Cardiovascular outcomes with tirzepatide versus dulaglutide in type 2 diabetes
Open accessAbstract
BACKGROUND: Tirzepatide, a dual incretin agonist of the glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide receptors, has favorable effects on glycemic control and body weight. The effects on cardiovascular outcomes are uncertain. METHODS: We conducted an active-comparator-controlled, double-blind, noninferiority trial in which patients with type 2 diabetes and atherosclerotic cardiovascular disease were randomly assigned in a 1:1 ratio to receive a weekly subcutaneous injection of tirzepatide (up to 15 mg) or dulaglutide (1.5 mg), an agent that has been shown to reduce the incidence of cardiovascular events. The primary end point was a composite of death from cardiovascular causes, myocardial infarction, or stroke and was tested for noninferiority of tirzepatide to dulaglutide with a margin of 1.05 for the upper limit of the 95.3% confidence interval for the hazard ratio. An upper limit of less than 1.00 was considered to indicate superiority of tirzepatide to dulaglutide. RESULTS: A total of 13,299 patients underwent randomization; 134 were subsequently excluded because they did not meet inclusion criteria. The modified intention-to-treat population thus included 6586 patients in the tirzepatide group and 6579 in the dulaglutide group. The mean (±SD) age of the patients was 64.1±8.8 years, 29.0% were women, the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 32.6±5.5, the mean glycated hemoglobin level was 8.4±0.9%, and the mean duration of diabetes was 14.7±8.8 years. A primary end-point event occurred in 801 patients (12.2%) in the tirzepatide group and 862 (13.1%) in the dulaglutide group (hazard ratio, 0.92; 95.3% confidence interval, 0.83 to 1.01; P = 0.003 for noninferiority; P = 0.09 for superiority). The incidence of adverse events appeared to be similar in the two groups, although more gastrointestinal adverse events were observed in the tirzepatide group. CONCLUSIONS: Among patients with type 2 diabetes and atherosclerotic cardiovascular disease, tirzepatide was noninferior to dulaglutide with respect to a composite of death from cardiovascular causes, myocardial infarction, or stroke. (Funded by Eli Lilly; SURPASS-CVOT ClinicalTrials.gov number, NCT04255433.).
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The SURPASS-CVOT trial showed comparable cardiovascular outcomes with tirzepatide relative to dulaglutide.
“showed comparable cardiovascular outcomes with dual GLP-1/GIP receptor agonism relative to established GLP-1 RAs (dulaglutide)”
From Weight maintenance after discontinuation of GLP-1 therapies (2026) · cites this paper as [30]
Large cardiovascular outcome trials in high-risk patients with type 2 diabetes have consistently demonstrated reductions in major adverse cardiovascular events (MACE) with GLP-1 RAs.
“Large cardiovascular outcome trials in high-risk patients with type 2 diabetes have consistently demonstrated reductions in major adverse cardiovascular events (MACE) with GLP-1 RAs.”
From Weight maintenance after discontinuation of GLP-1 therapies (2026) · cites this paper as [30]
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References 31 · Cited by 223
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- Authors
- Nicholls, S. J., Pavo, I., Bhatt, D. L., Buse, J. B., Del Prato, S., Kahn, S. E., Lincoff, A. M., McGuire, D. K., Miller, D., Nauck, M. A., Nishiyama, H., Nissen, S. E., Sattar, N., Weerakkody, G., Wiese, R. J., Zinman, B., Zoungas, S., Basile, J., Davies, M. J., Giorgino, F., Kellerer, M., Ji, L., Varkonyi, T., Menon, V., Broder, J. C., Herschtal, A., & D’Alessio, D.
- Affiliations
- Monash University (AU)
- Eli Lilly (United States) (US)
- Icahn School of Medicine at Mount Sinai (US)
- University of North Carolina at Chapel Hill (US)
- Interdisciplinary Research Center “Health Science,” Sant’Anna School of Advanced Studies, Pisa, Italy
- University of Washington (US)
- Cleveland Clinic Lerner College of Medicine (US)
- Parkland Health & Hospital System (US)
- Universitätsmedizin Greifswald (DE)
- Cleveland Clinic (US)
- University of Glasgow (GB)
- Mount Sinai Hospital (CA)
- Medical University of South Carolina (US)
- University of Leicester (GB)
- University of Bari Aldo Moro (IT)
- Universitätsklinikum Tübingen (DE)
- Peking University People's Hospital (CN)
- Department of Internal Medicine, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary
- Duke Medical Center (US)
- ORCID
- Nicholls, Stephen J.
- Pavo, Imre
- Bhatt, Deepak L.
- Buse, John B.
- Kahn, Steven E.
- Lincoff, A. Michael
- McGuire, Darren K.
- Miller, Debra
- Nauck, Michael A.
- Nishiyama, Hiroshi
- Nissen, Steven E.
- Sattar, Naveed
- Weerakkody, Govinda
- Wiese, Russell J.
- Zinman, Bernard
- Zoungas, Sophia
- Davies, Melanie J.
- Giorgino, Francesco
- Kellerer, Monika
- Ji, Linong
- Menon, Venu
- Broder, Jonathan C.
- Herschtal, Alan
- D’Alessio, David
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2025-12-18
- Volume
- 393
- Issue
- 24
- Pages
- 2409-2420
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W4417497606
- Cited by
- 223
- References
- 31
- Citations by year
- 2026: 222 · 2025: 1
- FWCI
- 151.47
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- SZTE Publicatio Repozitórium (University of Szeged) (acceptedVersion, other-oa)
- CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion)
- Funders
- Eli Lilly and Company
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Keywords
- tirzepatide, dulaglutide, type 2 diabetes, cardiovascular outcomes, non-inferiority, atherosclerotic cardiovascular disease, GLP-1 receptor agonists, GIP receptor agonist, myocardial infarction, stroke, cardiovascular mortality, gastrointestinal adverse effects, nonalcoholic steatohepatitis
- MeSH terms
- Glucagon-Like Peptide-1 Receptor Agonists, Tirzepatide, Aged, Blood Glucose, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Double-Blind Method, Glucagon-Like Peptides, Female, Glycated Hemoglobin, Humans, Immunoglobulin Fc Fragments, Injections, Subcutaneous, Male, Middle Aged, Recombinant Fusion Proteins, Treatment Outcome, Intention to Treat Analysis
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