Evidence mapPaperPMID 31021474Full record

ReviewDiabetes/metabolism research and reviews2019

Mechanisms of action of metformin with special reference to cardiovascular protection.

Alexey V Zilov, Sulaf Ibrahim Abdelaziz, Afaf AlShammary, Ali Al Zahrani, Ashraf Amir, Samir Helmy Assaad Khalil, Kerstin Brand, Nabil Elkafrawy, Ahmed A K Hassoun, Adel Jahed and 3 more

Open access · hybridAbstract readReview
In one paragraph

Review in Diabetes/metabolism research and reviews, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 1 pooled it
9.2field-weighted citation impact, top 1% 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

36 citing papers in PubMed, 1 synthesis or guideline pooled it, 82 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Effects of the peripheral CBFrontiers in pharmacology · 2022
    Article
  15. Metformin Protects Cardiovascular Health in People With Diabetes.Frontiers in cardiovascular medicine · 2022
    Article
  16. Review
  17. Metformin Attenuates Cardiac HypertrophyFrontiers in pharmacology · 2022
    Article
  18. Single Nucleotide Polymorphism in the 3' Untranslated Region ofTherapeutics and clinical risk management · 2022
    Article
  19. Article
  20. 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

13 authors at 13 institutions in 10 countries.

Alexey V ZilovDepartment of Endocrinology, Sechenov's First Moscow State Medical University, Moscow, Russia.
Sulaf Ibrahim AbdelazizDepartment of Internal Medicine and Endocrinolgy, Soba University Hospital, Khartoum, Sudan.
Afaf AlShammaryDiabetes Center, Department of Medicine, King Abdulaziz Medical City, Riyadh, Kingdom of Saudi Arabia.
Ali Al ZahraniDepartment of Medicine, Molecular Endocrinology Section, Department of Molecular Oncology, Research Center, King Faisal Specialist Hospital & Research Centre, Riyadh, Kingdom of Saudi Arabia.
Ashraf AmirDepartment of Family Medicine, International Medical Center, Jeddah, Kingdom of Saudi Arabia.
Samir Helmy Assaad KhalilDepartment of Internal Medicine, Unit of Diabetology, Lipidology & Metabolism, Alexandria Faculty of Medicine, Alexandria University, Alexandria, Egypt.
Kerstin BrandGlobal Medical Affairs, Merck Healthcare KGaA, Darmstadt, Germany.
Nabil ElkafrawyDiabetes and Endocrinology Unit, Menoufia University, Al Minufya, Egypt.
Ahmed A K HassounDubai Diabetes Center, Dubai Health Authority, Dubai, United Arab Emirates.
Adel JahedGabric Diabetes Education Association, Tehran, Iran and Consultant Endocrinologist, Tehran General Hospital, Tehran, Iran.
Nadim JarrahInternal Medicine Department, The Specialty Hospital, Amman, Jordan.
Sanaa MrabetiGeneral Medicine and Endocrinology, Medical Affairs EMEA Merck Serono Middle East FZ-LLC, Dubai, United Arab Emirates.ORCID 0000-0003-4324-645X
Imran ParukDepartment of Diabetes and Endocrinology, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
Alexandria University · EGDubai Health Authority · AEIranian Orthopedic Association · IRKing Abdulaziz Medical City · SAKing Abdullah International Medical Research Center · SAKing Faisal Specialist Hospital & Research Centre · SAMenoufia University · EGMerck (Germany) · DEMerck Serono (Italy) · ITSechenov University · RUSpecialty Hospital, Jordan · JOUniversity of Khartoum · SDUniversity of KwaZulu-Natal · ZA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Management guidelines continue to identify metformin as initial pharmacologic antidiabetic therapy of choice for people with type 2 diabetes without contraindications, despite recent randomized trials that have demonstrated significant improvements in cardiovascular outcomes with newer classes of antidiabetic therapies. The purpose of this review is to summarize the current state of knowledge of metformin's therapeutic actions on blood glucose and cardiovascular clinical evidence and to consider the mechanisms that underlie them. The effects of metformin on glycaemia occur mainly in the liver, but metformin-stimulated glucose disposal by the gut has emerged as an increasingly import site of action of metformin. Additionally, metformin induces increased secretion of GLP-1 from intestinal L-cells. Clinical cardiovascular protection with metformin is supported by three randomized outcomes trials (in newly diagnosed and late stage insulin-treated type 2 diabetes patients) and a wealth of observational data. Initial evidence suggests that cotreatment with metformin may enhance the impact of newer incretin-based therapies on cardiovascular outcomes, an important observation as metformin can be combined with any other antidiabetic agent. Multiple potential mechanisms support the concept of cardiovascular protection with metformin beyond those provided by reduced blood glucose, including weight loss, improvements in haemostatic function, reduced inflammation, and oxidative stress, and inhibition of key steps in the process of atherosclerosis. Accordingly, metformin remains well placed to support improvements in cardiovascular outcomes, from diagnosis and throughout the course of type 2 diabetes, even in this new age of improved outcomes in type 2 diabetes.

Indexed as

Cardiovascular DiseasesDiabetes Mellitus, Type 2HumansHypoglycemic AgentsMetforminPrognosisHypoglycemic AgentsMetformincardiovascular outcomeshyperglycaemiametformintype 2 diabetes

Identifiers

PMID31021474
PMCPMC6851752
OpenAlexW2942046159

What Socratic holds

Texttitle and abstract
LicenceCC BY-NC-ND
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.