Heart failure risk stratification and efficacy of sodium-glucose cotransporter-2 inhibitors in patients with type 2 diabetes mellitus
Open accessAbstract
Background: Patients with type 2 diabetes mellitus (T2DM) are at increased risk of developing heart failure. Sodium-glucose cotransporter-2 inhibitors reduce the risk of hospitalization for heart failure (HHF) in patients with T2DM. We aimed to develop and validate a practical clinical risk score for HHF in patients with T2DM and assess whether this score can identify high-risk patients with T2DM who have the greatest reduction in risk for HHF with a sodium-glucose cotransporter-2 inhibitor. Methods: We developed a clinical risk score for HHF in 8212 patients with T2DM in the placebo arm of SAVOR-TIMI 53 (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients With Diabetes Mellitus–Thrombolysis in Myocardial Infarction 53). Candidate variables were assessed using multivariable Cox regression, and independent clinical risk indicators achieving statistical significance of P <0.001 were included in the risk score. We externally validated the score in 8578 patients with T2DM in the placebo arm of DECLARE-TIMI 58 (Dapagliflozin Effect on Cardiovascular Events–Thrombolysis in Myocardial Infarction 58). The relative and absolute risk reductions in HHF with the sodium-glucose cotransporter-2 inhibitor dapagliflozin were assessed by baseline HHF risk. Results: Five clinical variables were independent risk predictors of HHF: prior heart failure, history of atrial fibrillation, coronary artery disease, estimated glomerular filtration rate, and urine albumin-to-creatinine ratio. A simple integer-based score (0–7 points) using these predictors identified a >20-fold gradient of HHF risk ( P for trend <0.001) in both the derivation and validation cohorts, with C indices of 0.81 and 0.78, respectively. Although relative risk reductions with dapagliflozin were similar for patients across the risk scores (25%–34%), absolute risk reductions were greater in those at higher baseline risk (1-sided P for trend=0.04), with high-risk (2 points) and very-high-risk (≥3 points) patients having 1.5% and 2.7% absolute reductions in Kaplan-Meier estimates of HHF risk at 4 years, respectively. Conclusions: Risk stratification using a novel clinical risk score for HHF in patients with T2DM identifies patients at higher risk for HHF who derive greater absolute benefit from sodium-glucose cotransporter-2 inhibition. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifiers: NCT01107886 and NCT01730534.
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While greater reductions in HF hospitalization risk are observed with SGLT2 inhibitor therapy in individuals with higher baseline HF risk, some benefit is observed across the full range of HF risk.
“Similarly, while greater reductions in HF hospitalization risk are observed with SGLT2 inhibitor therapy in individuals with higher baseline HF risk, some benefit is observed across the full range of HF risk (135).”
From 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025 (2025) · cites this paper as [135]
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- Authors
- Berg, D. D., Wiviott, S. D., Scirica, B. M., Gurmu, Y., Mosenzon, O., Murphy, S. A., Bhatt, D. L., Leiter, L. A., McGuire, D. K., Wilding, J. P. H., Johanson, P., Johansson, P. A., Langkilde, A. M., Raz, I., Braunwald, E., & Sabatine, M. S.
- Affiliations
- Brigham and Women's Hospital (US)
- Hadassah Medical Center (IL)
- St. Michael's Hospital (CA)
- The University of Texas Southwestern Medical Center (US)
- University of Liverpool (GB)
- AstraZeneca (Sweden) (SE)
- TIMI Study Group, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA (D.D.B., S.D.W., B.M.S., Y.G., S.A.M., D.L.B., E.B., M.S.S.).
- ORCID
- Venue
- Circulation
- Published
- 2019-11-05
- Volume
- 140
- Issue
- 19
- Pages
- 1569-1577
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- PMC
- PMC6829059
- OpenAlex
- W2970346174
- Cited by
- 154
- References
- 8
- Citations by year
- 2026: 20 · 2025: 16 · 2024: 16 · 2023: 18 · 2022: 24 · 2021: 32 · 2020: 25 · 2019: 2
- FWCI
- 16.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (T32HL007604)
- 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
- heart failure risk stratification, SGLT2 inhibitors, dapagliflozin, type 2 diabetes, heart failure hospitalization, clinical risk score, risk prediction model, atrial fibrillation, coronary artery disease, estimated glomerular filtration rate, albuminuria, SAVOR-TIMI 53, DECLARE-TIMI 58
- MeSH terms
- Clinical Decision-Making, Sodium-Glucose Transporter 2 Inhibitors, Adamantane, Aged, Benzhydryl Compounds, Decision Support Techniques, Diabetes Mellitus, Type 2, Dipeptides, Female, Glucosides, Health Status, Heart Failure, Humans, Male, Middle Aged, Predictive Value of Tests, Risk Factors, Time Factors, Reproducibility of Results, Randomized Controlled Trials as Topic, Treatment Outcome, Risk Assessment, Patient Selection, Dipeptidyl-Peptidase IV Inhibitors, Diabetic Cardiomyopathies
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