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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 · §3

Percentage weight change as a surrogate outcome — included and excluded studies

The included-studies table with extracted data, the exclusions with reasons, and the risk-of-bias judgements.

Document identifier
CEI-ES-019/3
Series
Evidence synthesis
Version
2.3
Published
26 Jan 2026
Last reviewed
26 Jan 2026
Next review
26 Jul 2027
Identifier
10.71829/cei.syn.19
Certainty
Low
Cycle
2026 Q1
Review type
Methodological review
Search executed
17 Nov 2025

§3Included and excluded studies

Every study contributing to this review is listed below with the data extracted from it. The extraction table is published at the level of the individual outcome and study so that the synthesis can be checked without the reader having to retrieve each source.

§3.1Included studies

Table 4. Included studies with the characteristics extracted from each.

StudyDesignRandomisedDurationAnchor outcome as reportedYear
ATTAIN-1OrforglipronRandomised, double-blind, placebo-controlled72 weeksThe Institute holds a headline result indicating a weight effect intermediate between the injectable single agonists and placebo, and awaits the full…2025
ATTAIN-2OrforglipronRandomised, double-blind, placebo-controlled72 weeksno result held2025
ECNO-PH3-CN-OBESITYEcnoglutideRandomised, double-blind, placebo-controlled66448 weeksMean change −13.2 % at 2.4 mg versus −0.5 % with placebo2025
GLORY-1MazdutideRandomised, double-blind, placebo-controlled61048 weeksMean change −14.0 % at 6 mg versus +0.3 % with placebo2025
REDEFINE-1CagriSema (cagrilintide with semaglutide)Randomised, double-blind, placebo-controlled3,41768 weeksMean change −22.7 % versus −2.3 % with placebo2025
REDEFINE-2CagriSema (cagrilintide with semaglutide)Randomised, double-blind, placebo-controlled1,20668 weeksMean change −15.7 % versus −3.1 % with placebo2025
SOULSemaglutide, oralEvent-driven cardiovascular outcome trial9,650Median 47.5 monthsHazard ratio 0.86 (95 % CI 0.77 to 0.96)2025
SURMOUNT-5TirzepatideRandomised, open-label, active-controlled75172 weeksMean change −20.2 % with tirzepatide versus −13.7 % with semaglutide2025
SURMOUNT-KOATirzepatideRandomised, double-blind, placebo-controlled68 weeksImprovement relative to placebo. The Institute records that pain improvement in a weight-loss trial cannot be attributed to a direct joint effect2025
SURPASS-CVOTTirzepatideEvent-driven cardiovascular outcome trial13,299Median 4.5 yearsNon-inferior to dulaglutide on the primary composite. The Institute records that an active-controlled non-inferiority design cannot establish superiority over…2025
MARITIDE-PH2-OBESITYMaridebart cafraglutideRandomised, double-blind, placebo-controlled59252 weeksMean change of approximately −20 % at the highest dose without a weight plateau at 52 weeks2024
PETRE-PH1BPetrelintidePhase 1 ascending dose16 weeksWeight reduction of approximately 8.6 % at 16 weeks in a phase 1b setting2024
REIMAGINE-1AmycretinPhase 1 ascending dose125Up to 36 weeksExploratory weight reduction of approximately 13 % at 12 weeks with the subcutaneous presentation. The Institute treats an exploratory endpoint in a phase 1…2024
SUMMITTirzepatideRandomised, double-blind, placebo-controlled731Median 104 weeksHazard ratio 0.62 (95 % CI 0.41 to 0.95) for the composite; clinical summary score difference 6.9 points (95 % CI 3.3 to 10.6)2024
SURMOUNT-4TirzepatideRandomised withdrawal67052 weeks after a 36-week open-label lead-inContinued treatment −5.5 % versus +14.0 % after switching to placebo2024
SURMOUNT-OSA-1TirzepatideRandomised, double-blind, placebo-controlled52 weeksSubstantial reduction in the apnoea–hypopnoea index relative to placebo; the Institute reproduces the pooled programme estimate rather than a per-trial figure2024
SURMOUNT-OSA-2TirzepatideRandomised, double-blind, placebo-controlled52 weeksDirectionally consistent with the companion trial2024
SURVO-PH2-OBESITYSurvodutideRandomised, double-blind, placebo-controlled38746 weeksMean change −18.7 % at the highest dose versus −1.8 % with placebo2024
CAGRI-SEMA-PH2-T2DCagriSema (cagrilintide with semaglutide)Randomised, double-blind, active-controlled9232 weeksWeight change of approximately −15.6 % in the combination arm; the small sample is the reason the Institute treats the phase 2 estimate as hypothesis-generating2023
DANU-PH2B-OBESITYDanuglipronRandomised, double-blind, placebo-controlled60532 weeksDose-dependent weight reduction accompanied by discontinuation rates above 50 % in some arms; development in obesity was subsequently discontinued2023
MAZ-PH2-OBESITYMazdutideRandomised, double-blind, placebo-controlled24824 weeksMean change up to −15.4 % at the highest dose in a Chinese population2023
OASIS-1Semaglutide, oralRandomised, double-blind, placebo-controlled66768 weeksMean change −15.1 % versus −2.4 % with placebo2023
ORFO-PH2-OBESITYOrforglipronRandomised, double-blind, placebo-controlled27236 weeksMean change up to −14.7 % versus −2.3 % with placebo2023
RETA-PH2-OBESITYRetatrutideRandomised, double-blind, placebo-controlled33848 weeksMean change −24.2 % at 12 mg versus −2.1 % with placebo2023
24 included studies. Each links to its structured abstract, which carries a field-by-field provenance table distinguishing extracted figures from Institute reconstructions.

