Dispatch 001: Five Retatrutide Phase 3 Trials Have Finished And None Has Posted Results

What this dispatch is

Most newsletters in this field report press releases. A press release is a company describing its own trial before anyone can inspect it, which is the weakest form of evidence that still counts as news. This one works from the registries instead, which means it is sometimes less exciting and always checkable. The first issue turns out to be mostly about absence, which is itself the story.

Five retatrutide phase 3 trials have finished and none has posted results

This is the most-asked question about retatrutide and the honest answer is not a number. It is that the numbers are sitting somewhere unpublished. Below is every phase 3 retatrutide trial that has passed primary completion, read live from ClinicalTrials.gov for this issue.

A gap between finishing a trial and posting its results is normal and partly lawful: US rules generally allow twelve months from primary completion, and results often appear at a conference or in a journal before they reach the registry. So this is not an accusation. It is a statement about what you can and cannot know today, which matters if you are making a decision about retatrutide on the strength of what you have read somewhere. What is publicly verifiable right now is phase 2 data. Anything presented as a phase 3 retatrutide result should be traceable to a specific conference presentation or paper, and if it is not, treat it as a rumour.

A CagriSema versus tirzepatide phase 3 completed, at a dose worth noticing

Read the comparator dose before you read the eventual headline. Tirzepatide is approved at 5, 10 and 15 mg maintenance doses, and its largest effects come at 10 and 15. This trial fixed it at 5 mg, the lowest of the three. There may be a defensible reason, since 5 mg is a legitimate maintenance dose and matching it to a low CagriSema dose has a logic to it. There is also an obvious commercial one, and Novo Nordisk both sponsors this trial and sells the drug being compared against its own.

The reason to flag it now, before results exist, is that a dose choice is invisible once a result becomes a headline. This site already reports one CagriSema head to head that went the other way: in REDEFINE 4, 809 participants over 84 weeks, CagriSema lost to tirzepatide 15 mg on weight, 23.0 percent against 25.5 percent, and missed non-inferiority. Same two drugs, different doses, opposite framing available. See CagriSema, tirzepatide and the head to head comparison.

378 randomised trials ranked what prevents diabetes, and a supplement placed

Two things in this paper are worth more than the ranking itself. The first is how close metformin plus lifestyle came to single-agent GLP-1: 0.27 against 0.26, which for a generic drug plus a behaviour programme is a striking result and one that almost never makes a headline. See metformin.

The second is the HbA1c list. Only four interventions achieved more than a 0.3 percent HbA1c reduction at one year, and curcumin was one of them, at minus 0.49 percent, ahead of single GLP-1 agonism at minus 0.41. That is a surprising placement for a plant extract and it needs the caveat this site puts on every curcumin result: the trials use specific enhanced-absorption formulations rather than turmeric, and a network meta-analysis inherits the quality of what it pools. Read it as a reason to take the compound seriously and not as a reason to expect a drug-sized effect. Profile: curcumin, and the supplements pillar explains why a marker and a retest matter more than a ranking.

Also logged this fortnight

• A network meta-analysis compared tirzepatide against dulaglutide in type 2 diabetes with and without established atherosclerotic cardiovascular disease. Network comparisons are indirect: they estimate a head to head that nobody ran, which is useful and is not the same as a trial.
• A systematic review and meta-analysis examined incretin receptor agonists in people who have had metabolic bariatric surgery, a population that is growing quickly and has almost no dedicated randomised evidence.
• SYNERGY-Outcomes (NCT07165028) began recruiting: a 4,500-person phase 3 master protocol testing tirzepatide and retatrutide against placebo in metabolic dysfunction-associated steatotic liver disease, with a hard composite liver outcome as the primary endpoint rather than a biomarker. Primary completion is August 2030.
• A phase 2 trial of tirzepatide in 134 people with overweight or obesity and chronic kidney disease (NCT05536804) completed. Small, and kidney endpoints in this drug class are where the interesting long-term questions are.

How to read a dispatch

1. 01Check whether the item is a result or a registration. A completed trial with no posted results tells you data exists, not what it says.
2. 02Check the comparator and its dose. A head to head against a low dose of the rival drug is a different claim than a head to head at its best dose.
3. 03Check who paid. It does not make a result wrong, and it tells you which way the design decisions were likely to lean.
4. 04Check whether the endpoint is something that happens to a person or a number in a tube. Both matter. They are not interchangeable.
5. 05Follow the link to the profile. A single new paper rarely changes a picture, and the profile is where the whole picture lives.