Could SGLT2 Inhibitors Improve Exercise Intolerance in Chronic Heart Failure?

Suzanne N. Voorrips*, Huitzilihuitl Saucedo-Orozco, Pablo I. Sánchez-Aguilera, Rudolf A. De Boer, Peter Van der Meer, B. Daan Westenbrink*

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

9 Citations (Scopus)


Despite the constant improvement of therapeutical options, heart failure (HF) remains associated with high mortality and morbidity. While new developments in guideline-recommended therapies can prolong survival and postpone HF hospitalizations, impaired exercise capacity remains one of the most debilitating symptoms of HF. Exercise intolerance in HF is multifactorial in origin, as the underlying cardiovascular pathology and reactive changes in skeletal muscle composition and metabolism both contribute. Recently, sodium-related glucose transporter 2 (SGLT2) inhibitors were found to improve cardiovascular outcomes significantly. Whilst much effort has been devoted to untangling the mechanisms responsible for these cardiovascular benefits of SGLT2 inhibitors, little is known about the effect of SGLT2 inhibitors on exercise performance in HF. This review provides an overview of the pathophysiological mechanisms that are responsible for exercise intolerance in HF, elaborates on the potential SGLT2-inhibitor-mediated effects on these phenomena, and provides an up-to-date overview of existing studies on the effect of SGLT2 inhibitors on clinical outcome parameters that are relevant to the assessment of exercise capacity. Finally, current gaps in the evidence and potential future perspectives on the effects of SGLT2 inhibitors on exercise intolerance in chronic HF are discussed.

Original languageEnglish
Article number8631
JournalInternational Journal of Molecular Sciences
Issue number15
Publication statusPublished - Aug 2022
Externally publishedYes

Bibliographical note

Funding Information:
The UMCG, which employs all of the authors, received research grants and/or fees from AstraZeneca, Abbott, Boehringer Ingelheim, Cardior Pharmaceuticals Gmbh, Ionis Pharmaceuticals, Inc., Novo Nordisk, and Roche. RAdB has received grants from the Netherlands Heart Foundation (DOUBLE DOSE 2020) and the European Research Council (ERC CoG 818715, SECRETE-HF) and received speaker fees from Abbott, AstraZeneca, Bayer, Novartis, and Roche. PvdM has received consultancy fees and/or grants from Novartis, Novo Nordisk, Vifor Pharma, Astra Zeneca, Pfizer, Pharmacosmos, Pharma Nord, and Ionis. BDW has received consulting fees from Boehringer Ingelheim, Novartis, and Astra Zeneca and has received research grants from the Netherlands Organisation for Scientific Research (NOW VENI, grant 016.176.147), Siemens, Bristol-Myers Squibb and the Netherlands Heart Foundation (DOUBLE DOSE 2020 and the Senior Clinical Scientist Grant 2019T064). All other authors have nothing to declare.

Publisher Copyright:
© 2022 by the authors.


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