Evidence map›Metformin × glycemic control›PMID 26624824›Full record

Trial reportJAMA2015

Effect of Metformin Added to Insulin on Glycemic Control Among Overweight/Obese Adolescents With Type 1 Diabetes: A Randomized Clinical Trial.

Ingrid M Libman, Kellee M Miller, Linda A DiMeglio, Kathleen E Bethin, Michelle L Katz, Avni Shah, Jill H Simmons, Michael J Haller, Sripriya Raman, William V Tamborlane and 5 more

Registry-linked trialOpen access · bronzeAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in JAMA, 2015. The graph read 5 numbers from its abstract, feeding 3 cells of the map: it supports the treatment in 1, favours the comparator in 1, finds no clear difference in 1. It reports registered trial NCT01881828. Cited by 82 papers, 9 of them syntheses that pooled it.

5numbers the graph read from it
3cells of the map it votes in
82citing papers in PubMed, 9 pooled it
15.6field-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.

← favours the treatmentfavours the comparator →
-0.6051.00 · no effect
Reduction in HbA1cmetformin vs placebono clear difference · obesity, t1dfeeds one cell of the map
Δ -0.30-0.60 to 0.00P = .02
At 13-week follow-up, reduction in HbA1c was greater with metformin (-0.2%) than placebo (0.1%; mean difference, -0.3% [95% CI, -0.6% to 0.0%]; P = .02).
FeedsMetformin×glycemic control
Mean change in HbA1c from baselinemetformin vs placebono clear difference · obesity, t1dfeeds one cell of the map
Δ 0.00-0.30 to 0.30P = .92
However, this differential effect was not sustained at 26-week follow up when mean change in HbA1c from baseline was 0.2% in each group (mean difference, 0% [95% CI, -0.3% to 0.3%]; P = .92).
FeedsMetformin×glycemic control
Reduction in BMI z score of 10% or greater from baseline to 26 weeksmetformin vs placebofavours the comparator · obesity, t1dfeeds one cell of the map
Δ 17.05.00 to 29.0P = .01
At 26-week follow-up, total daily insulin per kg of body weight was reduced by at least 25% from baseline among 23% (16) of participants in the metformin group vs 1% (1) of participants in the placebo group (mean difference, 21% [95% CI, 11% to 32%]; P = .003), and 24% (17) of participants in the metformin group and 7% (5) of participants in the placebo group had a reduction in BMI z score of 10% or greater from baseline to 26 weeks (mean difference, 17% [95% CI, 5% to 29%]; P = .01).
FeedsMetformin×body weight & composition
Gastrointestinal adverse eventsmetformin vs placebofavours the comparator · obesity, t1dfeeds one cell of the map
Δ 36.019.0 to 51.0P < .001
Gastrointestinal adverse events were reported by more participants in the metformin group than in the placebo group (mean difference, 36% [95% CI, 19% to 51%]; P < .001).
FeedsMetformin×adverse events & safety

Read, but not usablea number the graph found but could not read as for or against

Total daily insulin per kg of body weight was reduced by at least 25% from baselinemetformin vs placebodirection of benefit for this outcome is not defined · obesity, t1dfeeds one cell of the map
Δ 21.011.0 to 32.0P = .003
At 26-week follow-up, total daily insulin per kg of body weight was reduced by at least 25% from baseline among 23% (16) of participants in the metformin group vs 1% (1) of participants in the placebo group (mean difference, 21% [95% CI, 11% to 32%]; P = .003), and 24% (17) of participants in the metformin group and 7% (5) of participants in the placebo group had a reduction in BMI z score of 10% or greater from baseline to 26 weeks (mean difference, 17% [95% CI, 5% to 29%]; P = .01).
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×glycemic control

InconclusiveOpen 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
0.84This paper does not move the number.
← favours the treatmentfavours the comparator →
0 · no effect
This paper164 enrolled · 2013
Δ 0.00-0.30 to 0.30
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

Metformin×body weight & composition

ContradictsOpen on the map →What to test next →

19 readable studies in this cell: 7 favour the treatment, 6 find no difference, 6 favour the comparator.

