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223-OR: Emulation of the Study of Tirzepatide Compared with Dulaglutide on Major Cardiovascular Events in Participants with Type 2 Diabetes (SURPASS-CVOT)
Abstract
Introduction and Objective: SURPASS-CVOT is an ongoing, randomized, active-controlled trial evaluating the effect of tirzepatide vs. dulaglutide on major adverse cardiovascular events (MACE) in people with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD). We aimed to emulate the SURPASS-CVOT trial using insurance claims data. Methods: Using claims from a private health plan (06/2022 to 08/2024), we identified 15,775 pairs of 1:1 propensity score (PS)-matched adults initiating tirzepatide or dulaglutide, stratified by baseline SGLT2i use. Our primary outcome was MACE (myocardial infarction, stroke, or mortality). We estimated hazard ratios (HRs) and 95% confidence intervals (CI), adjusting for 125 covariates. We also conducted HbA1c-adjusted analyses among those with HbA1c values (54% of population). Results: Over a median follow up of ~6 months, tirzepatide was associated with a 37% reduction in MACE vs. dulaglutide (Table). Results were consistent in the HbA1c-adjusted analysis (HR, 0.77; 95% CI, 0.62 to 0.95) and, in both analyses, irrespective of SGLT2i use. Conclusion: In this observational study emulating SURPASS-CVOT, tirzepatide appeared superior to dulaglutide in preventing MACE events. This study may also inform the design and conduct of future observational studies evaluating GLP-1-based treatments. Disclosure: J. Ostrominski: None. J. Ortega-Montiel: None. H. Tesfaye: None. C. Alix: None. D.J. Wexler: Other Relationship; Novo Nordisk. J.M. Paik: None. E. Patorno: Research Support; National Institute of Diabetes and Digestive and Kidney Diseases, Patient-Centered Outcomes Research Institute, Food and Drug Administration (FDA), Boehringer-Ingelheim. Other Relationship; UpToDate.
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Studies have reported beneficial effects in cardiovascular outcomes in populations with type 2 diabetes.
“While studies have reported beneficial effects in cardiovascular outcomes in populations with T2D,19–23 data to understand the long-term health benefits, such as CVD risk reduction, in patients with obesity are limited.24,25”
From Tirzepatide compared with semaglutide and 10-year cardiovascular disease risk reduction in obesity: post-hoc analysis of the SURMOUNT-5 trial (2025) · cites this paper as [21]
The association between tirzepatide versus semaglutide and CVD risk reduction is consistent with previous real-world evidence studies.
“The association between tirzepatide vs. semaglutide and CVD risk reduction is consistent with previous real-world evidence studies.13,20,21,14,40”
From Tirzepatide compared with semaglutide and 10-year cardiovascular disease risk reduction in obesity: post-hoc analysis of the SURMOUNT-5 trial (2025) · cites this paper as [21]
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Mamas, M. A., Bays, H., Li, R., Upadhyay, N., Irani, T., Senyucel, C., Dunn, J. P., & Liu-Seifert, H. (2025) · European Heart Journal Open · doi:10.1093/ehjopen/oeaf117 · Cited by 24
“13,20,21,14,40 Based on this analysis, there is the potential that tirzepatide might have a benefit vs. semaglutide in the primary prevention of CVD events.”
Hsu, C., Hsuan, C., Liao, D., Chang, J. K.-J., Chang, A. J.-W., Hee, S., Lee, H.-L., & Teng, S. I. F. (2023) · Life · doi:10.3390/life13041024 · Cited by 11
Node, K., Batterham, R. L., Liu‐Seifert, H., Li, R., Yoshino, M., Oura, T., Tanizawa, Y., & Komuro, I. (2026) · Current Medical Research and Opinion · doi:10.1080/03007995.2026.2686052 · Cited by 1
Qazi, S., Zahid, M., Atif, E., Ilyas, A. F., Ali, M., Ali, U., Junaid, M., Fatima, E., Bibi, S., Ashraf, R. M. H., et al. (2026) · Healthcare · doi:10.3390/healthcare14070850
Metadata
- Authors
- OSTROMINSKI, J., ORTEGA-MONTIEL, J., TESFAYE, H., ALIX, C., WEXLER, D. J., PAIK, J. M., & PATORNO, E.
- Affiliations
- Boston, MA
- ORCID
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2025-06-20
- Volume
- 74
- Issue
- Supplement_1
- ISSN
- 0012-1797 (ISSN-L)
- OpenAlex
- W4411292316
- Cited by
- 3
- References
- 0
- Citations by year
- 2026: 2 · 2025: 1
- FWCI
- 2.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- 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 › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- tirzepatide, dulaglutide, type 2 diabetes, major adverse cardiovascular events, SGLT2 inhibitors, GLP-1 receptor agonists, atherosclerotic cardiovascular disease, myocardial infarction, stroke, mortality, HbA1c, health insurance claims, propensity score matching
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