In a study of over 75,000 people with diabetes and heart disease, semaglutide reduced the risk of heart attacks, strokes, and cardiovascular death by 22% compared to dulaglutide.
22% lower risk of MACESemaglutide users had significantly fewer heart attacks, strokes, and cardiovascular deaths than dulaglutide users in this 75,000-person study
What the researchers found
Among 75,243 U.S. adults with type 2 diabetes and established atherosclerotic cardiovascular disease, semaglutide users had a 22% lower risk of major adverse cardiovascular events (MACE) compared to dulaglutide users (HR 0.78, 95% CI 0.70–0.87, p<0.001).
MACE incidence rates were 25.7 per 1,000 person-years for semaglutide versus 33.0 for dulaglutide. After entropy balancing to account for baseline differences, all standardized mean differences were below 0.1, indicating well-matched cohorts.
Why it matters
While both semaglutide and dulaglutide are GLP-1 receptor agonists approved for type 2 diabetes, clinicians have lacked direct head-to-head cardiovascular outcome data comparing them. This large real-world study fills that gap, suggesting semaglutide offers meaningfully better heart protection in patients who already have cardiovascular disease — a finding that could influence prescribing decisions for millions of high-risk patients.
The numbers in context
n=75,243 · HR 0.78 (95% CI 0.70–0.87) · p<0.001 · semaglutide MACE rate 25.7/1000 PY · dulaglutide MACE rate 33.0/1000 PY · 22% risk reduction
How the study worked
Retrospective cohort study using Optum's de-identified Clinformatics Data Mart (Medicare claims data) from January 2007 through September 2024. Included new initiators of semaglutide (n=42,007) or dulaglutide (n=33,236) aged 18+ with both type 2 diabetes and established atherosclerotic cardiovascular disease. Entropy balancing was used to match cohorts on baseline characteristics. Primary outcome was 3-point MACE (stroke, MI, CV death), analyzed with doubly robust Cox proportional hazard models.
Who was studied
U.S. Medicare enrollees aged 18+ with both type 2 diabetes and established atherosclerotic cardiovascular disease (mean age ~68-69 years)
What this study cannot tell us
As a retrospective claims-based study, it cannot establish causation and may be subject to residual confounding despite entropy balancing. Medicare claims data may not capture all cardiovascular events or deaths. The study cannot determine which specific dose of each drug patients received, and adherence patterns are unknown. It reflects a U.S. Medicare population, which may not generalize to younger or international populations.
How to read the evidence
Rated high because this is a large retrospective cohort study (n=75,243) with robust statistical methods including entropy balancing and doubly robust Cox models, though it falls short of a randomized controlled trial.
When this study was published
Published in 2026 with data through September 2024, this is among the most current real-world cardiovascular outcome comparisons between these two GLP-1 drugs.
The bigger picture
GLP-1 receptor agonists have gone from diabetes drugs to cardiovascular protectors, but they're not all equal. This study provides the strongest real-world evidence yet that semaglutide offers superior heart protection compared to dulaglutide, which could shift prescribing patterns and insurance formulary decisions for the millions of patients with both diabetes and heart disease.
Questions still open
- Is semaglutide's cardiovascular advantage due to greater weight loss, direct vascular effects, or both?
- Would the same advantage hold for patients without established cardiovascular disease?
- How does tirzepatide's cardiovascular profile compare to semaglutide in this high-risk population?
Common questions
Does this mean semaglutide is better than dulaglutide for everyone with diabetes?
What is MACE and why does it matter?
Read the original research
Comparison of cardiovascular outcomes between once-weekly semaglutide and dulaglutide in adults with type 2 diabetes and established atherosclerotic cardiovascular disease in the United States.
Diabetes, obesity & metabolism
Citation
Tan, Xi; Liang, Yuanjie; Xie, Lin; Harton, Joanna; Gutierrez, Cynthia; Muhammad, Chalak; Swift, Caroline; de Havenon, Adam. (2026). Comparison of cardiovascular outcomes between once-weekly semaglutide and dulaglutide in adults with type 2 diabetes and established atherosclerotic cardiovascular disease in the United States.. Diabetes, obesity & metabolism. https://doi.org/10.1111/dom.70440