ReviewDiabetes/metabolism research and reviews2019
Mechanisms of action of metformin with special reference to cardiovascular protection.
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.
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.
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.
Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 82 citations in OpenAlex.
- Glucagon-like peptide-1 receptor agonist-based regimens compared with metformin-based regimens for preventing cardiovascular disease in adults with type 2 diabetes mellitus.The Cochrane database of systematic reviews · 2026Pooled it
- Heart Failure in Type 1 vs. Type 2 Diabetes Mellitus: Shared Pathways, Distinct Challenges.Journal of diabetes research · 2026Review
- Repurposing metformin for cardioprotection: mechanisms and therapeutic potential across cardiovascular pathologies.Frontiers in pharmacology · 2026Review
- Metformin in polycystic ovary syndrome: unraveling multi-stage therapeutic mechanisms from puberty to long-term health outcomes.Frontiers in pharmacology · 2025Review
- Overexpression of miR-199b-5p in Colony Forming Unit-Hill's Colonies Positively Mediates the Inflammatory Response in Subclinical Cardiovascular Disease Model: Metformin Therapy Attenuates Its Expression.International journal of molecular sciences · 2024Article
- Review
- Article
- Consumption of ultra-processed foods and risk of multimorbidity of cancer and cardiometabolic diseases: a multinational cohort study.The Lancet regional health. Europe · 2023Article
- Association of low-level lead exposure with all-cause and cardiovascular disease mortality in US adults with hypertension: evidence from the National Health and Nutrition Examination Survey 2003-2010.Archives of public health = Archives belges de sante publique · 2023Article
- Metformin alleviates ethanol-induced cardiomyocyte injury by activating AKT/Nrf2 signaling in an ErbB2-dependent manner.Molecular biology reports · 2023Article
- Metformin Suppresses Thioacetamide-Induced Chronic Kidney Disease in Association with the Upregulation of AMPK and Downregulation of Oxidative Stress and Inflammation as Well as Dyslipidemia and Hypertension.Molecules (Basel, Switzerland) · 2023Article
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- Effect of liraglutide combined with metformin or acarbose on glucose control in type 2 diabetes mellitus and risk factors of gastrointestinal adverse reactions.American journal of translational research · 2022Article
- Effects of the peripheral CBFrontiers in pharmacology · 2022Article
- Metformin Protects Cardiovascular Health in People With Diabetes.Frontiers in cardiovascular medicine · 2022Article
- 7,8-Dihydroxyflavone and Neuropsychiatric Disorders: A Translational Perspective from the Mechanism to Drug Development.Current neuropharmacology · 2022Review
- Metformin Attenuates Cardiac HypertrophyFrontiers in pharmacology · 2022Article
- Single Nucleotide Polymorphism in the 3' Untranslated Region ofTherapeutics and clinical risk management · 2022Article
- The Effects of Separate and Combined Treatment of Male Rats with Type 2 Diabetes with Metformin and Orthosteric and Allosteric Agonists of Luteinizing Hormone Receptor on Steroidogenesis and Spermatogenesis.International journal of molecular sciences · 2021Article
- Metformin for Cardiovascular Protection, Inflammatory Bowel Disease, Osteoporosis, Periodontitis, Polycystic Ovarian Syndrome, Neurodegeneration, Cancer, Inflammation and Senescence: What Is Next?ACS pharmacology & translational science · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 13 institutions in 10 countries.
Funding
No grant is acknowledged in the PubMed record.
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
Identifiers
What Socratic holds
Registered trials
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.