deprivation signalling pathways, and may also improve myocardial structure and function.
