An Observational Study of Cardiovascular Outcomes of Tirzepatide vs Glucagon-Like Peptide-1 Receptor Agonists
Open accessAbstract
BACKGROUND: While cardiovascular benefits of tirzepatide, a glucose-dependent insulinotropic peptide/glucagon-like peptide-1 receptor agonist in patients with type 2 diabetes mellitus (T2DM), and its comparative effectiveness vs glucagon-like peptide-1 receptor agonists (GLP-1RAs) is studied in randomized controlled trials, real-world outcomes may provide critical insights. OBJECTIVES: The purpose of this study was to examine the cardiovascular benefits of tirzepatide vs GLP-1RA in people living with overweight or obesity, with T2DM, age ≥40 years, and pre-existing ischemic heart disease (IHD). METHODS: receiving either tirzepatide or GLP-1RA were identified and divided into 2 groups (tirzepatide vs GLP-1RA). After propensity score matching, Cox-proportional HRs were used to compare efficacy and safety outcomes during 1-year follow-up. RESULTS: Among 47,719 adults, 753 received tirzepatide, and 46,966 were on GLP-1RA. After propensity score matching, each group had 751 adults (mean age 59.9 ± 8.9 years, 46.5% females, 74.8% White adults in the tirzepatide group). Treatment with tirzepatide was associated with lower primary composite outcomes of acute myocardial infarction, ischemic stroke, and all-cause mortality (HR: 0.60, 95% CI: 0.43-0.84, P < 0.001). Individually, acute myocardial infarction (HR: 0.59, 95% CI: 0.38-0.91) and all-cause mortality (HR: 0.35, 95% CI: 0.14-0.88, P = 0.001) were also found to be favorable in the tirzepatide group. CONCLUSIONS: , and pre-existing IHD.
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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: <i>post-hoc</i> analysis of the SURMOUNT-5 trial (2025) · cites this paper as [40]
The Results (Subgroup analysis; page unavailable) report a lower composite cardiovascular risk with tirzepatide in a real-world comparison against semaglutide or liraglutide combined. The paper does not report a semaglutide-only cardiovascular comparison, so it supports the direction of the claim but not its specific comparator. (LLM, conf=0.86)
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Self-citation
- Authors
- Dani, S. S., Makwana, B., Khadke, S., Kumar, A., Jhund, P., Nasir, K., Sattar, N., Al-Kindi, S., Fonarow, G., Butler, J., Bhatt, D. L., Kosiborod, M. N., Nohria, A., & Ganatra, S.
- Affiliations
- Lahey Hospital and Medical Center (US)
- Cleveland Clinic (US)
- University of Glasgow (GB)
- Houston Methodist (US)
- University of California, Los Angeles (US)
- Baylor Scott & White Research Institute (US)
- Icahn School of Medicine at Mount Sinai (US)
- University of Missouri–Kansas City (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Ganatra, Sarju
- ORCID
- Venue
- JACC: Advances
- Publisher
- Elsevier BV
- Published
- 2025-05
- Volume
- 4
- Issue
- 5
- Pages
- 101740
- ISSN
- 2772-963X (ISSN-L)
- PMC
- PMC12235410
- OpenAlex
- W4410806707
- Cited by
- 30
- References
- 37
- Citations by year
- 2026: 20 · 2025: 10
- FWCI
- 20.46
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- JACC Advances (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion, cc-by-sa)
- 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, GLP-1 receptor agonists, type 2 diabetes, cardiovascular outcomes, acute myocardial infarction, ischemic stroke, all-cause mortality, ischemic heart disease, obesity, real-world effectiveness, GIP/GLP-1 dual agonist
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