CATEGORY: METABOLIC & BLOOD SUGAR
The investigators were betting on a win, and they did not get one. Tirzepatide was tested head to head against dulaglutide in 13,165 adults with type 2 diabetes and established heart disease, and over a median of four years it did not beat the older drug at preventing heart attacks, strokes and cardiovascular deaths. It matched it: 12.2% against 13.1%.1 On blood sugar and body weight, where the two medicines were expected to differ, tirzepatide finished well ahead. Deaths from any cause were also less frequent with it, 8.6% against 10.2%.
One Key or Two
Both drugs come from the family of injectable diabetes medicines built on gut hormones, and they are not the same. Dulaglutide works like a key that fits one lock, switching on the receptor for GLP-1, a hormone that boosts insulin release and dampens appetite. Tirzepatide carries two keys. It turns on the GLP-1 receptor and a second one called GIP, which is why it moves weight and blood sugar further. Whether the stronger drug guarded the heart as well as the older one was unknown. Dulaglutide had already earned its cardiovascular credentials in a large placebo-controlled trial.
Not Placebo, but a Drug That Already Works
The trial, called SURPASS-CVOT, handed out weekly injections of one drug or the other by randomization, with both sides blinded, then counted heart attacks, strokes and deaths from cardiovascular causes. The average participant was 64 years old, with 15 years of diabetes behind them. All had established cardiovascular disease. Testing a new drug against a proven active treatment rather than a placebo sets the bar deliberately high, because the comparison drug is already preventing events.
Level on Hearts, Ahead on Everything Metabolic
Major cardiovascular events were 8% less frequent with tirzepatide, but that difference fell short of statistical significance. So the formal verdict is no worse, not better. Where the two drugs were expected to part, they did. HbA1c, the three-month average blood sugar, fell 1.66 percentage points on tirzepatide against 0.88 on dulaglutide, and body weight fell 11.6% against 4.8%. Stomach side effects such as nausea were more common with tirzepatide, 42.5% against 35.9%.
Fewer Deaths, and How Much Weight That Carries
Death from any cause ran 16% lower with tirzepatide, 8.6% against 10.2%. That was a secondary result. The trial was not primarily built to test it, so it deserves the lighter weight secondary findings carry. In a trial this large and this long it is still a signal worth watching, and it arrived alongside better kidney-function trends among higher-risk participants. Taken together, the two widely used injections sit shoulder to shoulder on heart protection, with the newer one adding bigger metabolic gains and more stomach upset.
Key Takeaways
- Over a median of four years in 13,165 adults with type 2 diabetes and heart disease, tirzepatide matched dulaglutide on heart attack, stroke and cardiovascular death, 12.2% against 13.1%. Superiority was tested and not established.
- HbA1c and body weight fell considerably further on tirzepatide, and gastrointestinal side effects were more common.
- Death from any cause was less frequent with tirzepatide, 8.6% against 10.2%, a secondary finding that carries less certainty than the trial’s main result.
References
- Nicholls SJ, et al. Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes. The New England Journal of Medicine. 2025;393:2409–2420. link