Evidence map›Metformin × adverse events & safety›PMID 29040598›Full record

Trial reportThe Journal of clinical endocrinology and metabolism2017

Effect of Metformin on Vascular Function in Children With Type 1 Diabetes: A 12-Month Randomized Controlled Trial.

Jemma J A Anderson, Jennifer J Couper, Lynne C Giles, Catherine E Leggett, Roger Gent, Brian Coppin, Alexia S Peña

Open access · bronzeAbstract readRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in The Journal of clinical endocrinology and metabolism, 2017. The graph read 2 numbers from its abstract, feeding 2 cells of the map: it supports the treatment in 1, favours the comparator in 1. Cited by 34 papers, 6 of them syntheses that pooled it.

2numbers the graph read from it
2cells of the map it votes in
34citing papers in PubMed, 6 pooled it
5.7field-weighted citation impact, top 3% 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.

Ratios

← favours the treatmentfavours the comparator →
21 · no effect
Adverse events & safetyfavours the comparator · against placebo · ascvd, t1dfeeds one cell of the map
IRR 1.651.08 to 2.52P = 0.02
More gastrointestinal side effects were reported on metformin (incidence rate ratio 1.65, 95% CI 1.08, 2.52, P = 0.02), with no difference in hypoglycemia or diabetic ketoacidosis.
FeedsMetformin×adverse events & safety

Differences

← favours the treatmentfavours the comparator →
1.500 · no effect
Glycemic controlfavours the comparator · against placebo · ascvd, t1dfeeds one cell of the map
Δ 1.000.40 to 1.50P = 0.001
Metformin had a beneficial effect on HbA1c at 3 months (P = 0.001) and difference in adjusted HbA1c between groups during 12 months was 1.0%; 95% CI 0.4, 1.5 (10.9 mmol/mol; 95% CI 4.4, 16.4), P = 0.001.
FeedsMetformin×glycemic control

clause the extractor read what became the number

2 · Its place on the map

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.

supports the treatmentfavours the comparatorno clear differenceread, but no usable result
3 · What it changes

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×adverse events & safety

SupportsOpen on the map →What to test next →

22 readable studies in this cell: 8 favour the treatment, 8 find no difference, 6 favour the comparator.

Belief with this paper
0.27contested · 4 families support, 11 contradict · against placebo
Without it
0.21This paper moves it by +0.05.
← favours the treatmentfavours the comparator →
1 · no effect
This paper · 2017
IRR 1.651.08 to 2.52
NCT02932475831 enrolled · 2017
OR 0.860.63 to 1.19
NCT02980276535 enrolled · 2017
OR 0.530.27 to 1.01
Randomized Study of Metformin and Intensive Lifestyle Intervention on …PMID 40243198 · 2025
HR 0.900.73 to 1.10
Antidiabetic Drugs and Prostate Cancer Prognosis in a Finnish Populati…PMID 33653815 · 2021
HR 1.421.18 to 1.70

Metformin×glycemic control

ContradictsOpen on the map →What to test next →

40 readable studies in this cell: 41 favour the treatment, 13 find no difference, 7 favour the comparator.

Belief with this paper
0.84replicated · 32 families support, 6 contradict · against placebo
Without it
0.86This paper moves it by −0.02.
← favours the treatmentfavours the comparator →
0 · no effect
This paper · 2017
Δ 1.000.40 to 1.50
NCT017190031,413 enrolled · 2012
Adjusted mean -0.72-0.95 to -0.48
NCT018093271,186 enrolled · 2013
Δ -0.40-0.59 to -0.21
NCT022730501,136 enrolled · 2014
Δ -0.89-1.08 to -0.69
NCT008598981,093 enrolled · 2009
Δ -0.53-0.74 to -0.32
The study to understand the genetics of the acute response to metformi…PMID 25812009 · 1,033 enrolled · 2008
Δ -0.85-43.8 to 26.7
NCT00643851994 enrolled · 2008
Δ -0.86-1.11 to -0.62
NCT01708902876 enrolled · 2012
Δ -1.00-1.23 to -0.78
NCT00676338820 enrolled · 2008
Δ -0.05-0.26 to 0.17
NCT01126580807 enrolled · 2010
Δ -0.22-0.36 to -0.08
NCT01023581784 enrolled · 2009
Δ -0.67-0.96 to -0.37
NCT01076088744 enrolled · 2010
Δ -0.84-1.15 to -0.52
NCT00386100688 enrolled · 2006
Δ -0.49-0.67 to -0.30
4 · 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.