Contributing participants across studies reporting a randomised total: 34,324. Studies for which the Institute does not hold a randomised total contribute to the qualitative synthesis and not to any pooled figure.

§3.2Excluded at full text, with reasons

Table 5. Reports excluded at full text, by reason. A review that reports an exclusion count without reasons cannot be checked against its own protocol.

Reason for exclusionReports
Not a randomised comparison11
Population outside the review question10
Intervention outside the review question17
Comparator not eligible20
No eligible outcome reported15
Duplicate report of an included study13
Conference abstract without extractable data11
Retracted or subject to an expression of concern8
72 reports excluded at full text in total.

§3.3Risk of bias across included studies

Table 6. Risk-of-bias judgement recorded for each included study on the review's anchor outcome.

StudyRisk of biasInconsistencyIndirectnessImprecisionPublication bias
ATTAIN-1LowSomeLowLowLow
ATTAIN-2SomeLowLowSomeLow
ECNO-PH3-CN-OBESITYHighLowLowLowLow
GLORY-1LowLowLowSomeLow
REDEFINE-1LowLowLowSomeLow
REDEFINE-2LowSomeLowLowLow
SOULLowLowSomeLowLow
SURMOUNT-5LowLowLowLowLow
SURMOUNT-KOASomeLowLowSomeLow
SURPASS-CVOTLowLowLowLowSome
MARITIDE-PH2-OBESITYSomeLowLowSomeLow
PETRE-PH1BLowHighLowLowLow
REIMAGINE-1LowLowLowLowHigh
SUMMITLowLowSomeLowLow
Judgements are the Institute's own and are recorded per outcome. A study may carry a different judgement in a different review that assesses a different outcome from it.

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. Lincoff AM, Brown-Frandsen K, Colhoun HM, Deanfield J, Emerson SS, Esbjerg S, Hardt-Lindberg S, Hovingh GK, Kahn SE, Kushner RF, Lingvay I, Oral TK, Michelsen MM, Plutzky J, Tornøe CW, Ryan DH. Semaglutide and cardiovascular outcomes in obesity without diabetes. New England Journal of Medicine 2023;389(24):2221–2232. doi:10.1056/NEJMoa2307563 · PMID 37952131

Identifiers are reproduced only where the Institute holds them. Where a digital object identifier or PubMed identifier is not shown, the Institute has recorded the journal and year and has not constructed an identifier.

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