Belief with this paper
0.50contested · 8 families support, 4 contradict · against placebo
Without it
0.50This paper does not move the number.
← favours the treatmentfavours the comparator →
0 · no effect
This paper164 enrolled · 2013
Δ 17.05.00 to 29.0
NCT018093271,186 enrolled · 2013
Δ -0.90-1.60 to -0.20
NCT008598981,093 enrolled · 2009
Δ -1.37-2.03 to -0.71
NCT00643851994 enrolled · 2008
Δ -0.05-0.72 to 0.61
NCT02932475831 enrolled · 2017
Δ 0.04
NCT00676338820 enrolled · 2008
Δ -0.04-0.61 to 0.53
NCT02980276535 enrolled · 2017
Δ -0.70-1.30 to -0.20
Weight and Glucose Reduction Observed with a Combination of Nutritiona…PMID 27093610 · 53 enrolled · 2013
increase 1.26-0.24 to 2.75
A randomized, 48-week, placebo-controlled trial of intensive lifestyle…PMID 15302293 · 2004
weight loss -16.2-60.2 to -4.40
Efficacy and safety of ipragliflozin as an add-on therapy to sitaglipt…PMID 29862619 · 2018
Δ -1.72
Outcomes in children of women with type 2 diabetes exposed to metformi…PMID 36746160 · 2023
Δ 0.07-0.31 to 0.45
Effects of metformin on the body composition in subjects with risk fac…PMID 15715892 · 2005
increase 16.5
Metformin for the prevention of diabetes among people with HIV and eit…PMID 37460828 · 2023
Δ -1.47-2.58 to -0.35

Metformin×adverse events & safety

SupportsOpen on the map →What to test next →

22 readable studies in this cell: 9 favour the treatment, 8 find no difference, 5 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 →
0 · no effect
This paper164 enrolled · 2013
Δ 36.019.0 to 51.0
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 -8.90-13.3 to -4.50
NCT01126580807 enrolled · 2010
Δ -0.22-0.36 to -0.08
NCT01023581784 enrolled · 2009
Δ -0.67-0.96 to -0.37
NCT00386100688 enrolled · 2006
Δ 1.47-14.8 to 20.8
NCT01217073685 enrolled · 2010
Δ 1.00-9.80 to 13.1
NCT01890122647 enrolled · 2013
Δ -0.68-0.89 to -0.47
NCT00727857600 enrolled · 2007
Δ 0.860.51 to 1.22
NCT01958671461 enrolled · 2013
Δ -2.60-13.1 to 8.10
NCT00328172302 enrolled · 2006
Δ -0.85-1.10 to -0.59
NCT01485614200 enrolled · 2012
Δ 2.40-10.0 to 14.9
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.

NCT01881828 phase3completed

A Randomized Trial of Metformin as Adjunct Therapy for Overweight Adolescents With Type 1 Diabetes

Ran2013Enrolled164Registered outcomes16Posted comparisons0ConditionsType 1 DiabetesArmsMetformin (glucophage), oral placebo
PMID 22540912PMID 15855566PMID 18777487PMID 12502670PMID 23175691PMID 19996308PMID 20393934PMID 18721166PMID 12107742PMID 12702748PMID 12716791PMID 14514347other papers from this trial
Open the trial in the graph
5 · Its place in the literature

Who cites it

82 citing papers in PubMed, 9 syntheses or guidelines pooled it, 173 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Guideline
  7. Guideline
  8. Pooled it
  9. Drug interventions for the treatment of obesity in children and adolescents.The Cochrane database of systematic reviews · 2016
    Pooled it
  10. Trial
  11. Trial
  12. Trial
  13. Metformin Improves Peripheral Insulin Sensitivity in Youth With Type 1 Diabetes.The Journal of clinical endocrinology and metabolism · 2019
    Trial
  14. Trial
  15. Trial
  16. Trial
  17. Trial
  18. Article
  19. Review
  20. Review

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

6 · The record

Corrections and comments

7 · Who and what money

Authors and funding

15 authors at 12 institutions in 1 country.

