By Dr. Asnat Raziel, bariatric surgeon specializing in obesity treatment, metabolic health and healthy longevity; Director of the Multidisciplinary Center for Obesity Treatment, Assia Medical, Assuta Ramat HaChayal, Tel Aviv
Mounjaro and the heart: beyond weight loss
The link between Mounjaro and the heart is one of the hottest topics in obesity and diabetes medicine today. Heart disease is the leading cause of death worldwide, and both obesity and diabetes raise the risk. Four large real-world studies have now looked at what happens to the heart and blood vessels in people taking Mounjaro. The picture is encouraging: less heart failure, fewer strokes after heart surgery and lower mortality. However, in a direct comparison with Ozempic, the heart benefit of the two drugs turned out to be similar.
Background: what the controlled trials already showed
Mounjaro contains tirzepatide, which acts on two gut hormones, GLP-1 and GIP. In the controlled SURPASS-CVOT trial, Mounjaro was compared with dulaglutide (Trulicity), an older GLP-1 drug with proven heart protection. Mounjaro proved no worse than dulaglutide. The hazard ratio for major cardiovascular events was 0.92 (confidence interval 0.83 to 1.01). Following the trial, the FDA also approved Mounjaro to lower the risk of heart attack and stroke. I described this in my article The SURPASS-CVOT trial: Mounjaro, the heart and the new FDA approval. I also explain what this approval does and doesn’t mean for patients.
Two terms worth knowing
MACE stands for major adverse cardiovascular events. It usually includes heart attack, stroke and death. The HR, or hazard ratio, compares the rate of events between two groups. A value of 1 means equal risk. A value below 1 points to lower risk in the treated group, while a value above 1 points to higher risk.
Study one: Mounjaro vs. Ozempic in people with diabetes
The first study, published in Nature Medicine, was carried out at Harvard University. The researchers used US insurance data on patients with type 2 diabetes and obesity from 2018 to 2025. First, they recreated two well-known controlled trials to make sure their method produced similar results. Then they directly compared 297,842 patients who started either Mounjaro or semaglutide, the active ingredient in Ozempic.
The results
In the head-to-head comparison, the risk of a major cardiovascular event in the first year was 1.3% in both groups. The hazard ratio was 1.06, with a confidence interval of 0.95 to 1.18. In other words, there was no difference between the drugs. The risk of heart attack, stroke and death, each on its own, was also similar. The researchers concluded that, when it comes to Mounjaro and the heart, the benefit in routine care is similar to that of semaglutide. For semaglutide’s own trial data, see my article on Wegovy for heart patients.
That said, there was a hint of a small advantage for Mounjaro in heart failure (HR 0.91, confidence interval 0.81 to 1.01). Still, the confidence interval included the possibility of no difference at all, so this finding is not conclusive. In addition, both drugs showed a benefit compared with older medications. Semaglutide reduced heart attacks and strokes compared with sitagliptin (HR 0.82). Likewise, Mounjaro showed a similar trend against dulaglutide (HR 0.87). I wrote about the heart protection of Wegovy in my article The SELECT trial: not just weight loss, Wegovy protects the heart.
Mounjaro and the heart: preventing heart failure in obesity
The second study, published in the European Journal of Preventive Cardiology, asked whether Mounjaro prevents heart failure. In heart failure, the heart does not pump blood efficiently, and obesity is one of its main causes. The researchers used TriNetX, a database that pools medical records from many centers around the world.
The study included adults with a BMI above 30, from January 2022 to June 2025. The researchers compared 190,513 patients who took Mounjaro with 190,513 similar patients who did not. Over one year, Mounjaro was linked to a 47% lower risk of new heart failure (HR 0.53). It was also linked to a lower risk of death from any cause (HR 0.31), hospital admission (HR 0.46) and major cardiovascular events (HR 0.55).
It is important to remember that the comparison was against patients who did not take the drug, not against another active treatment. This kind of comparison is especially sensitive to hidden differences between the groups. For that reason, the researchers call for prospective studies to confirm the findings.
