Heart failure and chronic kidney disease are frequent causes of morbidity and mortality in people with type 2 diabetes mellitus. Cardiovascular outcome trials have confirmed benefits of sodium–glucose co-transporter 2 inhibitors on cardiovascular events, cardiovascular deaths, hospitalization for heart failure and renal outcomes. These benefits now extend to people with and without type 2 diabetes mellitus.
Key advances
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Sodium–glucose co-transporter 2 inhibitors significantly reduce the risk of major cardiovascular events, cardiovascular death or hospitalization for heart failure and progression of chronic kidney disease in people with type 2 diabetes mellitus (T2DM) with or without atherosclerotic cardiovascular disease2.
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Dapagliflozin and empagliflozin have shown significant beneficial effects on the composite outcome of worsening of heart failure or cardiovascular death in patients with New York Heart Association Class 2, 3 or 4 heart failure with or without T2DM3,5.
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Dapagliflozin and empagliflozin significantly reduce hospitalization for heart failure, and dapagliflozin significantly reduces cardiovascular death irrespective of T2DM status3,5.
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Dapagliflozin and empagliflozin have significant beneficial effects on renal outcomes in people with and without T2DM5,6.
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References
Birkeland, K. I. et al. Heart failure and chronic kidney disease manifestation and mortality risk associations in type 2 diabetes: A large multinational cohort study. Diabetes Obes. Metab. 22, 1607–1618 (2020).
Qiu, M. et al. SGLT2 inhibitors for prevention of cardiorenal events in people with type 2 diabetes without cardiorenal disease: A meta-analysis of large randomized trials and cohort studies. Pharmacol. Res. 161, 105175 (2020).
McMurray, J. J. V. et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N. Engl. J. Med. 381, 1995–2008 (2019).
Cannon, C. P. et al. Cardiovascular outcomes with ertugliflozin in type 2 diabetes. N. Engl. J. Med. 383, 1425–1435 (2020).
Packer, M. et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N. Engl. J. Med. 383, 1413–1424 (2020).
Heerspink, H. J. L. et al. Dapagliflozin in patients with chronic kidney disease. N. Engl. J. Med. 383, 1436–1446 (2020).
Zannad, F. et al. SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR-Reduced and DAPA-HF trials. Lancet 396, 819–829 (2020).
Acknowledgements
K.K. is supported by the National Institute for Health Research (NIHR) Applied Research Collaboration East Midlands (ARC EM) and the NIHR Leicester Biomedical Research Centre (BRC).
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K.K. has acted as a consultant, speaker or received grants for investigator-initiated studies for AstraZeneca, Bayer, Berlin-Chemie AG/Menarini Group, Boehringer Ingelheim, Janssen, Lilly, Merck Sharp & Dohme, Napp, Novartis, Novo Nordisk and Sanofi-Aventis.
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Khunti, K. SGLT2 inhibitors in people with and without T2DM. Nat Rev Endocrinol 17, 75–76 (2021). https://doi.org/10.1038/s41574-020-00453-2
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DOI: https://doi.org/10.1038/s41574-020-00453-2
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