Evidence map›Paper›PMID 40849664›Full record

Trial reportCardiovascular diabetology2025

Impact of changes in conventional risk factors induced by once-weekly GLP-1 receptor agonist exenatide on cardiovascular outcomes: an EXSCEL post hoc analysis.

Ruth L Coleman, Amanda I Adler, Robert J Mentz, Marat Fudim, Naveed Sattar, Rury R Holman

Abstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Cardiovascular diabetology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Trial
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Ruth L ColemanDiabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LJ, UK. ruth.coleman@dtu.ox.ac.uk.
Amanda I AdlerDiabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LJ, UK.
Robert J MentzDuke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA.
Marat FudimDuke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA.
Naveed SattarSchool of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK.
Rury R HolmanDiabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LJ, UK.

Funding

MULTIDISCIPLINARY HEART &VASCULAR DISEASEST32HL007101 · DUKE UNIVERSITY · 1985 to 2005
$2.5M
American Heart Association 17MCPRP33460225British Heart Foundation RE/18/6/34217NHLBI NIH HHS T32 HL007101NIH HHS 5T32HL007101
6 · The paper itself

Abstract

backgroundThe objective of this study was to examine the degree to which conventional cardiovascular (CV) risk factor changes induced by once-weekly exenatide (EQW) might explain the placebo-controlled differences in CV outcomes observed in the Exenatide Study of Cardiovascular Event Lowering (EXSCEL).

methodsWe entered participant-level risk factor values over time into a validated type 2 diabetes-specific clinical outcomes model to estimate event rates, and compared simulated with observed relative risk changes in EXSCEL. We performed simulations for each participant to minimize uncertainty and to optimize confidence interval precision around risk point estimates. Six outcomes were examined: major adverse CV event (MACE), all-cause mortality (ACM), CV death, fatal or nonfatal myocardial infarction (MI), fatal or nonfatal stroke, and hospitalization for heart failure (hHF). We also performed a mediation analysis using Cox regression models to evaluate potential key mediators for ACM.

resultsModel simulations explained only modest proportions of the observed relative risk reductions for MACE (29%), ACM (15%), CV death (18%), and stroke (29%), but greater proportions for hHF (67%) and MI (200%). Mediation analysis suggested that baseline-to-6 or 12-month changes in HbA

conclusionsThese model simulations explain only a modest proportion of the impact of observed EQW-induced changes in conventional CV risk factors on EXSCEL outcomes, apart from hHF and MI. Up to 1-year changes in conventional risk factors did not mediate the observed ACM risk reduction.

Indexed as

Cardiovascular DiseasesDiabetes Mellitus, Type 2ExenatideGlucagon-Like Peptide-1 Receptor AgonistsHypoglycemic AgentsIncretinsAgedBiomarkersComputer SimulationDrug Administration ScheduleFemaleGlucagon-Like Peptide-1 ReceptorHeart Disease Risk FactorsHumansMaleMiddle AgedBiomarkersExenatideGLP1R protein, humanGlucagon-Like Peptide-1 ReceptorGlucagon-Like Peptide-1 Receptor AgonistsHypoglycemic AgentsIncretinsCardiovascular outcomesCardiovascular risk factorsGlucagon-like peptide-1 receptor agonistsMediation analysesModel simulationOnce-weekly exenatide

Identifiers

PMID40849664
PMCPMC12374271

What Socratic holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.