Researchers led by Mass General Brigham and the Technical University of Munich report that tirzepatide and semaglutide are associated with significant reductions in heart attacks, strokes and death among adults with type 2 diabetes at elevated cardiovascular risk. Drawing on nearly one million insurance records, the Nature Medicine analysis finds strong and early heart protection from both GLP‑1–based drugs, with only modest differences between them.
A large real‑world study published in Nature Medicine and presented at the American Heart Association Scientific Sessions 2025 reports that the GLP‑1–based medicines tirzepatide and semaglutide are linked to strong cardiovascular benefits in adults with type 2 diabetes.
According to materials from Mass General Brigham and the Technical University of Munich, the research team analyzed U.S. national health insurance claims from nearly one million adults with type 2 diabetes who were at higher risk for heart‑related complications. The investigators compared outcomes among people treated with tirzepatide (sold as Mounjaro and Zepbound), semaglutide (marketed as Ozempic and Wegovy), and other diabetes drugs.
Earlier randomized trials had already shown that semaglutide can lower the risk of major cardiovascular events, such as heart attacks and strokes, in high‑risk patients. What was less certain was whether tirzepatide, another widely used therapy for type 2 diabetes and obesity, provides similar heart protection.
In the new study, semaglutide was compared with sitagliptin, a diabetes medication regarded as having a neutral effect on cardiovascular outcomes. Semaglutide reduced the combined risk of heart attack and stroke by 18 percent relative to sitagliptin, the researchers report.
Tirzepatide was evaluated against dulaglutide, an older GLP‑1 receptor agonist used for type 2 diabetes. Treatment with tirzepatide lowered the combined risk of heart attack, stroke and death from any cause by 13 percent compared with dulaglutide, according to the study.
“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 first author Nils Krüger, MD, a research fellow in the Division of Pharmacoepidemiology and Pharmacoeconomics in the Mass General Brigham Department of Medicine, in a statement released by Mass General Brigham.
Krüger highlighted the advantages of using real‑world health data in addition to traditional randomized trials. “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,” he said.
The authors note that drug manufacturers have publicized database analyses suggesting their own products outperform competitors on cardiovascular risk. However, in this independently led analysis, direct comparisons between tirzepatide and semaglutide revealed only small differences in cardiovascular protection for populations at elevated risk, reinforcing that both agents appear to provide meaningful benefit.
“We hope that our study will help clinicians better understand how these new medications work in clinical practice,” said senior author Shirley Wang, PhD, an associate epidemiologist in the same division at Mass General Brigham. She added that the group relied on transparent, open‑science practices, including pre‑registration of a public protocol and shared analytic code, to support scientific discussion.
While the data point to early and substantial reductions in cardiovascular events, the exact biological pathways by which tirzepatide and semaglutide protect the heart remain unclear and will require further study. The work was funded by the U.S. National Institutes of Health and the German Heart Foundation, according to the study sponsors.
