Independent · non-commercial · publishes on a quarterly cycle|Current cycle 2026 Q3
Compound Evidence InstituteEvidence synthesis · established 2023Graded assessments of compounds, trials, methods and supply
Document set current to 30 July 2026
Evidence synthesis · §3

Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists — 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-003/3
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

§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
SOULSemaglutide, oralEvent-driven cardiovascular outcome trial9,650Median 47.5 monthsHazard ratio 0.86 (95 % CI 0.77 to 0.96)2025
SELECTSemaglutideEvent-driven cardiovascular outcome trial17,604Mean 39.8 monthsHazard ratio 0.80 (95 % CI 0.72 to 0.90); 6.5 % versus 8.0 %2023
AMPLITUDE-OExenatideEvent-driven cardiovascular outcome trial4,076Median 1.8 yearsHazard ratio 0.73 (95 % CI 0.58 to 0.92), with a composite kidney outcome also reduced2021
PIONEER-6Semaglutide, oralEvent-driven cardiovascular outcome trial3,183Median 15.9 monthsHazard ratio 0.79 (95 % CI 0.57 to 1.11); the trial was designed and powered to exclude harm, not to establish benefit, and the Institute reports it as such2019
REWINDDulaglutideEvent-driven cardiovascular outcome trial9,901Median 5.4 yearsHazard ratio 0.88 (95 % CI 0.79 to 0.99)2019
HARMONY-OUTCOMESDulaglutideEvent-driven cardiovascular outcome trial9,463Median 1.6 yearsHazard ratio 0.78 (95 % CI 0.68 to 0.90)2018
EXSCELExenatideEvent-driven cardiovascular outcome trial14,752Median 3.2 yearsHazard ratio 0.91 (95 % CI 0.83 to 1.00); the trial did not meet its superiority threshold2017
EMBRACE-STEMIExenatideRandomised, double-blind, placebo-controlled916 monthsNo significant reduction in infarct size2016
LEADERLiraglutideEvent-driven cardiovascular outcome trial9,340Median 3.8 yearsHazard ratio 0.87 (95 % CI 0.78 to 0.97)2016
SUSTAIN-6SemaglutideEvent-driven cardiovascular outcome trial3,297104 weeksHazard ratio 0.74 (95 % CI 0.58 to 0.95); designed to exclude harm rather than to establish benefit2016
ELIXALixisenatideEvent-driven cardiovascular outcome trial6,068Median 25 monthsHazard ratio 1.02 (95 % CI 0.89 to 1.17); neutral2015
11 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: 87,425. 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 comparison5
Population outside the review question12
Intervention outside the review question7
Comparator not eligible3
No eligible outcome reported9
Duplicate report of an included study8
Conference abstract without extractable data11
Retracted or subject to an expression of concern11
50 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
SOULLowSomeLowLowLow
SELECTLowLowLowLowLow
AMPLITUDE-OLowLowSomeLowLow
PIONEER-6LowLowLowLowLow
REWINDLowLowLowLowLow
HARMONY-OUTCOMESSomeLowLowLowLow
EXSCELLowLowLowLowLow
EMBRACE-STEMISomeLowLowLowLow
LEADERLowLowLowLowLow
SUSTAIN-6LowLowLowLowLow
ELIXALowLowLowLowLow
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.

Nothing published by the Institute is medical advice, a diagnosis, a prescription, a treatment recommendation or a purchasing recommendation. Compounds supplied for research use are not approved for human or veterinary use in any jurisdiction, and a favourable analytical assessment of a supplier is not a statement that any product is safe or effective. The Institute publishes certainty ratings and never recommendations. No telephone number, messaging handle or ordering channel appears anywhere on this site.