SURMOUNT-4 — trial digest
SURMOUNT-4 (JAMA 2024): What happens when tirzepatide is withdrawn after maintenance is reached?
Citation and design
| Field | Value |
|---|---|
| Trial | SURMOUNT-4 |
| Intervention | Tirzepatide, continuation versus withdrawal |
| Publication | JAMA, 2024 (first author Aronne) |
| Design | Randomised withdrawal after 36 weeks of open-label lead-in, then 52 weeks |
| Population | Adults with obesity or overweight without diabetes |
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What happens when tirzepatide is withdrawn after maintenance is reached?
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
The tirzepatide counterpart to STEP 4, and it reproduces the same qualitative finding: continuation maintains and extends, withdrawal is followed by regain.
The reproduction across two compounds and two sponsors makes the finding considerably more robust than either trial alone.
Criticisms the journal club considered material
- The open-label lead-in selects responders and tolerators, as in STEP 4.
- Again, no information about a lower maintenance dose, which is the question that would be most useful.
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
| 2026-06-29 | crossref_check | Citation sweep: two references did not support the sentences attached to them and have been replaced. |
| 2026-05-24 | KLindqvist | Removed a paragraph that duplicated a linked page, and linked it instead. |
| 2026-01-09 | a.salcedo | Plain-language pass on the opening section after feedback from a newcomer. |
| 2025-10-08 | customs_ledger | Added the table of acceptance criteria requested in doc review. |
| 2025-08-04 | impurity_table | Added cross-references to the two topics that most often ask this question. |
| 2025-03-07 | dexa_twice_yearly | 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).
Related documents
- STEP 1 — trial digestSTEP 1 (N Engl J Med 2021): Does semaglutide 2.4 mg weekly reduce body weight in adults with obesity and no diabetes?
- STEP 2 — trial digestSTEP 2 (Lancet 2021): What weight reduction does semaglutide 2.4 mg achieve in people who also have type 2 diabetes?
- STEP 3 — trial digestSTEP 3 (JAMA 2021): What does semaglutide add on top of intensive behavioural therapy?
- STEP 4 — trial digestSTEP 4 (JAMA 2021): What happens if you stop after reaching the maintenance dose?
- STEP 8 — trial digestSTEP 8 (JAMA 2022): How does weekly semaglutide compare directly with daily liraglutide?