SURPASS-4 — trial digest
SURPASS-4 (Lancet 2021): How does tirzepatide compare with basal insulin in a higher-risk diabetes population?
Citation and design
| Field | Value |
|---|---|
| Trial | SURPASS-4 |
| Intervention | Tirzepatide versus insulin glargine |
| Publication | Lancet, 2021 (first author Del Prato) |
| Design | Open-label, active-controlled, up to 104 weeks |
| Population | Adults with type 2 diabetes at increased cardiovascular risk |
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
How does tirzepatide compare with basal insulin in a higher-risk diabetes population?
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 longest exposure in the SURPASS programme and the one with a cardiovascular-risk population.
Greater glycaemic reduction with weight loss rather than the weight gain expected with insulin.
Cardiovascular events were captured and adjudicated, though the trial was not a dedicated outcome trial.
Criticisms the journal club considered material
- Insulin glargine titration in a trial is not necessarily equivalent to titration in practice, in either direction.
- Not designed or powered as a cardiovascular outcome trial; the cardiovascular data is reassurance rather than evidence of benefit.
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
| 2025-10-18 | KLindqvist | Restructured into shorter sections so the outline navigation is usable. |
| 2025-07-17 | batchlog | Added the table of acceptance criteria requested in doc review. |
| 2025-06-10 | KAndersson | Plain-language pass on the opening section after feedback from a newcomer. |
| 2025-01-25 | chromatogram | Added the limitations paragraph. The page previously implied more certainty than the sources carry. |
| 2024-10-09 | logbook_erin | 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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