5 · Its place in the literature

Who cites it

34 citing papers in PubMed, 6 syntheses or guidelines pooled it, 62 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Trial
  8. Trial
  9. Trial
  10. Type 1 diabetes and cardiovascular medicine.Cardiovascular diabetology. Endocrinology reports · 2026
    Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Serum Concentrations and Dietary Intake of Vitamin BInternational journal of molecular sciences · 2023
    Article
  17. Review
  18. Review
  19. Review
  20. Article
6 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

7 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Jemma J A AndersonDiscipline of Paediatrics, Robinson Research Institute, University of Adelaide, Australia.
Jennifer J CouperDiscipline of Paediatrics, Robinson Research Institute, University of Adelaide, Australia.
Lynne C GilesSchool of Public Health, Faculty of Health and Medical Sciences, University of Adelaide, Australia.
Catherine E LeggettDiscipline of Paediatrics, Robinson Research Institute, University of Adelaide, Australia.
Roger GentMedical Imaging, Women's and Children's Hospital, Australia.
Brian CoppinFlinders Medical Centre, Bedford Park, Australia.
Alexia S PeñaDiscipline of Paediatrics, Robinson Research Institute, University of Adelaide, Australia.
University of Adelaide · AUWomen's and Children's Hospital · AUFlinders Medical Centre · AU

Funding

No grant is acknowledged in the PubMed record.

8 · The paper itself

Abstract

The marked sentences are the ones the graph read a number from.

Context: Children with type 1 diabetes have vascular dysfunction preceding atherosclerosis. Early interventions are needed to reduce cardiovascular disease. Objective: To evaluate the effect of metformin on vascular function in children with type 1 diabetes. Design: Twelve-month double-blind, randomized, placebo-controlled trial. Setting: Tertiary pediatric diabetes clinic. Participants: Ninety children (8 to 18 years of age), >50th percentile body mass index (BMI), with type 1 diabetes. Intervention: Metformin (up to 1 g twice a day) or placebo. Main Outcome Measure: Vascular function measured by brachial artery ultrasound [flow-mediated dilatation/glyceryl trinitrate-mediated dilatation (GTN)]. Results: Ninety participants were enrolled [41 boys, 13.6 (2.5) years of age, 45 per group], 10 discontinued intervention, and 1 was lost to follow-up. On metformin, GTN improved, independent of glycosylated hemoglobin (HbA1c), by 3.3 percentage units [95% confidence interval (CI) 0.3, 6.3, P = 0.03] and insulin dose reduced by 0.2 U/kg/d (95% CI 0.1, 0.3, P = 0.001) during 12 months, with effects from 3 months. Metformin had a beneficial effect on HbA1c at 3 months (P = 0.001) and difference in adjusted HbA1c between groups during 12 months was 1.0%; 95% CI 0.4, 1.5 (10.9 mmol/mol; 95% CI 4.4, 16.4), P = 0.001. There were no effects on carotid/aortic intima media thickness, BMI, lipids, blood pressure, or other cardiovascular risk factors. Median (95% CI) adherence, evaluated by electronic monitoring, was 75.5% (65.7, 81.5), without group differences. More gastrointestinal side effects were reported on metformin (incidence rate ratio 1.65, 95% CI 1.08, 2.52, P = 0.02), with no difference in hypoglycemia or diabetic ketoacidosis. Conclusions: Metformin improved vascular smooth muscle function and HbA1c, and lowered insulin dose in type 1 diabetes children. These benefits and good safety profile warrant further consideration of its use.

Indexed as

AdolescentBlood VesselsBrachial ArteryCardiovascular DiseasesChildDiabetes Mellitus, Type 1Diabetic AngiopathiesDouble-Blind MethodFemaleGlycated HemoglobinHumansHypoglycemic AgentsInsulinMaleMetforminNitroglycerinGlycated HemoglobinHypoglycemic AgentsInsulinMetforminNitroglycerin

Identifiers

PMID29040598
OpenAlexW2762525513

What OpenQuestion holds

Texttitle and abstract
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 OpenQuestion graph.