Effects of empagliflozin on risk for cardiovascular death and heart failure hospitalization across the spectrum of heart failure risk in the EMPA-REG OUTCOME® trial
Abstract
Aims: Empagliflozin reduced the risk of cardiovascular (CV) death and heart failure (HF) hospitalizations in patients with type 2 diabetes (T2D) and established CV disease (CVD) in the EMPA-REG OUTCOME® trial. We investigated whether the benefit of empagliflozin was observed across the spectrum of HF risk. Methods and results: Seven thousand and twenty patients with T2D (HbA1c 7-10% and eGFR > 30 mL/min/1.73 m2) were treated with empagliflozin 10 or 25 mg, or placebo once daily and followed for median 3.1 years. In patients without HF at baseline (89.9%), we derived the 5-year risk for incident HF using the 9-variable Health ABC HF Risk score [classified as low-to-average (<10%), high (10-20%), and very high (≥ 20%)]. Overall, 67.2% of the population had low-to-average, 24.2% high, and 5.1% very high 5-year HF risk. Across these groups, the effect on CV death and HF hospitalization with empagliflozin was consistent [hazard ratio 0.71 (95% confidence interval: 0.52, 0.96), 0.52 (0.36, 0.75), and 0.55 (0.30, 1.00), respectively]. Effects on CV death in the ostensibly highest HF risk group (HF at baseline and/or incident HF during the trial) in whom 37.9% of the overall CV deaths occurred, was also beneficial [0.67 (0.47, 0.97)], yet, similar benefits were seen in the lower risk patients. Conclusion: In patients with T2D and established CVD, a sizeable proportion without HF at baseline are at high or very high risk for HF outcomes, indicating the need for active case finding in this patient population. Empagliflozin consistently improved HF outcomes both in patients at low or high HF risk.
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SGLT2 inhibitors reduce the incidence of heart failure and improve heart failure-related outcomes, including hospitalization for heart failure and heart failure-related symptoms, in people with diabetes with preserved or reduced ejection fraction.
“SGLT2 inhibitors reduce the incidence of heart failure and improve heart failurerelated outcomes, including hospitalization for heart failure and heart failure-related symptoms, in people with diabetes with preserved or reduced ejection fraction (250,(255)(256)(257)(298)(299)(300)(301)(302)(303)(304)(305)(306).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [298]
The Introduction reports fewer heart-failure hospitalizations with empagliflozin in people with type 2 diabetes and cardiovascular disease, and the Discussion supports a benefit across levels of heart-failure risk. The paper does not report improvement in heart-failure symptoms or establish benefits separately for people with preserved versus reduced ejection fraction; the Discussion says measures of cardiac function were unavailable. Its direct findings concern empagliflozin, not SGLT2 inhibitors as a class. (LLM, conf=0.88)
Experimental — accuracy not yet measuredRates of heart failure hospitalization have been improved in recent trials of people with type 2 diabetes, most of whom also had ASCVD, using SGLT2 inhibitors.
“Rates of heart failure hospitalization have been improved in recent trials including people with type 2 diabetes, most of whom also had ASCVD, with sodium -glucose cotransporter 2 (SGLT2) inhibitors (8 -11).”
From 10. Cardiovascular Disease and Risk Management: <i>Standards of Care in Diabetes—2023</i> (2023) · cites this paper as [10]
In EMPAREG OUTCOME, the heart failure hospitalization benefit was consistent in patients with and without a history of heart failure.
“Although the majority of patients in the study did not have heart failure at baseline, this benefi t was consistent in patients with and without a history of heart failure (10).”
From 10. Cardiovascular Disease and Risk Management: <i>Standards of Care in Diabetes—2023</i> (2023) · cites this paper as [10]
Recent cardiovascular outcomes trials demonstrate that SGLT2 inhibitors may reduce heart failure morbidity and mortality and slow decline in renal function.
“Recent cardiovascular outcomes trials demonstrate that therapies that inhibit sodium glucose cotransporter (SGLT)2 may reduce heart failure morbidity and mortality and slow decline in renal function (7,8,23,42,43).”
From Evaluation of renal and cardiovascular protection mechanisms of SGLT2 inhibitors: model-based analysis of clinical data (2018) · cites this paper as [7]
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- Authors
- Fitchett, D., Butler, J., van de Borne, P., Zinman, B., Lachin, J. M., Wanner, C., Woerle, H. J., Hantel, S., George, J. T., Johansen, O. E., Inzucchi, S. E., & the EMPA-REG OUTCOME® trial investigators
- Affiliations
- St. Michael's Hospital (CA)
- Stony Brook University (US)
- Mount Sinai Hospital (CA)
- George Washington University (US)
- University of Würzburg (DE)
- Boehringer Ingelheim (Germany) (DE)
- Boehringer Ingelheim (Norway) (NO)
- Yale University (US)
- Corresponding author
- Fitchett, David
- ORCID
- Venue
- European Heart Journal
- Publisher
- Oxford University Press (OUP)
- Published
- 2017-08-28
- Volume
- 39
- Issue
- 5
- Pages
- 363-370
- ISSN
- 0195-668X (ISSN-L)
- 1522-9645
- OpenAlex
- W2760952310
- Cited by
- 242
- References
- 6
- Citations by year
- 2026: 2 · 2025: 14 · 2024: 14 · 2023: 11 · 2022: 15 · 2021: 30 · 2020: 50 · 2019: 56 · 2018: 42 · 2017: 5 · 2016: 2 · 2013: 1
- FWCI
- 33.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Heart Journal (publishedVersion)
- PubMed (publishedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- Lirias (KU Leuven) (submittedVersion)
- Funders
- Eli Lilly and Company
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Keywords
- empagliflozin, heart failure hospitalization, cardiovascular mortality, type 2 diabetes, established cardiovascular disease, heart failure risk stratification, incident heart failure, SGLT2 inhibitors, EMPA-REG OUTCOME trial, case finding
- MeSH terms
- Sodium-Glucose Transporter 2 Inhibitors, Aged, Benzhydryl Compounds, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Female, Glucosides, Heart Failure, Hospitalization, Humans, Male, Middle Aged, Risk Factors, Treatment Outcome
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