Retatrutide phase 2 (obesity) — trial digest
Retatrutide phase 2 (obesity) (N Engl J Med 2023): What is the dose-response for retatrutide on body weight?
Citation and design
| Field | Value |
|---|---|
| Trial | Retatrutide phase 2 (obesity) |
| Intervention | Retatrutide, several dose arms |
| Publication | N Engl J Med, 2023 (first author Jastreboff) |
| Design | Double-blind, placebo-controlled, dose-finding, 48 weeks |
| Population | Adults with obesity |
This digest summarises the trial and the criticisms our journal club considered material. It is not a substitute for the paper, and where the two differ the paper is right.
The question it set out to answer
What is the dose-response for retatrutide on body weight?
Stating the question before the result is a house convention. A great many arguments about this trial are actually arguments about what it was for.
What it found
A dose-finding trial, not a pivotal trial, and it should always be described that way.
Weight reduction at the higher doses was of a magnitude that generated substantial interest, with no clear plateau by week 48.
Dose-dependent heart-rate increase was observed and is one of the things phase 3 exists to characterise.
Criticisms the journal club considered material
- Phase 2 sample sizes are not adequate for safety characterisation of a novel triple agonist.
- The absence of a plateau means the curve had not finished, so the reported figures are not an endpoint.
- No phase 3 results exist. TRIUMPH is ongoing and nothing should be attributed to it.
These are criticisms of the design and of how the result is used, not of the investigators. Sessions that lose that distinction get moderated.
How it is misused
The two recurring misuses of this trial in general discussion are quoting the relative effect without the absolute one, and extending the result to a population the trial did not enrol. Both are easy to correct and both keep happening.
Where a number appears in secondary coverage without an estimand attached, assume it is whichever version is larger and check the paper.
Maintenance
Digests are reviewed when new analyses of the same trial are published, and at the review date shown above regardless. If a secondary publication changes the picture, raise it in journal club rather than editing the digest directly, so the change is discussed before it lands.
Revision history
| 2025-07-17 | hana.sato | Reverted an unsourced change and asked the editor to re-apply it with a citation. |
| 2025-06-08 | j.delacroix | Added cross-references to the two topics that most often ask this question. |
| 2025-05-15 | sourced_claims | Annual review: checked every figure against its source. Two rounded values tightened. |
| 2025-01-13 | ms_holloway | Restructured into shorter sections so the outline navigation is usable. |
| 2024-10-24 | unit_conversion | Initial promotion from the source topic. Structure taken from the marked solution. |
Every edit to a maintained document records its author and a note explaining the change. An edit without a note may be reverted by any wiki editor under R9, and the revert is logged. Disagreements about content belong on the source topic rather than in the revision history (R10).
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