Evidence mapPaperPMID 41107882Full record

ArticleCardiovascular diabetology2025

Stratifying cardiovascular benefits from GLP-1RA: a multisource analysis of patient-level CVOT and real-world data using AI-driven methods.

Mario Luca Morieri, Enrico Longato, Veronica Sciannameo, Emily Donatiello, Paola Berchialla, Angelo Avogaro, Agostino Consoli, Gian Paolo Fadini

Abstract readMulticenter Study
In one paragraph

Article in Cardiovascular diabetology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

8 authors.

Mario Luca MorieriDepartment of Medicine, University of Padova, Via Giustiniani 2, Padova, 35128, Italy. marioluca.morieri@unipd.it.
Enrico LongatoDepartment of Information Engineering, University of Padova, Padova, Italy.
Veronica SciannameoCentre for Biostatistics, Epidemiology and Public Health, Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, Orbassano, Italy.
Emily DonatielloNovo Nordisk Italia, SpA, Roma, Italy.
Paola BerchiallaCentre for Biostatistics, Epidemiology and Public Health, Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, Orbassano, Italy.
Angelo AvogaroDepartment of Medicine, University of Padova, Via Giustiniani 2, Padova, 35128, Italy.
Agostino ConsoliDepartment of Medicine and Aging Sciences, "G. d'Annunzio" University of Chieti- Pescara, Chieti, Italy.
Gian Paolo FadiniDepartment of Medicine, University of Padova, Via Giustiniani 2, Padova, 35128, Italy. gianpaolo.fadini@unipd.it.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIt remains unclear whether certain individuals with type 2 diabetes (T2D) derive greater cardiovascular benefit from GLP-1 receptor agonists (GLP-1RAs). Here, we integrate individual-level data from cardiovascular outcome trials (CVOTs) and electronic health records (EHRs), applying machine learning methods to confirm the cardiovascular benefits of GLP-1RAs in real-world populations and to identify subgroups with enhanced treatment response.

methodsData from two CVOTs (LEADER and SUSTAIN-6) and a large real-world study (DARWIN-T2D) were analyzed. We first transposed the hazard ratio (HR) for 3-point major adverse cardiovascular event (3P-MACE) from CVOTs to the real-world population. Then, we used PRISM (Patient Response Identifiers for Stratified Medicine) against 3P-MACE reduction by GLP-1RA in a training/test setting. Findings were validated with external cohorts of new-users of GLP-1RA or comparators (DPP-4 inhibitors or basal insulin).

resultsDespite notable differences in clinical characteristics between CVOT and real-world patients, the real-world-transposed HRs for 3P-MACE closely paralleled those from CVOTs. PRISM identified subgroups with differential treatment responses, based on history of myocardial infarction (MI) or stroke and age. Participants aged over 71 years without MI/stroke (41% of the real-world population) had the greatest relative benefit (HR 0.46; 95% CI 0.24-0.89 in the test set) and a greater absolute risk reduction (ARR 4.5%, 95% CI 1.2-7.7) than other subgroups (Gail-Simon p = 0.02). The external validation cohort confirmed these results (HR 0.67; 95% CI 0.51-0.89 and ARR 3.8%, 95% CI 1.5-6.1) showing significant differences in absolute risk reduction (p < 0.05).

conclusionsThis study supports the integration of individual data from CVOT with those from EHR to confirm the transposition of results from CVOT to real-world populations, and enables the identification and validation of subgroups with greater cardiovascular benefits from cardioprotective treatment such as GLP-1RA treatment. This precision medicine approach represents a new framework for deploying cardiovascular prevention strategies in T2D.

Indexed as

Cardiovascular DiseasesDecision Support TechniquesDiabetes Mellitus, Type 2Glucagon-Like Peptide-1 Receptor AgonistsIncretinsMachine LearningAgedElectronic Health RecordsFemaleGlucagon-Like Peptide-1 ReceptorHeart Disease Risk FactorsHumansMaleMiddle AgedRisk AssessmentRisk FactorsGLP1R protein, humanGlucagon-Like Peptide-1 ReceptorGlucagon-Like Peptide-1 Receptor AgonistsIncretinsCardiovascular preventionGLP-1RAPrecision medicineRandomized clinical trialReal-world evidence

Identifiers

PMID41107882
PMCPMC12535053

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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.