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Tirzepatide against dulaglutide: one trial is 92% of the network

A four-trial network meta-analysis of 14,348 participants. One study supplies 13,165 of them, and every published difference is measured against tirzepatide 5 mg.

Glenn Torres7 min read
A four-trial network, by participantNicholls 2025 — 13,165the other three: 1,183 between them91.8% of the participants come from one study.Every difference below is measured against tirzepatide 5 mgTZP 15 mg −2.68 kg · TZP 1 mg +4.39 kg · DULA 0.75 mg +3.10 kg

Four trials went into this. One of them is almost all of it.

Where the weight sits

The headline number is 14,348 participants. Of those, 13,165 came from a single 2025 trial. [1] The remaining three studies contributed 1,183 people between them.

So this is one large trial with three small ones attached. That is not a criticism of the method. It is a description of what the method had to work with, and it changes how much a seven-node network can tell you — the same reason one famous trial and a whole evidence base give different answers.

The results, with their reference arm

Every difference is published against tirzepatide 5 mg. At week 16, tirzepatide 15 mg took off 2.68 kg more, 95% CI −4.98 to −0.38. Tirzepatide 1 mg took off 4.39 kg less and dulaglutide 0.75 mg 3.10 kg less.

On HbA1c at week 24, tirzepatide 15 mg gave 0.40 points more reduction and 10 mg gave 0.23 more. Dulaglutide 1.5 mg came in at +0.67%, which reads as a worse reduction, not a better one. Drop the reference arm from any of those sentences and they stop meaning anything.

What did not differ

All-cause mortality and major cardiovascular events showed no significant difference between any treatment in the network.

With 446 fewer events than you would want, that null is uninformative rather than reassuring. The authors say as much when they flag limited event counts, and a pooled figure built this way carries the same problem as two poolings of the same trials disagreeing.

The split the title promises

The paper is titled for patients with and without established atherosclerotic cardiovascular disease. The abstract reports no such split.

The full text may carry it and we have not read the full text. What can be said is that anyone quoting this as evidence about the ASCVD subgroup is quoting something the abstract does not contain.

What to take

More tirzepatide does more, and costs more nausea. That is the finding, and it was not much in doubt.

The dose-by-dose ranking is the new part, and it is the part resting on indirect comparisons and pre-maintenance doses — so read it as an ordering to test rather than one to buy on, the way a pooled average almost nobody experienced is a summary rather than a forecast.

Frequently asked

Is tirzepatide better than dulaglutide?
At higher doses it produced larger weight and HbA1c reductions in this network. Every comparison is against tirzepatide 5 mg rather than head to head, and several are indirect.
Why does one trial matter so much here?
It supplies 13,165 of the 14,348 participants, or 91.8%. The other three trials contribute 1,183 people between them, so the network is one large study with three small ones attached.
Were there safety differences?
No significant difference in all-cause mortality or major cardiovascular events. Gastrointestinal side effects rose with tirzepatide dose, particularly nausea at 15 mg.
What does the paper say about established heart disease?
Its title names that stratification, but the abstract reports no such split. Anyone citing it as evidence about that subgroup is citing something the abstract does not contain.

Sources

  1. [1] Hageen AW, et al. (2026). Efficacy and Safety of Tirzepatide Versus Dulaglutide in Type 2 Diabetes With or Without Established Atherosclerotic Cardiovascular Disease: A Network Meta-Analysis of Randomized Clinical Trials Endocrinology, Diabetes & Metabolism. PMID 42706739

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