Skip to main content

Sodium‑glucose co-transporter‑2 inhibitors in the treatment of diabetes with heart failure

Abstract

2022 AHA/ACC/HFSA guideline for the management of heart failure, which is valuable for clinical decision-making, was recently released. This guideline recommended patients with heart failure with type 2 diabetes sodium‑glucose co-transporter‑2 inhibitors for the management of hyperglycemia and to reduce heart failure-related morbidity and mortality (Class 1, Level A). It is important to note that the source of evidence based on this recommendation is from EMPEROR-Reduced, DAPA-HF, and DECLARE-TIMI 58 and does not include newly published PRESERVED-HF, CHIEF-HF, and EMPEROR-Preserved. Here we reviewed these important trials in order to provide more clinical references for patients with diabetes and heart failure, especially heart failure with preserved ejection fraction.

Recently, the 2022 AHA/ACC/HFSA guideline for the management of heart failure was released [1]. The 2022 heart failure guideline provides recommendations based on contemporary evidence for the treatment of these patients. The recommendations present an evidence-based approach to managing patients with heart failure, with the intent to improve the quality of care and align with patients’ interests. The publication of some landmark clinical trials may rewrite the guideline, but the guideline is not referenced. The 2022 guideline stated in patients with heart failure and type 2 diabetes, the use of sodium‑glucose co-transporter‑2 inhibitors is recommended for the management of hyperglycemia and to reduce heart failure-related morbidity and mortality (Class 1, Level A) [1] based on EMPEROR-Reduced [2], DAPA-HF [3], and DECLARE-TIMI 58 [4]. It is worth noting that empagliflozin/dapagliflozin reduced cardiovascular death and hospitalization for heart failure in patients with heart failure and diabetes, but the ejection fraction was ≤ 40% in EMPEROR-Reduced [2] and DAPA-HF [3], < 45% in DECLARE-TIMI 58 [4], respectively. In other words, empagliflozin/dapagliflozin only reduces cardiovascular outcomes in diabetes with heart failure with reduced ejection fraction and partial mildly reduced ejection fraction. Notably, PRESERVED-HF and CHIEF-HF indicated that dapagliflozin/canagliflozin improved surrogate endpoints (such as Kansas City Cardiomyopathy Questionnaire total symptom score) in patients with diabetes and heart failure (ejection fraction was ≥ 45% in PRESERVED-HF and was not limited in CHIEF-HF) [5, 6]. Moreover, EMPEROR-Preserved was released that empagliflozin reduced the combined risk of cardiovascular death or hospitalization for heart failure in patients with heart failure with preserved ejection fraction (more than 40%), regardless of the presence or absence of diabetes [7]. Ongoing DELIVER will provide new evidence for dapagliflozin in patients with heart failure with preserved ejection fraction (more than 40%) with or without diabetes [8].

Collectively, our current evidence mainly focuses on empagliflozin/dapagliflozin in the treatment of diabetes with heart failure with reduced ejection fraction [9] and empagliflozin in the treatment of diabetes with heart failure with preserved ejection fraction. The role of other types of sodium‑glucose co-transporter‑2 inhibitors in diabetes with heart failure, especially in diabetes with heart failure with preserved ejection fraction, still needs high-quality evidence.

Availability of data and materials

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

References

  1. Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: a report of the American college of cardiology/American heart association joint committee on clinical practice guidelines. J Am Coll Cardiol. 2022. https://doi.org/10.1016/j.jacc.2021.12.012.

    Article  PubMed  Google Scholar 

  2. Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, Januzzi J, Verma S, Tsutsui H, Brueckmann M, et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med. 2020;383(15):1413–24.

    CAS  Article  Google Scholar 

  3. McMurray JJV, Solomon SD, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Anand IS, Bělohlávek J, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;381(21):1995–2008.

    CAS  Article  Google Scholar 

  4. Kato ET, Silverman MG, Mosenzon O, Zelniker TA, Cahn A, Furtado RHM, Kuder J, Murphy SA, Bhatt DL, Leiter LA, et al. Effect of dapagliflozin on heart failure and mortality in type 2 diabetes mellitus. Circulation. 2019;139(22):2528–36.

    CAS  Article  Google Scholar 

  5. Nassif ME, Windsor SL, Borlaug BA, Kitzman DW, Shah SJ, Tang F, Khariton Y, Malik AO, Khumri T, Umpierrez G, et al. The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial. Nat Med. 2021;27(11):1954–60.

    Article  Google Scholar 

  6. Spertus JA, Birmingham MC, Nassif M, Damaraju CV, Abbate A, Butler J, Lanfear DE, Lingvay I, Kosiborod MN, Januzzi JL. The SGLT2 inhibitor canagliflozin in heart failure: the CHIEF-HF remote, patient-centered randomized trial. Nat Med. 2022. https://doi.org/10.1038/s41591-022-01703-8.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Anker SD, Butler J, Filippatos G, Ferreira JP, Bocchi E, Böhm M, Brunner-La Rocca H-P, Choi D-J, Chopra V, Chuquiure-Valenzuela E, et al. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med. 2021;385(16):1451–61.

    CAS  Article  Google Scholar 

  8. Solomon SD, Vaduganathan M, Claggett BL, de Boer RA, DeMets D, Hernandez AF, Inzucchi SE, Kosiborod MN, Lam CSP, Martinez F, et al. Baseline characteristics of patients with hf with mildly reduced and preserved ejection fraction: DELIVER trial. JACC Heart Fail. 2022;10(3):184–97.

    Article  Google Scholar 

  9. Liang B, Zhao Y-X, Zhang X-X, Liao H-L, Gu N. Reappraisal on pharmacological and mechanical treatments of heart failure. Cardiovasc Diabetol. 2020;19(1):55.

    Article  Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

Not applicable.

Author information

Authors and Affiliations

Authors

Contributions

BL and NG conceived, designed, and planned the study. BL and NG acquired and analyzed the data. BL drafted the manuscript and NG contributed to the critical revision of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Ning Gu.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Liang, B., Gu, N. Sodium‑glucose co-transporter‑2 inhibitors in the treatment of diabetes with heart failure. Cardiovasc Diabetol 21, 84 (2022). https://doi.org/10.1186/s12933-022-01526-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12933-022-01526-4

Keyword

  • Sodium‑glucose co-transporter‑2 inhibitors
  • Diabetes
  • Heart failure