Clinical pharmacology of SGLT-2 inhibitors in heart failure

ABSTRACT

Introduction

Sodium-glucose cotransporter 2 (SGLT2) inhibitors constitute a class of oral antiglycemic agents that have emerged as a new therapeutic strategy for heart failure (HF) with reduced ejection fraction (HFrEF) and, potentially, for HF with preserved ejection fraction (HFpEF).

Areas covered

Ongoing efforts to clarify the exact mechanisms of action of SGLT2 inhibitors (SGLT2i) reveal that glycosuria and osmotic diuresis, resulting from the blockade of renal receptors, is not the sole pathophysiological mechanism. Nevertheless, the underlying mechanisms, accounting for their cardiovascular beneficial effects which have been clearly demonstrated in clinical trials, remain unclear. The aim of this review is to summarize the primary outcomes of large-scale studies regarding the use of SGLT2i in HF and provide an overview of the potential pathways involved in the SGLT2i-mediated cardioprotection.

Expert opinion

SGLT2i exhibit favorable pleiotropic effects, which extend beyond their primary indication as pharmaceutical agents intended for glycemic control. Given their unique pathophysiological profile, these agents have revolutionized the management of HF, while in the near future, it is possible that evolving research in the field may unfold further perspectives on their potential use in the treatment of other chronic conditions.

KEYWORDS:

• Dapagliflozin
• empagliflozin
• heart failure
• SGLT2 inhibitors
• sotagliflozin

Article highlights

• SGLT2 inhibitors are a class of oral antiglycemic agents that have emerged as a new therapeutic strategy for heart failure.

• SGLT2 inhibitors demonstrate favorable pleiotropic effects whicheffects that extend beyond their initial indication as pharmaceutical agents intended for glycemic control.

• Large scaleLarge-scale clinical trials demonstrated a decreased risk of heart failure hospitalizations and cardiovascular mortality following the use of SGLT2 inhibitors, irrespective of diabetes mellitus status.

• Apart from their glycosuric and natriuretic effects, SGLT2 inhibitors might also have direct effects on cardiac, endothelialendothelial, and vascular smooth muscle cells and exert anti-fibrotic and anti-inflammatory actions.

• SGLT2 inhibitors have revolutionized the management of HF and they might potentially represent a promising agent for the treatment of other chronic conditions in the future.

Declaration of interest

JT Parissis has received honoraria for lectures and advisory boards by AstraZeneca and Boehringer Ingelheim. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.