Evidence map›Paper›PMID 34646376›Full record

ReviewTheranostics2021

Metformin in cardiovascular diabetology: a focused review of its impact on endothelial function.

Yu Ding, Yongwen Zhou, Ping Ling, Xiaojun Feng, Sihui Luo, Xueying Zheng, Peter J Little, Suowen Xu, Jianping Weng

Open access · goldFull text readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Theranostics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed, 2 pooled it
4.8field-weighted citation impact, top 4% of its field
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

61 citing papers in PubMed, 2 syntheses or guidelines pooled it, 94 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
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  6. Article
  7. Review
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  13. Diabetes and cancer: therapeutic implications.Cardio-oncology (London, England) · 2026
    Review
  14. Article
  15. Therapeutical progress in sepsis-induced cardiomyopathy.Frontiers in cardiovascular medicine · 2026
    Review
  16. Article
  17. Review
  18. Review
  19. Review
  20. Review

1 more citing papers are in PubMed but not listed here.

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

9 authors at 2 institutions in 2 countries.

Yu DingInstitute of Endocrine and Metabolic Diseases, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Yongwen ZhouInstitute of Endocrine and Metabolic Diseases, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Ping LingInstitute of Endocrine and Metabolic Diseases, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Xiaojun FengDepartment of Pharmacy, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Sihui LuoInstitute of Endocrine and Metabolic Diseases, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Xueying ZhengInstitute of Endocrine and Metabolic Diseases, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Peter J LittleSunshine Coast Health Institute, University of the Sunshine Coast, Birtinya, QLD 4575, Australia.
Suowen XuInstitute of Endocrine and Metabolic Diseases, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Jianping WengInstitute of Endocrine and Metabolic Diseases, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
University of Science and Technology of China · CNUniversity of the Sunshine Coast · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

As a first-line treatment for diabetes, the insulin-sensitizing biguanide, metformin, regulates glucose levels and positively affects cardiovascular function in patients with diabetes and cardiovascular complications. Endothelial dysfunction (ED) represents the primary pathological change of multiple vascular diseases, because it causes decreased arterial plasticity, increased vascular resistance, reduced tissue perfusion and atherosclerosis. Caused by "biochemical injury", ED is also an independent predictor of cardiovascular events. Accumulating evidence shows that metformin improves ED through liver kinase B1 (LKB1)/5'-adenosine monophosphat-activated protein kinase (AMPK) and AMPK-independent targets, including nuclear factor-kappa B (NF-κB), phosphatidylinositol 3 kinase-protein kinase B (PI3K-Akt), endothelial nitric oxide synthase (eNOS), sirtuin 1 (SIRT1), forkhead box O1 (FOXO1), krüppel-like factor 4 (KLF4) and krüppel-like factor 2 (KLF2). Evaluating the effects of metformin on endothelial cell functions would facilitate our understanding of the therapeutic potential of metformin in cardiovascular diabetology (including diabetes and its cardiovascular complications). This article reviews the physiological and pathological functions of endothelial cells and the intact endothelium, reviews the latest research of metformin in the treatment of diabetes and related cardiovascular complications, and focuses on the mechanism of action of metformin in regulating endothelial cell functions.

Indexed as

AMP-Activated Protein Kinase KinasesAMP-Activated Protein KinasesAnimalsCardiovascular DiseasesDiabetes ComplicationsDiabetes MellitusEndothelial CellsEndotheliumEndothelium, VascularForkhead Box Protein O1HumansHypoglycemic AgentsInsulinKruppel-Like Factor 4Kruppel-Like Transcription FactorsMetforminAKT1 protein, humanAMP-Activated Protein Kinase KinasesAMP-Activated Protein KinasesForkhead Box Protein O1Hypoglycemic AgentsInsulinKruppel-Like Factor 4Kruppel-Like Transcription FactorsMetforminNF-kappa BNitric Oxide Synthase Type IIIPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktSirtuin 1STK11 protein, humancardiovascular diabetologydiabetesendothelial functionMetforminpanvascular disease

Identifiers

PMID34646376
PMCPMC8490502
OpenAlexW3203761723

What Socratic holds

Textfull text, public
LicenceCC BY
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.