SGLT2 inhibitors and new frontiers in heart failure treatment regardless of ejection fraction and setting.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been shown to reduce cardiovascular (CV) mortality and heart failure (HF) hospitalizations, independently from left ventricular ejection fraction (EF). Their efficacy has been assessed both in patients with reduced and preserved EF, with notable benefits in renal outcomes as well. The initiation of SGLT2i in the early phase of hospitalization for acute HF has proven to be safe and beneficial. The EMPULSE and DICTATE-AHF trials support early empagliflozin and dapagliflozin use, respectively, reducing worsening HF events, improving quality of life, and enhancing diuretic efficiency. Notably, these benefits emerge shortly after the initiation of therapy, underscoring the importance of early integration into guideline-directed medical therapy (GDMT). Despite concerns regarding deterioration of renal function, SGLT2i appear to be safe even in patients with low estimated glomerular filtration rates (eGFR). Data suggest that SGLT2i benefits persist without increased safety risks, reassuring clinicians of their efficacy in patients experiencing renal decline. Concerns about volume depletion induced by SGLT2i have also been addressed, with documented enhanced diuresis without adverse renal impacts. Moreover, SGLT2i have been associated with a lower risk of hyperkalaemia events, thus allowing for better optimization of GDMT, including the use of mineralocorticoid receptor antagonists. Overall, these findings highlight the broad CV, renal, and metabolic benefits of SGLT2i, advocating for their early and widespread use in HF management, regardless of EF or eGFR.