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TYPE 2 DIABETES MELLITUS IN 2020

SGLT2 inhibitors in people with and without T2DM

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

  • 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.

  • 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.

  • Dapagliflozin and empagliflozin significantly reduce hospitalization for heart failure, and dapagliflozin significantly reduces cardiovascular death irrespective of T2DM status3,5.

  • Dapagliflozin and empagliflozin have significant beneficial effects on renal outcomes in people with and without T2DM5,6.

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Fig. 1: Potential mechanisms of SGLT2is in cardiorenal protection.

References

  1. 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).

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  2. 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).

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  5. Packer, M. et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N. Engl. J. Med. 383, 1413–1424 (2020).

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  6. Heerspink, H. J. L. et al. Dapagliflozin in patients with chronic kidney disease. N. Engl. J. Med. 383, 1436–1446 (2020).

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  7. 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).

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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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Correspondence to Kamlesh Khunti.

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Competing interests

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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