Evidence map›Paper›PMID 42410649›Full record

SynthesisCardiovascular diabetology2026

Glucagon-like peptide-1 receptor agonists and major limb events in adults with type 2 diabetes and peripheral artery disease: a systematic review and meta-analysis of RCTs and cohort studies.

Paola Caruso, Nicole Di Martino, Miriam Longo, Lorenzo Scappaticcio, Giuseppe Bellastella, Maria Ida Maiorino, Katherine Esposito, Dario Giugliano

Abstract readSystematic ReviewMeta-AnalysisReview
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Cardiovascular diabetology, 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. 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

8 authors.

Paola CarusoDivision of Endocrinology and Metabolic Diseases, University Hospital, University of Campania Luigi Vanvitelli, Naples, Italy.ORCID 0000-0002-4756-2022
Nicole Di MartinoDivision of Endocrinology and Metabolic Diseases, University Hospital, University of Campania Luigi Vanvitelli, Naples, Italy.ORCID 0009-0001-8062-3958
Miriam LongoDepartment of Life Sciences, and Health and Health Professions, Link Campus University, Rome, Italy.ORCID 0000-0002-6459-5854
Lorenzo ScappaticcioDivision of Endocrinology and Metabolic Diseases, University Hospital, University of Campania Luigi Vanvitelli, Naples, Italy.ORCID 0009-0007-7628-2226
Giuseppe BellastellaDivision of Endocrinology and Metabolic Diseases, University Hospital, University of Campania Luigi Vanvitelli, Naples, Italy.ORCID 0000-0002-4748-321X
Maria Ida MaiorinoDivision of Endocrinology and Metabolic Diseases, University Hospital, University of Campania Luigi Vanvitelli, Naples, Italy.ORCID 0000-0003-4659-7546
Katherine EspositoDivision of Endocrinology and Metabolic Diseases, University Hospital, University of Campania Luigi Vanvitelli, Naples, Italy.ORCID 0000-0002-3652-5154
Dario GiuglianoDepartment of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy. dario.giugliano@unicampania.it.ORCID 0000-0002-9377-873X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe impact of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on peripheral artery disease (PAD) remains uncertain. We assessed the association between GLP-1RA use and major limb events in individuals with type 2 diabetes (T2D) and PAD.

methodsWe performed a literature search from inception to 31 March 2026 for randomized controlled trials and cohort studies comparing GLP-1RA use versus placebo, active comparators or non-use on lower limb outcomes in individuals with T2D and PAD. The primary outcome was a composite of major limb events, as defined by the investigators of the original studies included in the meta-analysis. Secondary outcomes included lower extremity amputation (LEA), revascularization, gangrene, major adverse cardiovascular events (MACE) and all-cause mortality. Subgroup analyses, leave-one-out sensitivity analyses, and meta-regression analysis were also performed.

resultsTwelve studies (2 RCTs and 10 matched cohort studies) with thirteen arms involving 418,282 participants were included. Treatment with GLP-1RAs was associated with a significantly lower risk of major limb events by 27% (thirteen arms, RR 0.73, 95% CI 0.65-0.82). Reduced risks were also observed for LEA (RR 0.76, 95% CI 0.66-0.87), revascularization (RR 0.81, 95% CI 0.77-0.86), gangrene (RR 0.80, 95% CI 0.77-0.85), MACE (RR 0.76, 95% CI 0.63-0.90) and all-cause mortality (RR 0.67, 95% CI 0.61-0.73). Subgroup and sensitivity analyses did not substantially change point estimates.

conclusionAmong adults with T2D and PAD, treatment with GLP-1RAs was associated with a lower risk of major limb events. There is a need of dedicated studies with standardized limb-specific endpoints to confirm the protective role of GLP-1RAs on limb events in people with T2D and PAD.

Indexed as

Diabetes Mellitus, Type 2Glucagon-Like Peptide-1 Receptor AgonistsHypoglycemic AgentsIncretinsPeripheral Arterial DiseaseAgedAmputation, SurgicalFemaleGlucagon-Like Peptide-1 ReceptorHumansLimb SalvageMaleMiddle AgedProtective FactorsRandomized Controlled Trials as TopicRisk AssessmentGLP1R protein, humanGlucagon-Like Peptide-1 ReceptorGlucagon-Like Peptide-1 Receptor AgonistsHypoglycemic AgentsIncretinsAll-cause mortalityGlucagon-like peptide-1 receptor agonistsMACEMajor limb eventsMeta-analysisPeripheral artery diseaseType 2 diabetes mellitus

Identifiers

PMID42410649
PMCPMC13617921

What Socratic holds

Textmetadata
Read underepoch 390

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.