Evidence map›Paper›PMID 41259721›Full record

ArticleDiabetes care2026

Metabolic Improvement Mediates the Causal Relationship Between GLP-1 Receptor Agonists and Myocardial Infarction: A Mendelian Randomization and Mediation Analysis Study.

Jingkai Tong, Nana Li, Fang Hu, Yingying Yue

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PubMed Full text at PMC Publisher
In one paragraph

Article in Diabetes care, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
–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

4 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Observational
  3. Review
  4. 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

4 authors.

Jingkai TongDepartment of Endocrinology, Tianjin First Central Hospital, Tianjin, China.
Nana LiTeaching Research Department, Tianjin First Central Hospital, Tianjin, China.
Fang HuDepartment of Cardiology, Tianjin First Central Hospital, Tianjin, China.ORCID 0009-0006-2750-7145
Yingying YueClinical Laboratory, Tianjin First Central Hospital, Tianjin, China.

Funding

Foundation of China 82202802
6 · The paper itself

Abstract

objectiveGlucagon-like peptide 1 receptor agonists (GLP-1RAs) have cardiovascular benefits, but whether this is via metabolic improvements or direct effect remains controversial. This study aimed to explore the causal link between GLP-1RAs and myocardial infarction (MI) and quantify the contribution of metabolic improvements. RESEARCH DESIGN AND

methodsMendelian randomization (MR) was applied to assess the causal relationship between GLP-1RAs and MI, and two-step MR analysis was applied to quantify the mediating role of metabolic traits. The direct effect of GLP-1RAs on MI was evaluated by multivariate Mendelian randomization (MVMR). Genetic variants associated with GLP-1 receptor (GLP-1R) expression (proxying GLP-1RAs) were used as instrumental variables. Genome-wide association studies (GWAS) data for metabolic traits glycated hemoglobin (HbA1c), BMI, lipid profile, and blood pressure were sourced from the Million Veteran Program, serving as mediators. GWAS data for type 2 diabetes mellitus (T2DM) were obtained from the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium, and data for MI were sourced from the UK Biobank/Coronary ARtery DIsease Genome wide Replication and Meta-analysis plus The Coronary Artery Disease (CARDIoGRAMplusC4D), serving as outcomes. All GWAS data were restricted to European ancestry.

resultsHigher GLP-1R expression was correlated with a lower risk of T2DM (odds ratio 0.94 [95% CI 0.92, 0.97]) and MI (0.97 [0.95, 1.00]). Metabolic improvements mediated this association: HbA1c (36.67% [3.89, 69.44]), BMI (28.86% [2.62, 55.10]), triglycerides (18.52% [1.47, 35.57]), HDL-cholesterol (18.28% [1.45, 35.12]), and systolic blood pressure (11.55% [0.33, 22.76]). No direct effect of GLP-1R expression on MI was observed after adjusting for metabolic traits (β = -0.003, P = 0.12).

conclusionsGLP-1RAs protect against MI primarily through metabolic improvements, with no direct effect independent of these pathways. These findings support prioritizing metabolic improvements to reduce cardiovascular risk with GLP-1RAs.

Indexed as

Diabetes Mellitus, Type 2Glucagon-Like Peptide-1 Receptor AgonistsMyocardial InfarctionGenome-Wide Association StudyGlucagon-Like Peptide-1 ReceptorGlycated HemoglobinHumansMediation AnalysisMendelian Randomization AnalysisPolymorphism, Single NucleotideGlucagon-Like Peptide-1 ReceptorGlucagon-Like Peptide-1 Receptor AgonistsGlycated Hemoglobin

Identifiers

PMID41259721
PMCPMC12719715

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.