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CARDIOVASCULAR DISEASE

SGLT-2 inhibitors in heart failure: a new therapeutic avenue

Nature Medicine volume 25, pages 1653–1654 (2019)Cite this article

Subjects

Dapagliflozin, a sodium-glucose co-transporter-2 inhibitor, reduced the risk of cardiovascular death or heart failure events in 4,744 patients with chronic heart failure with reduced ejection fraction.

The inhibition of sodium-glucose co-transporter-2 (SGLT2), the principal protein responsible for the reclamation of filtered glucose in the proximal renal tubule, has become the target of intense recent pharmacological interest. These therapies were initially designed for glycemic regulation in diabetes mellitus (DM), but their potential scope of application is now recognized to be considerably broader. Phlorizin is a naturally occurring, non-selective SGLT inhibitor that was first extracted in 1835 from the bark of apple trees by French scientists1, and it took over 150 years for the development of synthetic, more specific SGLT2 inhibitor analogs. There are now four SGLT2 inhibitors commercially available in the United States. In their initial safety evaluation in patients with type 2 DM as mandated by a US Food and Drug Administration (FDA) regulatory guidance2, not only were they all safe with respect to cardiovascular effects, but they also led to unexpected and profound benefits: preventing hospitalization for heart failure (HF) by 25–35%3 and reducing clinically relevant kidney outcomes4.

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Fig. 1: A timeline of the discovery and evaluation of SGLT2 inhibitors.

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Authors and Affiliations

  1. Brigham and Women’s Hospital Heart & Vascular Center and Harvard Medical School, Boston, MA, USA

    Muthiah Vaduganathan

  2. Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA

    Javed Butler

Authors
  1. Muthiah Vaduganathan
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  2. Javed Butler
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Corresponding author

Correspondence to Javed Butler.

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Competing interests

M.V. is supported by the KL2/Catalyst Medical Research Investigator Training award from Harvard Catalyst (NIH/NCATS Award UL 1TR002541), serves on advisory boards for Amgen, AstraZeneca, Baxter Healthcare, Bayer AG, Boehringer Ingelheim and Relypsa, and participates on clinical endpoint committees for studies sponsored by Novartis and the NIH. J.B. has served as a consultant to Abbott, Amgen, Array, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, CVRx, G3 Pharma, Gilead, Impulse Dynamics, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, NovoNordisk, Relypsa, Roche, Sanofi, V-Wave Limited and Vifor.

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Vaduganathan, M., Butler, J. SGLT-2 inhibitors in heart failure: a new therapeutic avenue. Nat Med 25, 1653–1654 (2019). https://doi.org/10.1038/s41591-019-0647-4

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