A research team at Mass General Brigham has released new evidence directly comparing how well tirzepatide (Mounjaro, Zepbound) and semaglutide (Ozempic, Wegovy) protect the heart. According to the analysis, both medications lowered the chances of heart attack, stroke, and death from any cause. The study appears in Nature Medicine, and the findings were also presented at the American Heart Association Scientific Sessions 2025.
Earlier studies had already shown that semaglutide lowers the likelihood of major cardiovascular events such as heart attacks and strokes. What had remained uncertain was whether tirzepatide, another widely used treatment for type 2 diabetes, offers similar protection.
Large Real-World Dataset Offers New Clarity
To investigate this, researchers examined national health insurance claims and compared cardiovascular outcomes among nearly one million adults using tirzepatide, semaglutide, or other type 2 diabetes therapies.
"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."
Risk Reductions Seen in Both Medications
The results showed measurable cardiovascular benefits among people with type 2 diabetes who were at higher risk for heart-related complications. When compared with sitagliptin, a diabetes medication known to have a neutral effect on cardiovascular outcomes, semaglutide lowered the combined risk of heart attack and stroke by 18 percent. Tirzepatide produced a 13 percent reduction in the risk of heart attack, stroke, and death when compared with dulaglutide, another GLP-1 receptor agonist that has been on the market 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. Although the study highlights strong results, the biological pathways behind these heart-protective effects are still not fully understood.
Head-to-Head Comparisons Show Only Small Differences
Since these medications are relatively new, scientists continue to investigate how they protect the heart, especially in studies that directly compare tirzepatide and semaglutide. Krüger noted that "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." He added, "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.
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).