Trial reportJournal of the American College of Cardiology2001
Improved endothelial function with metformin in type 2 diabetes mellitus.
Trial report in Journal of the American College of Cardiology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 152 papers, 2 of them syntheses 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.
The Effects of Metformin on Vascular Structure and Function in Subjects With the Metabolic Syndrome (MET Trial)
Open the trial in the graphExercise Dose and Metformin for Vascular Health in Adults With Metabolic Syndrome
Who cites it
152 citing papers in PubMed, 2 syntheses or guidelines pooled it, 512 citations in OpenAlex.
- Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus.The Cochrane database of systematic reviews · 2010 · on this mapPooled it
- [Metformin for type-2 diabetes mellitus. Systematic review and meta-analysis].Atencion primaria · 2005 · on this mapPooled it
- Twenty-Four week Taichi training improves pulmonary diffusion capacity and glycemic control in patients with Type 2 diabetes mellitus.PloS one · 2024Trial
- Effects of Long-term Metformin and Lifestyle Interventions on Cardiovascular Events in the Diabetes Prevention Program and Its Outcome Study.Circulation · 2022Trial
- A randomised placebo controlled trial of VSL#3BMC gastroenterology · 2021Trial
- Metformin may adversely affect orthostatic blood pressure recovery in patients with type 2 diabetes: substudy from the placebo-controlled Copenhagen Insulin and Metformin Therapy (CIMT) trial.Cardiovascular diabetology · 2020 · on this mapTrial
- A randomized controlled trial of metformin on left ventricular hypertrophy in patients with coronary artery disease without diabetes: the MET-REMODEL trial.European heart journal · 2019 · on this mapTrial
- Non-traditional biomarkers and incident diabetes in the Diabetes Prevention Program: comparative effects of lifestyle and metformin interventions.Diabetologia · 2019 · on this mapTrial
- The effects of vildagliptin compared with metformin on vascular endothelial function and metabolic parameters: a randomized, controlled trial (Sapporo Athero-Incretin Study 3).Cardiovascular diabetology · 2017Trial
- Effect of Long-Term Metformin and Lifestyle in the Diabetes Prevention Program and Its Outcome Study on Coronary Artery Calcium.Circulation · 2017Trial
- A randomised, active- and placebo-controlled, three-period crossover trial to investigate short-term effects of the dipeptidyl peptidase-4 inhibitor linagliptin on macro- and microvascular endothelial function in type 2 diabetes.Cardiovascular diabetology · 2017Trial
- Effect of metformin treatment on circulating osteoprotegerin in patients with nonalcoholic fatty liver disease.Hepatology international · 2016Trial
- Does metformin improve vascular health in children with type 1 diabetes? Protocol for a one year, double blind, randomised, placebo controlled trial.BMC pediatrics · 2013Trial
- Effects of metformin versus glipizide on cardiovascular outcomes in patients with type 2 diabetes and coronary artery disease.Diabetes care · 2013 · on this mapTrial
- Relation between augmentation index and adiponectin during one-year metformin treatment for nonalcoholic steatohepatosis: effects beyond glucose lowering?Cardiovascular diabetology · 2012Trial
- Short-term treatment with metformin improves the cardiovascular risk profile in first-degree relatives of subjects with type 2 diabetes mellitus who have a metabolic syndrome and normal glucose tolerance without changes in C-reactive protein or fibrinogen.Clinics (Sao Paulo, Brazil) · 2009Trial
- Oxidative stress and endothelium influenced by metformin in type 2 diabetes mellitus.European journal of clinical pharmacology · 2007 · on this mapTrial
- Spironolactone impairs endothelial function and heart rate variability in patients with type 2 diabetes.Diabetologia · 2004Trial
- Elevated serum galectin-3 levels predict the incidence of type 2 diabetes mellitus in a Japanese general population: A 10-year follow-up study.Journal of diabetes investigation · 2026Article
- Coronary Microvascular Dysfunction and Lipid Molecules: Pathophysiological Mechanisms, Clinical Assessment, and Therapeutic Implications.Journal of personalized medicine · 2026Review
92 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesThis study was designed to assess the effect of metformin on impaired endothelial function in type 2 diabetes mellitus.
backgroundAbnormalities in vascular endothelial function are well recognized among patients with type 2 (insulin-resistant) diabetes mellitus. Insulin resistance itself may be central to the pathogenesis of endothelial dysfunction. The effects of metformin, an antidiabetic agent that improves insulin sensitivity, on endothelial function have not been reported.
methodsSubjects with diet-treated type 2 diabetes but without the confounding collection of cardiovascular risk factors seen in the metabolic syndrome were treated with metformin 500 mg twice daily (n = 29) or placebo (n = 15) for 12 weeks. Before and after treatment, blood flow responses to intraarterial administration of endothelium-dependent (acetylcholine), endothelium-independent (sodium nitroprusside) and nitrate-independent (verapamil) vasodilators were measured using forearm plethysmography. Whole-body insulin resistance was assessed on both occasions using the homeostasis model (HOMA-IR).
resultsSubjects who received metformin demonstrated statistically significant improvement in acetylcholine-stimulated flows compared with those treated with placebo (p = 0.0027 by 2-way analysis of variance), whereas no significant effect was seen on nitroprusside-stimulated (p = 0.27) or verapamil-stimulated (p = 0.40) flows. There was a significant improvement in insulin resistance with metformin (32.5% reduction in HOMA-IR, p = 0.01), and by stepwise multivariate analysis insulin resistance was the sole predictor of endothelium-dependent blood flow following treatment (r = -0.659, p = 0.0012).
conclusionsMetformin treatment improved both insulin resistance and endothelial function, with a strong statistical link between these variables. This supports the concept of the central role of insulin resistance in the pathogenesis of endothelial dysfunction in type 2 diabetes mellitus. This has important implications for the investigation and treatment of vascular disease in patients with type 2 diabetes mellitus.
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.