Trial reportDiabetes, obesity & metabolism2017
Metformin in adults with type 1 diabetes: Design and methods of REducing with MetfOrmin Vascular Adverse Lesions (REMOVAL): An international multicentre trial.
Trial report in Diabetes, obesity & metabolism, 2017. The graph read 1 number from its abstract, feeding 1 cell of the map, but none could be read as for or against, so it casts no vote. Cited by 22 papers, 4 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.
Read, but not usablea number the graph found but could not read as for or against
This design provides 90% power to detect a mean difference of 0.0167 mm in cIMT progression between treatment arms (α = 0.05), assuming that up to 20% withdraw or discontinue treatment.
clause the extractor read what became the number
Where it lands on the map
Rows are treatments, columns are outcomes. The coloured squares are the cells this paper feeds, coloured by the vote it casts there. Click one to jump to what this paper adds to it.
What it adds to each cell
For every cell the paper feeds: the belief in the claim with and without this paper, and this paper's estimate drawn against every other readable study in the cell. The ringed dot is this paper.
Metformin×cardiac & vascular function
No readable resultOpen on the map →What to test next →4 readable studies in this cell: 1 favour the treatment, 3 find no difference, 0 favour the comparator.
This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.
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
22 citing papers in PubMed, 4 syntheses or guidelines pooled it, 40 citations in OpenAlex.
- Effect of Oral Hypoglycaemic Agents on Carotid Artery Intima-Media Thickness in Patients With Cardiovascular Disease and/or Diabetes-A Systematic Review.Endocrinology, diabetes & metabolism · 2025Pooled it
- Metformin for preventing the progression of chronic kidney disease.The Cochrane database of systematic reviews · 2024 · on this mapPooled it
- Age, sex, disease severity, and disease duration difference in placebo response: implications from a meta-analysis of diabetes mellitus.BMC medicine · 2020Pooled it
- Carotid Intima-Media Thickness Progression as Surrogate Marker for Cardiovascular Risk: Meta-Analysis of 119 Clinical Trials Involving 100 667 Patients.Circulation · 2020Pooled it
- Cardiovascular and metabolic effects of metformin in patients with type 1 diabetes (REMOVAL): a double-blind, randomised, placebo-controlled trial.The lancet. Diabetes & endocrinology · 2017Trial
- Metformin in adults with type 1 diabetes: Design and methods of REducing with MetfOrmin Vascular Adverse Lesions (REMOVAL): An international multicentre trial.Diabetes, obesity & metabolism · 2017 · on this mapTrial
- Cardiometabolic risk factors, peripheral arterial tonometry and metformin in adults with type 1 diabetes participating in the REducing with MetfOrmin Vascular Adverse Lesions trial.Diabetes & vascular disease researchTrial
- Metformin Ameliorates Cognitive Deficits and Neuroinflammation in a Mouse Model of Familial Hypercholesterolemia.Neurochemical research · 2026Article
- S100A9 exerts insulin-independent antidiabetic and anti-inflammatory effects.Science advances · 2024Article
- Repurposing Metformin for the Treatment of Atrial Fibrillation: Current Insights.Vascular health and risk management · 2024Review
- Metformin Impedes Oxidation of LDL In Vitro.Pharmaceutics · 2023Article
- Metformin's Mechanisms in Attenuating Hallmarks of Aging and Age-Related Disease.Aging and disease · 2022Article
- Reading between the (Genetic) Lines: How Epigenetics is Unlocking Novel Therapies for Type 1 Diabetes.Cells · 2020Review
- Metformin in patients with and without diabetes: a paradigm shift in cardiovascular disease management.Cardiovascular diabetology · 2019Review
- The early detection of atherosclerosis in type 1 diabetes: why, how and what to do about it.Cardiovascular endocrinology & metabolism · 2019Review
- The journey of metformin from glycaemic control to mTOR inhibition and the suppression of tumour growth.British journal of clinical pharmacology · 2019Review
- Acute renal metabolic effect of metformin assessed with hyperpolarised MRI in rats.Diabetologia · 2018Article
- Metformin: new insights into an archetypal cardiometabolic drug.Cardiovascular endocrinology · 2017Article
- Metformin and ageing: improving ageing outcomes beyond glycaemic control.Diabetologia · 2017Review
- A new perspective on metformin therapy in type 1 diabetes.Diabetologia · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 9 institutions in 6 countries.
Funding
Abstract
The marked sentences are the ones the graph read a number from.
aimsCardiovascular (CV) disease is a major cause of reduced life expectancy in type 1 diabetes (T1D). Intensive insulin therapy prevents CV complications but is constrained by hypoglycaemia and weight gain. Adjunct metformin reduces insulin dose requirement and stabilizes weight but there are no data on its cardiovascular effects. We have therefore initiated an international double-blind, randomized, placebo-controlled trial (REMOVAL: REducing with MetfOrmin Vascular Adverse Lesions in type 1 diabetes) to examine whether metformin reduces progression of atherosclerosis in adults with T1D. Individuals ≥40 years of age with T1D for ≥5 years are eligible if they have ≥3 of 10 specified CV risk factors. The enrolment target is 500 participants in 17 international centres. MATERIALS AND
methodsAfter 12 weeks of single-blind placebo-controlled run-in, participants with ≥ 70% adherence are randomized to metformin or matching placebo for 3 years with insulin titrated towards HbA1c 7.0% (53 mmol/mol). The primary endpoint is progression of averaged mean far wall common carotid intima-media thickness (cIMT) measured by ultrasonography at baseline, 12, 24 and 36 months. This design provides 90% power to detect a mean difference of 0.0167 mm in cIMT progression between treatment arms (α = 0.05), assuming that up to 20% withdraw or discontinue treatment. Other endpoints include HbA1c, weight, LDL cholesterol, insulin requirement, progression of retinopathy, endothelial function and frequency of hypoglycaemia.
conclusionREMOVAL is the largest clinical trial of adjunct metformin therapy in T1D to date and will provide clinically meaningful information on its potential to impact CV disease and other complications.
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.