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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

Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists — summary of findings

Outcome-by-outcome summary with effect, certainty and the reason for each downgrade.

Document identifier
CEI-ES-003/4
Series
Evidence synthesis
Version
3.0
Published
24 Nov 2024
Last reviewed
24 Oct 2025
Next review
24 Apr 2027
Identifier
10.71829/cei.syn.3
Certainty
High
Cycle
2024 Q4
Review type
Intervention review
Search executed
07 Sep 2024

§4Summary of findings

§4.1Summary of findings

Table 7. Summary of findings for Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists.

OutcomeParticipants (studies)Effect as reportedCertaintyReason for downgrade
Three-point major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke)The outcome the Institute designates as anchor for this indication.87,425 (11)High certainty evidence indicates that the class as a whole reduces major adverse cardiovascular events relative to placebo in the enrolled…Highno downgrade
Discontinuation for adverse eventsReported as a summary-of-findings row rather than in a tolerability annex, following a public submission.73,489 (9)Reported per contributing trial; see the included-studies tableHighno downgrade
Serious adverse eventsEvent counts are low; the estimate is imprecise by construction.77,408 (9)Reported per contributing trial; see the included-studies tableModerateindirectness
Any adverse eventAscertained by spontaneous report in the contributing trials.81,284 (10)Reported per contributing trial; see the included-studies tableModerateimprecision
Cardiovascular deathA secondary outcome for this indication. Its hierarchical position within each contributing trial is recorded on that trial's abstract where the Institute holds it.70,911 (10)Reported as a secondary outcome in a subset of contributing trialsModeraterisk of bias
All-cause deathA secondary outcome for this indication. Its hierarchical position within each contributing trial is recorded on that trial's abstract where the Institute holds it.45,558 (10)Reported as a secondary outcome in a subset of contributing trialsModerateimprecision
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)SOUL2025 · n=9,6500.79 (0.69 to 0.89)SELECT2023 · n=17,6040.81 (0.61 to 1.00)AMPLITUDE-O2021 · n=4,0760.62 (0.49 to 0.76)PIONEER-62019 · n=3,1830.60 (0.52 to 0.67)REWIND2019 · n=9,9010.92 (0.68 to 1.16)HARMONY-OUTCOMES2018 · n=9,4630.60 (0.53 to 0.67)EXSCEL2017 · n=14,7520.82 (0.73 to 0.90)EMBRACE-STEMI2016 · n=910.96 (0.73 to 1.20)LEADER2016 · n=9,3400.72 (0.55 to 0.90)SUSTAIN-62016 · n=3,2970.88 (0.77 to 0.99)Pooled estimate0.79 (0.69 to 0.89)
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 downgradeIndirectnessno downgradeImprecisionno downgradePublication biasno downgradeTotal downgrading: 0 levelsHigh 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.
IndirectnessNo concernNo serious concern identified in this domain.
ImprecisionNo concernNo serious concern identified in this domain.
Publication biasNo concernNo serious concern identified in this domain.
Overall: High certainty. The Institute is confident that the true effect lies close to the estimate. Further research is very unlikely to change 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. 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
  2. Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jódar E, Leiter LA, Lingvay I, Rosenstock J, Seufert J, Warren ML, Woo V, Hansen O, Holst AG, Pettersson J, Vilsbøll T. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. New England Journal of Medicine 2016;375(19):1834–1844. doi:10.1056/NEJMoa1607141 · PMID 27633186

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.

Compound Evidence Institute · CEI-ES-003/4 · https://compoundevidence.com/syntheses/incretin-cardiovascular-outcomes/summary-of-findings/ · retrieved 30 July 2026
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