Evidence map›Paper›PMID 40926380›Full record

SynthesisDiabetes, obesity & metabolism2025

Cardiovascular risk reduction with glucagon-like peptide-1 receptor agonists is proportional to HbA1c lowering in type 2 diabetes: An updated meta-regression analysis incorporating FLOW and SOUL trials.

Masashi Hasebe, Chen-Yang Su, Yamato Keidai, Hiroto Minamino, Daisuke Yabe, Nobuya Inagaki, Satoshi Yoshiji

Abstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Diabetes, obesity & metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 4 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

8 citing papers in PubMed, 4 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Trial
  6. Article
  7. Article
  8. 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

7 authors.

Masashi HasebeCanada Excellence Research Chair in Genomic Medicine, McGill University, Montréal, Québec, Canada.ORCID https://orcid.org/0000-0001-7031-2446
Chen-Yang SuCanada Excellence Research Chair in Genomic Medicine, McGill University, Montréal, Québec, Canada.ORCID https://orcid.org/0000-0001-6071-4660
Yamato KeidaiDepartment of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan.ORCID https://orcid.org/0000-0001-6271-9609
Hiroto MinaminoDepartment of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan.ORCID https://orcid.org/0000-0002-9113-4690
Daisuke YabeDepartment of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan.ORCID https://orcid.org/0000-0002-5334-7687
Nobuya InagakiDepartment of Diabetes and Endocrinology, Medical Research Institute Kitano Hospital, PIIF Tazuke-Kofukai, Osaka, Japan.ORCID https://orcid.org/0000-0001-8261-2593
Satoshi YoshijiCanada Excellence Research Chair in Genomic Medicine, McGill University, Montréal, Québec, Canada.ORCID https://orcid.org/0000-0001-8863-2413

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsTo evaluate relationships of cardiovascular and kidney outcomes with glycemic or bodyweight reductions in randomised placebo-controlled trials of glucagon-like peptide-1 receptor agonists (GLP-1RAs), incorporating data from FLOW and SOUL trials. MATERIALS AND

methodsPubMed and EMBASE were searched up to 22 August 2025 for placebo-controlled randomized trials of oral or bolus-type, subcutaneous GLP-1RAs reporting major adverse cardiovascular events (MACE; a composite of cardiovascular death, myocardial infarction, and stroke) in adults with type 2 diabetes. The primary outcome was MACE; secondary outcomes included heart failure (HF) and kidney outcomes. Random-effects meta-analyses were followed by meta-regression evaluating associations with HbA1c and bodyweight reduction.

resultsA total of 73 263 individuals were included from 10 trials (ELIXA, LEADER, SUSTAIN-6, EXSCEL, Harmony Outcomes, PIONEER 6, REWIND, AMPLITUDE-O, FLOW, and SOUL). GLP-1RAs reduced MACE by 14% (hazard ratio: 0.86; 95% CI: 0.82 to 0.91; p <0.001), as well as hospitalisation for HF and the composite kidney outcome (both p <0.001). Meta-regression showed that every 1% extra reduction in HbA1c corresponded to a 27% lower HR for MACE (p = 0.015; R

conclusionsHbA1c reduction, not bodyweight change, was significantly and proportionally associated with MACE risk reduction. HbA1c lowering may serve as a useful surrogate for the cardiovascular improvements associated with GLP-1RAs in type 2 diabetes.

Indexed as

Cardiovascular DiseasesDiabetes Mellitus, Type 2Glucagon-Like Peptide-1 Receptor AgonistsGlycated HemoglobinHypoglycemic AgentsHumansRandomized Controlled Trials as TopicWeight LossGlucagon-Like Peptide-1 Receptor AgonistsGlycated Hemoglobinhemoglobin A1c protein, humanHypoglycemic Agentscardiovascular diseaseGLP‐1 receptor agonistsmeta‐analysistype 2 diabetes

Identifiers

PMID40926380
PMCPMC12587236

What Socratic holds

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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.