GLP-1 Drugs Tirzepatide and Semaglutide Provide Protection for Heart Health
Mass General Brigham researchers used real-world data to conduct a head-to-head study to investigate cardioprotective effects, finding both medications reduced risk.
A new study from Mass General Brigham provides head-to-head evidence comparing the cardioprotective effects of tirzepatide and semaglutide. The researchers found both medications reduced the risk of heart attack, stroke, and death from any cause. The study is published in Nature Medicine and results were presented simultaneously at the American Heart Association Scientific Sessions 2025.
Previous research shows that semaglutide protects against cardiovascular events like heart attack or stroke. But it wasn’t clear if tirzepatide, also commonly prescribed for type 2 diabetes, has the same cardiovascular benefits.
Researchers used national claims databases to compare the cardiovascular outcomes of nearly one million adults taking tirzepatide, semaglutide, or other medications for type 2 diabetes.
“Randomized controlled trials are often considered the reference standard in the medical evidence generation process. However, not all questions can be answered using this time- and resource-intensive method,” said first author Nils Krüger, MD, a research fellow in the Division of Pharmacoepidemiology and Pharmacoeconomics in the Mass General Brigham Department of Medicine. “Data generated in clinical practice and used secondarily for research allow us to address a wide range of clinically relevant questions time- and resource-effectively—when applied correctly. Moreover, we can study patients who reflect the reality of everyday clinical care, in contrast to the highly selected participants of randomized experiments.”
The study demonstrated a cardiovascular benefit for patients at risk for adverse cardiovascular events who had type 2 diabetes. Compared with sitagliptin, a diabetes drug that has shown neutral effects on cardiovascular outcomes, semaglutide reduced the risk of stroke and heart attack by 18 percent. Treatment with tirzepatide lowered the risk of stroke, heart attack, and death by 13 percent compared to dulaglutide, another GLP-1 receptor agonist that has been available for many years.
“Both drugs show strong cardioprotective effects. Our data also indicate that these benefits occur early, suggesting that their protective mechanisms go beyond weight loss alone,” said Krüger. The exact biological mechanisms underlying these protective effects remain unknown.
Because these medications have only recently become available, studies confirming their cardioprotective mechanisms—particularly those directly comparing the two dominant GLP-1 agents, tirzepatide and semaglutide—are still lacking.
“According to recently presented database analyses by the respective manufacturers, each company’s own drug appears to reduce cardiovascular risk much more effectively than the competitor’s,” said Krüger. “However, our study found only small differences between tirzepatide and semaglutide in cardiovascular protection among populations at risk of adverse events, underscoring that both agents provide protective benefit and could be integrated into clinical cardiovascular practice.”
“We hope that our study will help clinicians better understand how these new medications work in clinical practice. Our transparent and open science practices, including pre-registration of a public protocol and shared analytic code, are designed to support scientific discussion,” said last author Shirley Wang, PhD, an associate epidemiologist in the Division of Pharmacoepidemiology and Pharmacoeconomics in the Mass General Brigham Department of Medicine.
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Authorship: In addition to Krüger, Mass General Brigham authors include Sebastian Schneeweiss, Rishi J. Desai, Sushama Kattinakere Sreedhara, Anna R. Kehoe, Kenshiro Fuse, Georg Hahn, and Shirley V. Wang. Additional authors include Heribert Schunkert.
Disclosures: Schneeweiss reported personal fees from Aetion Inc, a software-enabled analytics company, and grants from Bayer, UCB, and Boehringer Ingelheim to Brigham and Women’s Hospital outside the submitted work. Schunkert reported personal fees from AstraZeneca, Bayer Vital GmbH, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, MSD, Novartis, Pharmacosmos, Sanofi, Servier, Synlab, Amgen, and Amarin outside the submitted work. Wang reported personal fees from MITRE, a federally funded research and development center for the Centers for Medicare & Medicaid Services and personal fees from Cytel Inc during the conduct of the study. No other disclosures were reported.
Funding: This work was funded by the National Institutes of Health (R01-HL141505, R01-AR080194) and the German Heart Foundation (S/02/24, SRF-HF/24).
Paper cited: Krüger N et al. “Cardiovascular outcomes of semaglutide and tirzepatide for patients with type 2 diabetes in clinical practice” Nature Medicine DOI: 10.1038/s41591-025-04102-x
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