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Compound Evidence InstituteEvidence synthesis · established 2023Graded assessments of compounds, trials, methods and supply
Document set current to 30 July 2026
Evidence synthesis · §4

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.

Document identifier
CEI-ES-125/4
Series
Evidence synthesis
Version
2.1
Published
16 Mar 2025
Last reviewed
16 Nov 2025
Next review
16 May 2027
Identifier
10.71829/cei.syn.125
Certainty
Moderate
Cycle
2025 Q1
Review type
Intervention review
Search executed
23 Dec 2024

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.

OutcomeParticipants (studies)Effect as reportedCertaintyReason 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 placeboModerateindirectness
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 tableModerateindirectness
Serious adverse eventsEvent counts are low; the estimate is imprecise by construction.267 (4)Reported per contributing trial; see the included-studies tableLowinconsistency, indirectness
Any adverse eventAscertained by spontaneous report in the contributing trials.260 (3)Reported per contributing trial; see the included-studies tableLowrisk 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 trialsLowrisk 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 trialsLowindirectness, 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

Contributing estimatesPoint estimates with confidence intervals for each contributing study, plotted against the line of no effect.0.50.751Ratio measure, log scale (1 = no effect)Contributing studyEstimate (95 % CI)RETA-PH2-OBESITY2023 · n=3380.91 (0.66 to 1.16)TRIUMPH-1 · n=not held0.46 (0.37 to 0.54)TRIUMPH-2 · n=not held0.53 (0.40 to 0.67)TRIUMPH-3 · n=not held0.69 (0.54 to 0.84)TRIUMPH-4 · n=not held0.71 (0.53 to 0.89)Pooled estimate0.63 (0.55 to 0.71)
Study estimatePooled estimate
Figure 1. Illustrative. Contributing estimates plotted against the line of no effect. The point estimates and intervals are the Institute's standardised representation of the contributing evidence on a common ratio scale, generated deterministically from the record identifiers; they are not the published estimates, which appear in their own units in the included-studies table and on each trial abstract. The figure is published to convey the dispersion of the evidence base, not to supply a number.

§4.3Certainty assessment for the anchor outcome

Certainty assessment by domainDowngrading decision recorded for each certainty domain.Certainty domainNo concernSeriousVery seriousEffect on ratingRisk of biasno downgradeInconsistencyno downgradeIndirectnessdowngrade one levelImprecisionno downgradePublication biasno downgradeTotal downgrading: 1 levelModerate certainty
Figure 2. Domain-by-domain certainty assessment for the anchor outcome of this review.

Table 8. Reasoning recorded against each certainty domain for the anchor outcome.

DomainRatingReasoning
Risk of biasNo concernNo serious concern identified in this domain.
InconsistencyNo concernNo serious concern identified in this domain.
IndirectnessSeriousThe outcome is a surrogate whose relationship to the clinical outcome is unvalidated for this indication.
ImprecisionNo concernNo serious concern identified in this domain.
Publication biasNo concernNo 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.

  1. 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
  2. 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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