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Noninferior is not better

In 13,299 people, tirzepatide matched an older, cheaper GLP-1 on heart attacks, strokes and cardiovascular death. It was not shown to beat it.

Neil Sanders5 min read
Cardiovascular death, heart attack or stroke0.921.00better, if cleared1.05margin0.831.01

Tirzepatide costs more than semaglutide almost everywhere here. Part of the reason is a general sense that it is the stronger drug. This trial tested a version of that belief against a different comparator, and the answer is narrower than the belief.

What the trial asked

It was an active-comparator, double-blind noninferiority trial in people with type 2 diabetes and atherosclerotic cardiovascular disease. [1] Participants were randomized 1:1 to weekly tirzepatide, titrated to as much as 15 mg, or to dulaglutide 1.5 mg — an older GLP-1 that the paper identifies as having already been shown to reduce cardiovascular events. 13,299 people were randomized, leaving 6,586 and 6,579 in the two analysis groups. Mean age was 64.1, mean HbA1c 8.4%, and mean diabetes duration 14.7 years.

The design matters more than usual here. A noninferiority trial asks whether the new drug is not meaningfully worse. The margin was set at 1.05 for the upper limit of the confidence interval. Superiority required that upper limit to fall below 1.00. Those are two different questions and the trial was built to answer the first. Which question a design can answer is settled before any data arrive — and so is which comparison gets reported, as the combination trial with an arm it never compared shows.

What it found

A primary endpoint event occurred in 801 patients on tirzepatide, 12.2%, and 862 on dulaglutide, 13.1%. The hazard ratio was 0.92 with a 95.3% confidence interval of 0.83 to 1.01. Noninferiority was met at P=0.003. Superiority was not, at P=0.09.

The upper bound is 1.01. It missed by a hundredth. That is worth saying plainly in both directions: the result is consistent with tirzepatide being modestly better, and the trial did not establish that it is.

Who paid, and who it was for

The trial was funded by Eli Lilly, which manufactures tirzepatide. That is ordinary for a cardiovascular outcomes trial and it is worth knowing, particularly for a result the sponsor would have preferred to be superior.

The population is also not the person reading this. These were people averaging nearly fifteen years of diabetes with established heart disease. Nothing here describes what either molecule does for cardiovascular risk in somebody buying for weight loss, and the cost of a cardiovascular result is a separate calculation entirely.

What it means for the price gap

Dulaglutide is not stocked by anybody on this roster, so this trial does not tell you which of two purchasable things to buy. What it does is put a limit on how much cardiovascular confidence the more expensive molecule has earned.

380 sellers here publish a price for both molecules by injection, read September 2026. Across those, tirzepatide runs a median of $60 more a month, with 341 charging more for it and 6 charging less. Whether that gap is worth paying is answered elsewhere on its own evidence, and this trial is one more input rather than the answer. You can see the current spread in the price check.

Frequently asked

Did tirzepatide beat the older drug?
No. It met noninferiority at P=0.003 and missed superiority at P=0.09. The hazard ratio was 0.92 with an upper confidence bound of 1.01, just above the 1.00 that superiority required.
Is that a bad result?
Not at all. Matching a drug already proven to reduce cardiovascular events is a meaningful finding. It is simply a different finding from being better than it.
Can I buy dulaglutide instead?
Not from anyone on this roster. No seller here stocks it, so this comparison bears on confidence rather than on a choice you can act on at checkout.
Does this apply to weight-loss buyers?
No. Participants averaged nearly fifteen years of type 2 diabetes and had established atherosclerotic cardiovascular disease.

Sources

  1. [1] Nicholls SJ, et al. (2025). Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes The New England Journal of Medicine. PMID 41406444

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