GLP-1 drugs tirzepatide and semaglutide provide protection for heart health
Mass General Brigham
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.
Additional links:
- GLP-1 Drugs Reduce Risk of Death and Hospitalization in Patients with Heart Failure
- In JAMA: Semaglutide and Tirzepatide in Patients With Heart Failure With Preserved Ejection Fraction
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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About Mass General Brigham
Mass General Brigham is an integrated academic health care system, uniting great minds to solve the hardest problems in medicine for our communities and the world. Mass General Brigham connects a full continuum of care across a system of academic medical centers, community and specialty hospitals, a health insurance plan, physician networks, community health centers, home care, and long-term care services. Mass General Brigham is a nonprofit organization committed to patient care, research, teaching, and service to the community. In addition, Mass General Brigham is one of the nation’s leading biomedical research organizations with several Harvard Medical School teaching hospitals. For more information, please visit massgeneralbrigham.org.
Journal
Nature Medicine
Method of Research
Randomized controlled/clinical trial
Subject of Research
People
Article Title
Cardiovascular outcomes of semaglutide and tirzepatide for patients with type 2 diabetes in clinical practice
Article Publication Date
9-Nov-2025
COI Statement
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.
Obesity drugs improve heart health: Study shows additional benefits of semaglutide and tirzepatide
- Database study compares protective effect of new GLP-1-based drugs in cardiovascular risk patients
- Evident heart benefits beyond weight loss
- Only few differences in effectiveness between semaglutide and tirzepatide for heart health
Injectable weight-loss drugs can reduce the risk of serious cardiovascular events for people with type 2 diabetes. Researchers at the Technical University of Munich (TUM) and Harvard Medical School have demonstrated this in using insurance claims data. They found that semaglutide and tirzepatide – marketed as Ozempic and Mounjaro – reduced the risk of serious cardiovascular events by up to 18 percent.
The study, published in Nature Medicine, analyzed a large dataset from US health insurers. "Those data are collected in routine clinical care and can be used for research. They allow us to answer a broad range of relevant questions efficiently. Importantly, we are studying patients who reflect everyday clinical practice – unlike the highly selected participants typically enrolled in randomized trials,” says Dr. Nils Krüger, first author of the study and a resident physician at the Department of Cardiovascular Diseases at the TUM University Hospital German Heart Center.
Both substances provide cardioprotective effects
The study demonstrates clear cardiovascular benefits for high-risk patients with type 2 diabetes. Compared with sitagliptin, a diabetes drug shown in previous studies to have no cardiovascular benefit, semaglutide reduced the risk of stroke and heart attack by 18 percent. Tirzepatide lowered the combined risk of stroke, heart attack, and death by 13 percent compared to dulaglutide, a GLP-1 drug that has been in clinical use for several years.
"Both substances have a cardioprotective effect. Our data show that the benefits emerge from early on, indicating that the effect goes beyond weight loss alone," says Dr. Krüger. The exact mechanisms driving this protective effect are still unclear.
As the two GLP-1 drugs have only been available for a short time, there has been a lack of studies demonstrating cardiovascular benefits in addition to weight loss – especially those directly comparing tirzepatide and semaglutide. According to the researchers, such comparative data are urgently needed to better protect at-risk patients. The interdisciplinary team led by Dr. Krüger at TUM University Hospital German Heart Center, Harvard Medical School and Brigham and Women's Hospital aims to close this evidence gap.
Only minor differences between the two drugs
“According to the manufacturers’ claims, each one suggests its own product is more effective than the competitor’s at reducing cardiovascular risk," says Prof. Heribert Schunkert, Director of the Department of Cardiovascular Diseases at TUM University Hospital. “Our study, however, shows only small differences in heart outcomes between tirzepatide and semaglutide in the risk groups we analyzed.”
Dr. Nils Krüger adds: "We hope our findings will provide clarity to physicians about how these new medications perform in clinical practice. Our transparent study design is also intended to support open scientific discussion about whether and how modern GLP-1 drugs should become part of the standard therapeutic repertoire in cardiovascular medicine.”
Publication:
Krüger, N., Schneeweiss, S., Desai, R.J. Cardiovascular outcomes of semaglutide and tirzepatide for patients with type 2 diabetes in clinical practice. Nat Med (2025). DOI: 10.1038/s41591-025-04102-x
Further information:
- Recently, Dr. Krüger's team was able to show that treatment with semaglutide or tirzepatide can reduce health risks for people with heart failure with preserved ejection fraction by over 40 percent. The study has been published in the journal JAMA (PMID: 40886075).
- 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, RWE/11/25).
- This news item on tum.de: https://www.tum.de/en/news-and-events/all-news/press-releases/details/obesity-drugs-improve-heart-health
Journal
Nature Medicine
Method of Research
Data/statistical analysis
Subject of Research
People
Article Title
Cardiovascular outcomes of semaglutide and tirzepatide for patients with type 2 diabetes in clinical practice
Article Publication Date
9-Nov-2025
COI Statement
Dr 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. Dr 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. Dr 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
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