Tirzepatide Shows Lower CV Risk vs. Dulaglutide in Type 2 Diabetes

For adults with type 2 diabetes and established cardiovascular disease, a new analysis suggests tirzepatide may offer a cardiovascular edge over dulaglutide, though it appears comparable to semaglutide. The findings, published in Diabetes Care on March 23, 2026, add to a growing body of evidence examining the cardiovascular benefits of different GLP-1 receptor agonist-based therapies.

Tirzepatide and Cardiovascular Risk: What the Study Found

Researchers analyzed data from the Optum deidentified Clinformatics Data Mart Database, focusing on individuals aged 40 and older with both type 2 diabetes and pre-existing atherosclerotic cardiovascular disease (ASCVD). The study compared outcomes for those prescribed tirzepatide (Mounjaro, Eli Lilly), dulaglutide (Trulicity, Eli Lilly), and semaglutide (Ozempic, Novo Nordisk) between June 2022 and December 2024. The primary outcome measured was a composite of major adverse cardiovascular events (MACE) – nonfatal myocardial infarction (heart attack), nonfatal stroke, or all-cause mortality.

The analysis revealed that individuals taking tirzepatide experienced a 20% lower risk of MACE compared to those on dulaglutide. Specifically, the incidence rate was 31.3 per 1,000 person-years for tirzepatide users versus 39.4 per 1,000 person-years for dulaglutide users (Hazard Ratio = 0.8, 95% Confidence Interval: 0.65-0.99). Notably, the study did not find a significant difference in cardiovascular risk between those using tirzepatide, and semaglutide.

“The core clinical implication is that clinicians and patients may prefer tirzepatide or semaglutide over dulaglutide to reduce adverse CV outcomes or death in persons with type 2 diabetes and CVD,” explained John W. Ostrominski, MD, MPH, a fellow in cardiovascular and obesity medicine at Brigham and Women’s Hospital and Harvard Medical School, in comments to Healio.

Understanding the Findings in Context

This study builds upon previous research, including the SURPASS-CVOT trial. As previously reported by Healio, SURPASS-CVOT demonstrated that tirzepatide was non-inferior to dulaglutide in reducing MACE, but also showed a trend towards lower all-cause mortality with tirzepatide. The current observational study reinforces this finding regarding mortality risk, with the tirzepatide group exhibiting a 40% lower risk of all-cause mortality compared to the dulaglutide group (HR = 0.6; 95% CI, 0.43-0.83).

It’s important to note that this study utilized a real-world database, which offers valuable insights into treatment effects outside of the controlled environment of a clinical trial. However, observational studies are susceptible to biases. Researchers employed propensity score matching to mitigate confounding factors, but residual confounding cannot be entirely ruled out. The study also observed that, on average, patients discontinued semaglutide or tirzepatide therapy after approximately 6 to 8 months, potentially limiting the ability to detect long-term differences in cardiovascular outcomes.

GLP-1 Receptor Agonists and Cardiovascular Health: A Broader Perspective

GLP-1 receptor agonists, like tirzepatide, dulaglutide, and semaglutide, are a class of medications initially developed for the treatment of type 2 diabetes. They work by mimicking the effects of the naturally occurring GLP-1 hormone, which stimulates insulin release, suppresses glucagon secretion, and slows gastric emptying. Beyond their glucose-lowering effects, these medications have demonstrated cardiovascular benefits in several clinical trials.

The mechanisms underlying these cardiovascular benefits are complex and not fully understood. Potential mechanisms include improvements in blood pressure, lipid profiles, inflammation, and weight loss. Recent research has also highlighted the cardiovascular benefits of semaglutide (marketed as Wegovy for weight management) in individuals with obesity and cardiovascular risk factors, even in the absence of diabetes.

What Does This Mean for Patients?

The findings from this study, coupled with existing evidence, suggest that tirzepatide and semaglutide may be preferable options for individuals with type 2 diabetes and established cardiovascular disease compared to dulaglutide, with the goal of reducing cardiovascular events and mortality. However, treatment decisions should be individualized, taking into account patient-specific factors such as comorbidities, medication costs, and preferences. It is crucial for patients to discuss the potential benefits and risks of each medication with their healthcare provider.

Future Research Directions

Even as this study provides valuable insights, further research is needed to clarify the comparative effectiveness of different GLP-1 receptor agonists. Specifically, studies comparing semaglutide and tirzepatide directly are warranted. Research should focus on identifying which patient subgroups are most likely to benefit from each medication and on understanding the long-term effects of these therapies on cardiovascular outcomes. Investigating the impact of these medications on other cardiometabolic outcomes, such as heart failure and kidney disease, is also crucial.

Ongoing surveillance and data analysis will continue to refine our understanding of the cardiovascular effects of GLP-1 receptor agonists and inform clinical practice guidelines. Patients and healthcare providers should stay informed about the latest research and recommendations from organizations like the American Diabetes Association and the American Heart Association.