Effects of Canagliflozin on Amino-Terminal Pro–B-Type Natriuretic Peptide
Open accessAbstract
BACKGROUND: Canagliflozin reduces cardiovascular events including hospitalization for heart failure (HHF) in patients with type 2 diabetes and cardiovascular risk. Elevated amino-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations are associated with HF diagnosis and predict cardiovascular risk. OBJECTIVES: The purpose of this study was to measure NT-proBNP in CANVAS (Canagliflozin Cardiovascular Assessment Study) participants. METHODS: Associations between baseline NT-proBNP and cardiovascular, renal, and mortality outcomes and intervention-associated changes were determined. RESULTS: Of the 4,330 participants in the CANVAS trial, NT-proBNP was measured in 3,587, 2,918, and 995 participants at baseline, 1 year, and 6 years, respectively. The median baseline NT-proBNP concentration was 91 pg/ml, and 39.3% had NT-proBNP ≥125 pg/ml. NT-proBNP was higher in those with investigator-reported HF (13% of participants at baseline) versus those without (187 pg/ml vs. 81 pg/ml), with substantial overlap between groups. By 1 year, NT-proBNP increased with placebo, whereas canagliflozin reduced NT-proBNP by 11% (geometric mean ratio for canagliflozin vs. placebo = 0.89 [95% confidence interval (CI): 0.84 to 0.94]; p < 0.001). Lower NT-proBNP with canagliflozin was also observed at 6 years (p = 0.004). In adjusted models, baseline NT-proBNP ≥125 pg/ml was prognostic for incident HHF (hazard ratio [HR]: 5.40; 95% CI: 2.67 to 10.9), HHF/cardiovascular death (HR: 3.52; 95% CI: 2.38 to 5.20), and all-cause death (HR: 2.53; 95% CI: 1.78 to 3.61). Mediation analyses suggested that 10.4% of the effects of canagliflozin on HHF were reflected in NT-proBNP lowering. CONCLUSIONS: A substantial percentage of patients in the CANVAS trial had elevated NT-proBNP values. Canagliflozin reduced NT-proBNP concentrations versus placebo; however, reduction in NT-proBNP explained only a small proportion of the benefit of canagliflozin on HF events. (CANVAS [CANagliflozin cardioVascular Assessment Study]; NCT01032629).
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In people with type 2 diabetes, measurement of natriuretic peptides, including BNP or NT-proBNP, identifies people at risk for heart failure development, progression of symptoms, and heart failure-related mortality.
“In people with type 2 diabetes, measurement of natriuretic peptides, including B-type natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP), identifies people at risk for heart failure development, progression of symptoms, and heart failure-related mortality (223-225).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [223]
The Discussion reports that elevated NT-proBNP is associated with incident heart failure in people with type 2 diabetes, and the outcomes analysis finds baseline NT-proBNP prognostic for heart-failure hospitalization and the combined outcome of hospitalization or cardiovascular death. The paper does not establish the same findings for BNP measured separately, symptom progression, or heart-failure-related mortality specifically. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIn people with type 2 diabetes, measurement of natriuretic peptides, including BNP or NT-proBNP, identifies people at risk for heart failure development, progression of symptoms, and heart failure-related mortality.
“In people with type 2 diabetes, measurement of natriuretic peptides, including B-type natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP), identifies people at risk for heart failure development, progression of symptoms, and heart failure–related mortality (212–214).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [212]
The Discussion reports that elevated NT-proBNP is associated with incident heart failure in people with type 2 diabetes, and the results find baseline NT-proBNP prognostic for heart-failure hospitalization. The paper does not establish symptom progression or heart-failure-specific mortality as outcomes predicted by these measurements; it reports cardiovascular-death composites and all-cause death instead. The evidence presented concerns NT-proBNP, not a separate BNP measurement. (LLM, conf=0.87)
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Limitations of Natriuretic Peptide Levels in Establishing SGLT-2 Inhibitors for Heart Failure Care
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Self-citation
- Authors
- Januzzi, J. L., Xu, J., Li, J., Shaw, W., Oh, R., Pfeifer, M., Butler, J., Sattar, N., Mahaffey, K. W., Neal, B., & Hansen, M. K.
- Affiliations
- Massachusetts General Hospital (US)
- Janssen Research & Development (United States) (US)
- Army Medical University (CN)
- Janssen Scientific Affairs (United States) (US)
- University of Mississippi (US)
- University of Glasgow (GB)
- Stanford Medicine (US)
- The University of Sydney (AU)
- Corresponding author
- Januzzi, James L.
- ORCID
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2020-11
- Volume
- 76
- Issue
- 18
- Pages
- 2076-2085
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W3095588466
- Cited by
- 97
- References
- 24
- Citations by year
- 2026: 5 · 2025: 16 · 2024: 13 · 2023: 15 · 2022: 23 · 2021: 22 · 2020: 3
- FWCI
- 9.75
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion, public-domain)
- PubMed (publishedVersion)
- Spiral (Imperial College London) (submittedVersion, cc-by-nc-nd)
- UNSWorks (University of New South Wales, Sydney, Australia) (submittedVersion, cc-by-nc-nd)
- Funders
- Pfizer
- Yale University
- Mitsubishi Tanabe Pharma Corporation
- Abbott Diagnostics
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Keywords
- canagliflozin, NT-proBNP, heart failure, type 2 diabetes, SGLT2 inhibitors, cardiovascular risk, heart failure hospitalization, cardiovascular mortality, all-cause mortality, CANVAS trial, mediation analysis, biomarkers, renal outcomes, cardiovascular outcomes, prognostic factors
- MeSH terms
- Canagliflozin, Sodium-Glucose Transporter 2 Inhibitors, Heart Disease Risk Factors, Aged, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Female, Humans, Male, Middle Aged, Peptide Fragments, Biomarkers, Treatment Outcome, Natriuretic Peptide, Brain, Risk Reduction Behavior
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