Study three: Mounjaro and the heart after bypass surgery
The third study, published in Cardiovascular Drugs and Therapy, looked at a particularly high-risk group: people with diabetes who had coronary bypass surgery (CABG). It also drew on the TriNetX database and included patients who had surgery between 2022 and 2024. After statistical matching, the researchers compared 3,667 Mounjaro patients with 3,667 semaglutide patients.
Here are the main results, Mounjaro vs. semaglutide:
- Cerebrovascular disease, meaning disease of the blood vessels in the brain: 11.8% vs. 17.5%.
- Cerebral infarction (ischemic stroke): 4.6% vs. 7.3%.
- Blockage of blood vessels in the brain without infarction: 6.8% vs. 10.4%.
- Heart attack: 7.0% vs. 10.8%.
- Readmission to hospital within 3 years: 16.4% vs. 23.4%.
- Death from any cause within 3 years: 1.9% vs. 4.7%.
The brain findings remained significant even after statistical correction for multiple comparisons. By contrast, some of the heart findings were significant only at certain time points. The researchers stated that they received no funding for the study. For people who have already had a heart attack, see my article on GLP-1 treatment after a heart attack.
Study four: Mounjaro and the heart in diabetes with kidney disease
The fourth study, published in Nephrology Dialysis Transplantation, looked at people with diabetes, chronic kidney disease and excess weight. The researchers compared semaglutide, Mounjaro and bariatric surgery with a control group. The control group took a DPP-4 inhibitor, a drug that does not affect weight.
The Mounjaro group included 4,211 patients. Compared with the control group, Mounjaro was linked to a 24% lower risk of heart attack and stroke. The risk of death from any cause was also lower (HR 0.47), and the risk of end-stage kidney failure fell by 42%. Semaglutide and bariatric surgery were also linked to lower risk.
Mounjaro and the heart: what these studies cannot prove
All four studies are retrospective real-world studies. They show an association, not necessarily cause and effect. First, even after statistical matching, unmeasured differences between the groups may remain. Second, the data come from medical records and insurance claims, which may contain recording errors. Third, actual treatment time was relatively short: in the Nature Medicine study, patients were treated for about six months on average. Finally, most of the studies were done in the United States.
Even so, the Nature Medicine study stands out for its quality. The researchers registered their study plan in advance. They also tested their method against controlled trials before running the head-to-head comparison. Another real-world comparison of the two drugs is the STEER study, which I reviewed separately.
Mounjaro and the heart: what this means for you
If you have obesity or diabetes, and especially existing heart disease, medication can be part of protecting your heart. The data show that both Mounjaro and semaglutide protect the heart. Moreover, in a direct comparison in people with diabetes, the benefit was similar. So the choice between them depends on other factors: your weight loss goal, blood sugar control, side effects and availability. I wrote about tailoring treatment in my article Mounjaro (tirzepatide): how it works, what the trials found and who it is for.
A few practical steps:
- Know your risk factors: blood pressure, LDL cholesterol, blood sugar and smoking.
- Don’t stop heart or cholesterol medications when you start obesity treatment without talking to your doctor.
- Build in regular exercise, good sleep and a Mediterranean diet.
- If you have had a heart event or heart surgery, ask your cardiologist which treatment is right for you.
The bottom line
Real-world studies strengthen the link between Mounjaro and the heart. They point to a lower risk of heart failure in obesity, fewer brain events after bypass surgery, and fewer heart attacks and strokes in diabetes with kidney disease. On the other hand, in the most direct and rigorous comparison, Mounjaro and semaglutide showed a similar heart benefit. Ultimately, protecting your heart starts with a personalized choice and consistent long-term treatment.
The information in this article is general information only and is not a substitute for personal medical advice. Before starting or changing any treatment, consult your doctor.
References
Cardiorenal outcomes of weight loss interventions in people with CKD and type 2 diabetes
