Evidence mapPaperPMID 42387302Full record

Trial reportDiabetes, obesity & metabolism2026

Potential Mediators of Efpeglenatide's Cardiovascular Benefit: An Exploratory Analysis of the AMPLITUDE-O Trial.

Daniel Raaschou-Oddershede, Christine R Schwarz, Tanya Kovalova, Kelley R Branch, Stefano Del Prato, Carolyn S P Lam, Renato D Lopes, Richard Pratley, Julio Rosenstock, Naveed Sattar and 1 more

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in Diabetes, obesity & metabolism, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Trial
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

11 authors.

Daniel Raaschou-OddershedeInstitute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, UK.ORCID https://orcid.org/0000-0002-0591-3656
Christine R SchwarzDepartment of Clinical and Translational Research, Steno Diabetes Center Copenhagen, Herlev, Denmark.
Tanya KovalovaPopulation Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada.
Kelley R BranchUW Medicine Heart Institute, Seattle, Washington, USA.
Stefano Del PratoInterdisciplinary Research Center for Health Science, Sant'anna School of Advanced Studies, Pisa, Italy.
Carolyn S P LamNational Heart Centre Singapore and Duke-NUS Medical School, Singapore, Singapore.ORCID https://orcid.org/0000-0003-1903-0018
Renato D LopesDuke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA.
Richard PratleyAdventHealth Translational Research Institute, Orlando, Florida, USA.ORCID https://orcid.org/0000-0002-2912-1389
Julio RosenstockVelocity Clinical Research, Dallas, Texas, USA.ORCID https://orcid.org/0000-0001-8324-3275
Naveed SattarInstitute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, UK.ORCID https://orcid.org/0000-0002-1604-2593
Hertzel C GersteinPopulation Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada.ORCID https://orcid.org/0000-0001-8072-2836

Funding

Hanmi PharmaceuticalSanofi
6 · The paper itself

Abstract

aimsIn the AMPLITUDE O trial, efpeglenatide reduced major cardiovascular events by 27% in 4076 individuals with Type 2 diabetes and established cardiovascular or kidney disease compared to placebo during a median follow-up of 1.81 years. This exploratory mediation analysis evaluates the degree to which changes in measured clinical variables and biomarkers during the trial might explain the observed reduction in MACE. MATERIALS AND

methodsMeasured variables were considered potential mediators if they were significantly changed by the intervention. The hazard (95% CI) per 1-unit increase in each time-updated mediator (change from baseline or updated mean) was estimated using Cox models adjusted for the same variables as in the main AMPLITUDE-O results. Mediators whose hazard-ratio CIs excluded 1.0 were then included in the MACE Cox model to estimate how much of efpeglenatide's effect on MACE could be statistically explained by its effect on that mediator in uni- and multivariable analyses.

resultsChange in HbA1c, weight, pulse pressure, LDL cholesterol, urinary albumin: creatinine ratio (UACR), eGFR, heart rate, lipase and amylase were modified by efpeglenatide. Of these, univariable analyses showed that only changes in HbA1c, LDL cholesterol, UACR and amylase accounted for 14%, 11%, 16% and 10%, respectively, of the effect of efpeglenatide on MACE. In the multivariable analysis, LDL cholesterol together with UACR accounted for 29.6% mediation of this effect.

conclusionIn this post hoc analysis from the AMPLITUDE-O trial, changes in LDL cholesterol together with UACR but not weight were estimated to statistically account for a modest portion of the reduction in risk of MACE with efpeglenatide.

Indexed as

Cardiovascular DiseasesDiabetes Mellitus, Type 2Diabetic AngiopathiesDiabetic NephropathiesHypoglycemic AgentsAgedBiomarkersBlood PressureCholesterol, LDLFemaleGlycated HemoglobinHumansMaleMediation AnalysisMiddle AgedBiomarkersCholesterol, LDLGlycated Hemoglobinhemoglobin A1c protein, humanHypoglycemic Agentscardiovascular diseaseGLP‐1 analogueincretin therapyType 2 diabetes

Identifiers

PMID42387302
PMCPMC13448972

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

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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.