Meta‐analysis of risk of major adverse cardiovascular events in adults with type 2 diabetes treated with bexagliflozin
Open accessAbstract
Aim: To explore the risk of major adverse cardiovascular events (MACE) associated with exposure to bexagliflozin. Methods: The analysis included 4090 participants with type 2 diabetes (T2D) enrolled in nine phase 2 and 3 double‐blind randomized controlled trials. All potential MACE were adjudicated by a blinded committee. The primary endpoint for the meta‐analysis was the hazard ratio (HR) for the time to first occurrence of non‐fatal stroke, non‐fatal myocardial infarction (MI), cardiovascular (CV) death or hospitalization for unstable angina (MACE+), tested for non‐inferiority to a ratio of 1.8. The secondary endpoints were time to first occurrence of (i) non‐fatal stroke, non‐fatal MI or CV death (MACE), tested for non‐inferiority to a ratio of 1.3; and (ii) CV death or hospitalization for heart failure, tested for superiority. Results: The HR for the primary endpoint of MACE+ was 0.80 (95% confidence interval [CI] 0.58, 1.09), which fulfilled the non‐inferiority objective with a P value of less than 0.0001. Non‐inferiority for the first key secondary endpoint of MACE was also shown (HR = 0.82; 95% CI 0.59, 1.13; P = 0.0023). Superiority for time to CV death or first hospitalization for heart failure was not shown. Conclusions: Bexagliflozin did not increase the risk of MACE in participants with T2D when compared with placebo or active control. Both the preapproval and postapproval thresholds for CV safety were met and bexagliflozin has been approved by the US Food and Drug Administration.
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Cardiovascular outcome trials of ertugliflozin and bexagliflozin have not demonstrated evidence of cardiovascular risk reduction.
“Cardiovascular outcome trials of ertugliflozin and bexagliflozin have not demonstrated evidence of cardiovascular risk reduction (249,250).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [250]
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- Authors
- McMurray, J. J. V., Solomon, S. D., Lock, J. P., Massaro, J. M., Zhu, F., Zhou, W., Skali, H., Lewis, E. F., Freeman, M. W., & Halvorsen, Y. C.
- Affiliations
- University of Glasgow (GB)
- Brigham and Women's Hospital (US)
- University of Massachusetts Chan Medical School (US)
- Boston University (US)
- Hopkins Consulting LLC Philadelphia Pennsylvania USA
- Stanford Health Care (US)
- Massachusetts General Hospital (US)
- Corresponding author
- Freeman, Mason W.
- ORCID
- Venue
- Diabetes, Obesity and Metabolism
- Publisher
- Wiley
- Published
- 2023-12-27
- Volume
- 26
- Issue
- 3
- Pages
- 971-979
- ISSN
- 1462-8902 (ISSN-L)
- 1463-1326
- OpenAlex
- W4390343105
- Cited by
- 9
- References
- 22
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4
- FWCI
- 1.85
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetes Obesity and Metabolism (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- 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 › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- bexagliflozin, type 2 diabetes, major adverse cardiovascular events, cardiovascular safety, non-inferiority, myocardial infarction, stroke, cardiovascular mortality, heart failure hospitalization, SGLT2 inhibitors
- MeSH terms
- Adult, Cardiovascular Diseases, Cardiovascular System, Diabetes Mellitus, Type 2, Heart Failure, Humans, Hypoglycemic Agents, Myocardial Infarction, Pyrans, Randomized Controlled Trials as Topic, Stroke
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