Evidence map›Paper›PMID 28615149›Full record

Trial reportThe lancet. Diabetes & endocrinology2017

Cardiovascular and metabolic effects of metformin in patients with type 1 diabetes (REMOVAL): a double-blind, randomised, placebo-controlled trial.

John R Petrie, Nishi Chaturvedi, Ian Ford, Martijn C G J Brouwers, Nicola Greenlaw, Therese Tillin, Irene Hramiak, Alun D Hughes, Alicia J Jenkins, Barbara E K Klein and 7 more

Erratum issuedOpen access · greenAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The lancet. Diabetes & endocrinology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 166 papers, 10 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
166citing papers in PubMed, 10 pooled it
26.4field-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

166 citing papers in PubMed, 10 syntheses or guidelines pooled it, 340 citations in OpenAlex.

  1. Pooled it
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  5. Guideline
  6. Metformin for preventing the progression of chronic kidney disease.The Cochrane database of systematic reviews · 2024 · on this map
    Pooled it
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  11. Trial
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  14. Metformin Improves Peripheral Insulin Sensitivity in Youth With Type 1 Diabetes.The Journal of clinical endocrinology and metabolism · 2019
    Trial
  15. Trial
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  18. Article
  19. Obesity in Adults with Type 1 Diabetes Mellitus.Journal of obesity & metabolic syndrome · 2026
    Review
  20. Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 9 institutions in 6 countries.

John R PetrieInstitute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK. Electronic address: john.petrie@glasgow.ac.uk.
Nishi ChaturvediInstitute of Cardiovascular Science, University College London, London, UK.
Ian FordRobertson Centre for Biostatistics, University of Glasgow, Glasgow, UK.
Martijn C G J BrouwersDepartment of Internal Medicine and Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, Maastricht, Netherlands.
Nicola GreenlawRobertson Centre for Biostatistics, University of Glasgow, Glasgow, UK.
Therese TillinInstitute of Cardiovascular Science, University College London, London, UK.
Irene HramiakSt Joseph's Health Care, London, ON, Canada.
Alun D HughesInstitute of Cardiovascular Science, University College London, London, UK.
Alicia J JenkinsNHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia.
Barbara E K KleinUniversity of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Ronald KleinUniversity of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Teik C OoiOttawa Hospital Research Institute, The Ottawa Hospital, Ottawa, ON, Canada.
Peter RossingSteno Diabetes Center Copenhagen and University of Copenhagen, Copenhagen, Denmark.
Coen D A StehouwerDepartment of Internal Medicine and Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, Maastricht, Netherlands.
Naveed SattarInstitute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
Helen M ColhounInstitute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
REMOVAL Study Group
Institute of Genetics and Cancer · GBUniversity of Glasgow · GBMaastricht University Medical Centre · NLThe University of Sydney · AUOttawa Hospital · CAUniversity of Copenhagen · DKUniversity College London · GBUniversity of Wisconsin–Madison · USSt Joseph's Health Care · CA

Funding

British Heart Foundation CS/13/1/30327
6 · The paper itself

Abstract

backgroundMetformin might reduce insulin requirement and improve glycaemia in patients with type 1 diabetes, but whether it has cardiovascular benefits is unknown. We aimed to investigate whether metformin treatment (added to titrated insulin therapy) reduced atherosclerosis, as measured by progression of common carotid artery intima-media thickness (cIMT), in adults with type 1 diabetes at increased risk for cardiovascular disease.

methodsREMOVAL was a double-blind, placebo-controlled trial undertaken at 23 hospital diabetes clinics in five countries (Australia, Canada, Denmark, the Netherlands, and the UK). Adults aged 40 years and older with type 1 diabetes of at least 5 years' duration and at least three of ten specific cardiovascular risk factors were randomly assigned (via an interactive voice response system) to oral metformin 1000 mg twice daily or placebo. Participants and site staff were masked to treatment allocation. The primary outcome was averaged mean far-wall cIMT, quantified annually for 3 years, analysed in a modified intention-to-treat population (all randomly assigned participants with post-randomisation data available for the outcome of interest at any given timepoint, irrespective of subsequent adherence or study participation), using repeated measures regression. Secondary outcomes were HbA

findingsBetween Dec 14, 2011, and June 24, 2014, 493 participants entered a 3 month run-in to optimise risk factor and glycaemic control (single-blind placebo in the final month). Of 428 randomly assigned patients, 219 were allocated to metformin and 209 to placebo. Progression of mean cIMT was not significantly reduced with metformin (-0·005 mm per year, 95% CI -0·012 to 0·002; p=0·1664), although maximal cIMT (a prespecified tertiary outcome) was significantly reduced (-0·013 mm per year, -0·024 to -0·003; p=0·0093). HbA

interpretationThese data do not support use of metformin to improve glycaemic control in adults with long-standing type 1 diabetes as suggested by current guidelines, but suggest that it might have a wider role in cardiovascular risk management.

fundingJDRF.

Indexed as

AtherosclerosisCarotid Intima-Media ThicknessDiabetes Mellitus, Type 1Double-Blind MethodFemaleGlomerular Filtration RateHumansHypoglycemic AgentsMaleMetforminMiddle AgedRisk FactorsTreatment OutcomeHypoglycemic AgentsMetformin

Identifiers

PMID28615149
PMCPMC5641446
OpenAlexW2624031057

What Socratic holds

Texttitle and abstract
LicenceTDM
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.