Cardiorenal Hemodynamic Effects of SGLT2 Inhibitors Across Heart Failure Phenotypes: A Structured Narrative Review

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have become the mainstay treatment for heart failure with reduced ejection fraction (HFrEF) and have found wider applications in other forms of heart failure as well. Despite their known beneficial impact, how much of this benefit is attributed to the actual cardiorenal hemodynamic effect versus association with surrogate parameters or clinical endpoints remains unknown.

This narrative review evaluates available evidence from 2012-2026, collected from PubMed, Scopus, and Web of Science databases. Eligible literature includes randomized controlled trials, prospective studies, mechanistic studies of kidney physiology, biomarker studies, and relevant meta-analyses on the use of SGLT2i in heart failure and cardiorenal diseases. Available evidence is classified by study type into hemodynamic studies, renal physiology studies, studies on surrogate markers, and clinical studies.

The strongest evidence concerning the role of SGLT2i in heart failure comes from their use in patients with HFrEF. Specifically, SGLT2 inhibitors dapagliflozin and empagliflozin have been shown to reduce heart failure exacerbation and cardiovascular deaths. In cases of HFmrEF and HFpEF, the beneficial effects of SGLT2 inhibitors can be attributed to a reduced risk of heart failure-related complications such as hospitalization. From the standpoint of the underlying mechanism of action, SGLT2i are associated with osmotic diuresis and natriuresis, restored tubuloglomerular feedback, reduced blood pressure, and maintenance of renal function. However, their impact on myocardial bioenergetics, inflammatory state, endothelial health, and myocardial remodeling is supported mainly by mechanistic, translational, and indirect clinical evidence rather than direct hemodynamic trials.

Based on current literature, it can be argued that the SGLT2 inhibitors have been consistently providing clinical and renal benefits for HF phenotypes; however, the observed effects cannot be used to claim a single mechanism based on the hemodynamic pathway. Improvement of biomarkers and benefits on clinical outcomes confirm the biological plausibility; however, data from direct invasively assessed hemodynamics are lacking.

Sodium-glucose cotransporter 2 inhibitors have shown clear evidence-based cardiorenal benefits in HFrEF and reduction of HF hospitalizations in HFmrEF and HFpEF.