Retatrutide in obesity and overweight in adults: durability of effect — summary of findings
Outcome-by-outcome summary with effect, certainty and the reason for each downgrade.
Templated review frame. This review question was generated by crossing an indication with a compound for which contributing trials exist. Its prose frame is templated and is shared with other questions of the same shape. Its included studies, its summary of findings and its certainty rating are computed from the underlying records and are not templated. The Institute publishes these questions because the alternative is to leave a question the document set can answer unanswered, and it labels them because the alternative is to present a templated frame as an authored one.
§4Summary of findings
§4.1Summary of findings
Table 7. Summary of findings for Retatrutide in obesity and overweight in adults: durability of effect.
| Outcome | Participants (studies) | Effect as reported | Certainty | Reason for downgrade |
|---|---|---|---|---|
| Percentage change in body weight from baselineThe outcome the Institute designates as anchor for this indication. | 338 (5) | Mean change −24.2 % at 12 mg versus −2.1 % with placebo | Moderate | indirectness |
| Discontinuation for adverse eventsReported as a summary-of-findings row rather than in a tolerability annex, following a public submission. | 253 (4) | Reported per contributing trial; see the included-studies table | Moderate | indirectness |
| Serious adverse eventsEvent counts are low; the estimate is imprecise by construction. | 267 (4) | Reported per contributing trial; see the included-studies table | Low | inconsistency, indirectness |
| Any adverse eventAscertained by spontaneous report in the contributing trials. | 260 (3) | Reported per contributing trial; see the included-studies table | Low | risk of bias, imprecision |
| Proportion achieving ≥5 %, ≥10 %, ≥15 % and ≥20 % weight reductionA secondary outcome for this indication. Its hierarchical position within each contributing trial is recorded on that trial's abstract where the Institute holds it. | 188 (4) | Reported as a secondary outcome in a subset of contributing trials | Low | risk of bias, publication bias |
| Change in waist circumferenceA secondary outcome for this indication. Its hierarchical position within each contributing trial is recorded on that trial's abstract where the Institute holds it. | 269 (4) | Reported as a secondary outcome in a subset of contributing trials | Low | indirectness, publication bias |
| Certainty ratings describe confidence in the effect estimate for the stated outcome. They are not recommendations and do not transfer between outcomes. | ||||
§4.2Forest plot
§4.3Certainty assessment for the anchor outcome
Table 8. Reasoning recorded against each certainty domain for the anchor outcome.
| Domain | Rating | Reasoning |
|---|---|---|
| Risk of bias | No concern | No serious concern identified in this domain. |
| Inconsistency | No concern | No serious concern identified in this domain. |
| Indirectness | Serious | The outcome is a surrogate whose relationship to the clinical outcome is unvalidated for this indication. |
| Imprecision | No concern | No serious concern identified in this domain. |
| Publication bias | No concern | No serious concern identified in this domain. |
| Overall: Moderate certainty. The true effect is likely to be close to the estimate, but there is a possibility that it is substantially different. Further research is likely to have an important impact on confidence in the estimate. | ||
References cited on this page
References are numbered in order of first citation in this document. Each superscript in the text links to its entry below.
- Jastreboff AM, Kaplan LM, Frías JP, Wu Q, Du Y, Gurbuz S, Coskun T, Haupt A, Milicevic Z, Hartman ML. Triple-hormone-receptor agonist retatrutide for obesity — a phase 2 trial. New England Journal of Medicine 2023;389(6):514–526. doi:10.1056/NEJMoa2301972 · PMID 37366315
- Rosenstock J, Frias J, Jastreboff AM, Du Y, Lou J, Gurbuz S, Thomas MK, Hartman ML, Haupt A, Milicevic Z, Coskun T. Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo- and active-controlled, parallel-group, phase 2 trial. The Lancet 2023;402(10401):529–544. doi:10.1016/S0140-6736(23)01053-X · PMID 37385280
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