SGLT2 inhibitors: an evidence-based update on cardiovascular implications

ABSTRACT

Introduction

Sodium Glucose co-Transporter 2 (SGLT2) inhibitors (also known as ‘gliflozins’) represent a cornerstone to treat diabetes mellitus. Moreover, recent randomized clinical trials have demonstrated important cardioprotective effects of gliflozins, independent of the presence of diabetes. Herein, we summarize the recent therapeutic progress in the cardiovascular field obtained with SGLT2 inhibitors.

Area covered

We critically examine the rationale and results of recent clinical studies examining the effects of SGLT2 inhibitors on cardiovascular outcomes, along with a brief overview of the main ongoing trials that have been designed in order to answer the many pending questions in the field of gliflozins and cardiovascular disease.

Expert opinion

The favorable results of several clinical trials have broadened the therapeutic scenario for SGLT2 inhibitors, opening, at the same time, new challenges. Additionally, recent preclinical findings have evidenced off-target effects of SGLT2 inhibitors.

KEYWORDS:

• Canagliflozin
• dapagliflozin
• empagliflozin
• ertugliflozin
• heart failure
• HFpEF
• SGLT2i

Article highlights

• Sodium Glucose co-Transporter 2 (SGLT2) inhibitors emerged as a main therapeutic option for patients with type 2 diabetes mellitus.

• Recent randomized clinical trials unveiled unprecedented cardioprotective actions of SGLT2 inhibitors.

• The favorable effects of SGLT2 inhibitors on cardiovascular outcome are not dependent on the presence of diabetes.

• We present an overview of the recent therapeutic progress in the cardiovascular field obtained with SGLT2 inhibitors, including ongoing clinical trials.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

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

Additional information

Funding

The Santulli’s Lab is currently supported in part by the National Institutes of Health (NIH): National Heart, Lung, and Blood Institute (NHLBI: R01-HL164772, R01-HL159062, R01-HL146691, T32-HL144456), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK: R01-DK123259, R01-DK033823), National Center for Advancing Translational Sciences (NCATS: UL1-TR002556-06, UM1-TR004400) to G.S., by the Diabetes Action Research and Education Foundation (to G.S.), by the Waxman Research Foundation (to G.S.), and by the Monique Weill-Caulier and Irma T. Hirschl Trusts (to G.S.). S.W. is supported in part by a Glorney Rainsbek Fellowship (New York Academy of Medicine, NYAM). S.S.J. is supported in part by a postdoctoral fellowship of the American Heart Association (AHA-21POST836407). U.K. is supported in part by a postdoctoral fellowship of the American Heart Association (AHA-23POST1026190). F.V. is supported in part by a postdoctoral fellowship of the American Heart Association (AHA-22POST915561).