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Kidney and heart failure outcomes associated with SGLT2 inhibitor use

Nature Reviews Nephrology volume 18, pages 294–306 (2022)Cite this article

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Abstract

Chronic kidney disease (CKD) and heart failure affect many people worldwide. Despite the availability of pharmacological treatments, both diseases remain associated with considerable morbidity and mortality. After observations that sodium–glucose co-transporter 2 (SGLT2) inhibitors — originally developed as glucose-lowering agents — improved cardiovascular and renal outcomes in patients with type 2 diabetes, dedicated trials were initiated to evaluate the cardiovascular and kidney protective effects in patients with CKD or heart failure. The results of these clinical trials and subsequent detailed analyses have shown that the benefits of SGLT2 inhibitors are consistent across many patient subgroups, including those with and without type 2 diabetes, at different stages of CKD, and in patients with heart failure with preserved or reduced ejection fraction. In addition, post-hoc analyses revealed that SGLT2 inhibitors reduce the risk of anaemia and hyperkalaemia in patients with CKD. With respect to their safety, SGLT2 inhibitors are generally well tolerated. More specifically, no increased risk of hypoglycaemia has been observed in patients with CKD or heart failure without diabetes and they do not increase the risk of acute kidney injury. SGLT2 inhibitors therefore provide clinicians with an exciting new treatment option for patients with CKD and heart failure.

Key points

  • Individuals with chronic kidney disease (CKD) are at an increased risk of heart failure; conversely, kidney function decline is common in individuals with heart failure.

  • Sodium–glucose co-transporter 2 (SGLT2) inhibitors reduce the risk of kidney disease progression and hospitalization for heart failure, both in patients with CKD and in patients with heart failure.

  • The beneficial effects of SGLT2 inhibitors on kidney function and heart failure are consistent across stages of CKD and independent of the severity of heart failure.

  • SGLT2 inhibitors reduce the risk of anaemia and hyperkalaemia, which are common complications in patients with CKD or heart failure.

  • The characteristic decline in estimated glomerular filtration rate after initiation of SGLT2 inhibitors reflects their renal haemodynamic effects and is not associated with an increased risk of acute kidney injury or accelerated loss of kidney function.

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Fig. 1: Association between CKD and heart failure.
Fig. 2: Effect of SGLT2 inhibitors on kidney failure.
Fig. 3: Risk of acute kidney injury with SGLT2i use.
Fig. 4: Effect of SGLT2i on heart failure end points according to baseline kidney function.

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Authors and Affiliations

  1. Department of Clinical Pharmacy and Pharmacology, University of Groningen, Groningen, Netherlands

    Annemarie B. van der Aart-van der Beek & Hiddo J. L. Heerspink

  2. Department of Clinical Pharmacy, Martini Hospital, Groningen, Netherlands

    Annemarie B. van der Aart-van der Beek

  3. Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands

    Rudolf A. de Boer

  4. The George Institute for Global Health, Sydney, NSW, Australia

    Hiddo J. L. Heerspink

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  1. Annemarie B. van der Aart-van der Beek
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  2. Rudolf A. de Boer
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  3. Hiddo J. L. Heerspink
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The authors contributed equally to all aspects of the article.

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Correspondence to Hiddo J. L. Heerspink.

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Competing interests

R.A.d.B has received speaker fees from Abbott, AstraZeneca, Bayer, Novartis and Roche, is on the Executive Committee of the Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure (DELIVER) trial, sponsored by AstraZeneca, and is a study group member of the Dapagliflozin Effect on Exercise Capacity Using a 6-minute Walk Test in Patients With Heart Failure With Reduced Ejection Fraction and Preserved Ejection Fraction (DETERMINE Reduced & Preserved) trials, sponsored by AstraZeneca. H.J.L.H. has consulting relationships with AbbVie, AstraZeneca, Bayer, Boehringer Ingelheim, CSL Pharma, Chinook, Dimerix, Gilead, Janssen, Merck, Mitsubishi Tanabe, Mundi Pharma, NovoNordisk and Travere. A.B.v.d.A.-v.d.B. declares no competing interests.

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Nature Reviews Nephrology thanks Fan Fan Hou; Joshua Neumiller; and Sean Virani, who co-reviewed with Nima Moghaddam, for their contribution to the peer review of this work.

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van der Aart-van der Beek, A.B., de Boer, R.A. & Heerspink, H.J.L. Kidney and heart failure outcomes associated with SGLT2 inhibitor use. Nat Rev Nephrol 18, 294–306 (2022). https://doi.org/10.1038/s41581-022-00535-6

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