Evidence map›Paper›PMID 42063138›Full record

ArticleCardiovascular diabetology. Endocrinology reports2026

The long-term cardiovascular safety and efficacy of glucagon-like peptide-1 (GLP-1) receptor agonists in high-risk cardiovascular populations: a systematic review and meta-analysis.

Kezia Peter, Ocin Roka, Emma Sepp, Maya Warburton, Jufen Zhang, Simon C Cork

Abstract read
In one paragraph

Article in Cardiovascular diabetology. Endocrinology reports, 2026. 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. Which heart failure phenotypes benefit from GLP-1 receptor agonists?Cardiovascular diabetology. Endocrinology reports · 2026
    Article
  2. Article
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.

Kezia PeterSchool of Medicine, Anglia Ruskin University, Bishop Hall Road, Chelmsford, CM1 1SQ, UK.
Ocin RokaSchool of Medicine, Anglia Ruskin University, Bishop Hall Road, Chelmsford, CM1 1SQ, UK.
Emma SeppSchool of Medicine, Anglia Ruskin University, Bishop Hall Road, Chelmsford, CM1 1SQ, UK.
Maya WarburtonSchool of Medicine, Anglia Ruskin University, Bishop Hall Road, Chelmsford, CM1 1SQ, UK.
Jufen ZhangSchool of Medicine, Anglia Ruskin University, Bishop Hall Road, Chelmsford, CM1 1SQ, UK.
Simon C CorkSchool of Medicine, Anglia Ruskin University, Bishop Hall Road, Chelmsford, CM1 1SQ, UK. simon.cork@aru.ac.uk.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundGlucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for the management of type 2 diabetes and obesity, yet their long-term cardiovascular effects in high-risk populations continue to be actively evaluated. Given emerging evidence of both metabolic and direct cardiovascular actions, a comprehensive synthesis of cardiovascular outcome trial data is required to clarify the efficacy and safety of this drug class.

methodsWe conducted a systematic review and meta-analysis of randomised, placebo-controlled cardiovascular outcome trials evaluating GLP-1RAs in adults at high cardiovascular risk. Searches of PubMed, Embase (via OVID), and the Cochrane Library were performed for studies published between January 2015 and May 2025, in accordance with PRISMA 2020 guidelines. Eligible trials included ≥ 3,000 participants with a minimum follow-up of 12 months. The primary outcome was major adverse cardiovascular events (MACE). Secondary outcomes included cardiovascular mortality, all-cause mortality, non-fatal myocardial infarction, non-fatal stroke, hospitalisation for heart failure, and adverse events. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using random-effects meta-analysis. Risk of bias was assessed using the Cochrane RoB 2 tool, and certainty of evidence was evaluated using GRADE.

resultsEleven cardiovascular outcome trials comprising 91,490 participants were included, with a mean follow-up of 2.7 years. GLP-1RA treatment was associated with a significant reduction in MACE compared with placebo (HR 0.86, 95% CI 0.81-0.92). Meta-analysis also demonstrated significant reductions in cardiovascular mortality, all-cause mortality, non-fatal myocardial infarction, non-fatal stroke, and hospitalisation for heart failure. GLP-1RAs did not materially increase the risk of severe hypoglycaemia or acute pancreatitis, while gastrointestinal adverse effects were consistently more frequent.

conclusionsGLP-1 receptor agonists significantly reduce major cardiovascular events and mortality in high-risk populations, with a favourable long-term safety profile. These findings support the broader integration of GLP-1RAs into cardiovascular risk reduction strategies beyond glycaemic control.

Indexed as

CardioprotectionCardiovascular outcome trials (CVOTS)GLP-1 receptor agonistsMajor adverse cardiovascular events (MACE)Meta-analysisType 2 diabetes

Identifiers

PMID42063138
PMCPMC13134098

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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 OpenQuestion graph.