Ingrid M LibmanChildren's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania.
Kellee M MillerJaeb Center for Health Research, Tampa, Florida.
Linda A DiMeglioIndiana University School of Medicine, Indianapolis.
Kathleen E BethinUniversity at Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York.
Michelle L KatzJoslin Diabetes Center, Boston, Massachusetts.
Avni ShahStanford University School of Medicine, Stanford, California.
Jill H SimmonsVanderbilt University, Nashville, Tennessee.
Michael J HallerUniversity of Florida, Gainesville.
Sripriya RamanChildren's Mercy Hospital, Kansas City, Missouri.
William V TamborlaneYale University, New Haven, Connecticut.
Julie K CoffeyUniversity of Iowa, Iowa City.
Ashleigh M SaenzJaeb Center for Health Research, Tampa, Florida.
Roy W BeckJaeb Center for Health Research, Tampa, Florida.
Kristen J NadeauUniversity of Colorado, Anschutz Medical Campus, Aurora.
T1D Exchange Clinic Network Metformin RCT Study Group
Jaeb Center for Health Research · USChildren's Hospital of Pittsburgh · USIndiana University School of MedicineJoslin Diabetes Center · USMercy Hospital · USStanford University · USUniversity at Buffalo, State University of New York · USUniversity of Colorado Anschutz Medical Campus · USUniversity of Florida · USUniversity of Iowa · USVanderbilt University · USYale University · US

Funding

NIDDK NIH HHS K12DK094721
8 · The paper itself

Abstract

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

importancePrevious studies assessing the effect of metformin on glycemic control in adolescents with type 1 diabetes have produced inconclusive results.

objectiveTo assess the efficacy and safety of metformin as an adjunct to insulin in treating overweight adolescents with type 1 diabetes. DESIGN, SETTING, AND

participantsMulticenter (26 pediatric endocrinology clinics), double-blind, placebo-controlled randomized clinical trial involving 140 adolescents aged 12.1 to 19.6 years (mean [SD] 15.3 [1.7] years) with mean type 1 diabetes duration 7.0 (3.3) years, mean body mass index (BMI) 94th (4) percentile, mean total daily insulin 1.1 (0.2) U/kg, and mean HbA1c 8.8% (0.7%).

interventionsRandomization to receive metformin (n = 71) (≤2000 mg/d) or placebo (n = 69). MAIN OUTCOMES AND MEASURES: Primary outcome was change in HbA1c from baseline to 26 weeks adjusted for baseline HbA1c. Secondary outcomes included change in blinded continuous glucose monitor indices, total daily insulin, BMI, waist circumference, body composition, blood pressure, and lipids.

resultsBetween October 2013 and February 2014, 140 participants were enrolled. Baseline HbA1c was 8.8% in each group. At 13-week follow-up, reduction in HbA1c was greater with metformin (-0.2%) than placebo (0.1%; mean difference, -0.3% [95% CI, -0.6% to 0.0%]; P = .02). However, this differential effect was not sustained at 26-week follow up when mean change in HbA1c from baseline was 0.2% in each group (mean difference, 0% [95% CI, -0.3% to 0.3%]; P = .92). At 26-week follow-up, total daily insulin per kg of body weight was reduced by at least 25% from baseline among 23% (16) of participants in the metformin group vs 1% (1) of participants in the placebo group (mean difference, 21% [95% CI, 11% to 32%]; P = .003), and 24% (17) of participants in the metformin group and 7% (5) of participants in the placebo group had a reduction in BMI z score of 10% or greater from baseline to 26 weeks (mean difference, 17% [95% CI, 5% to 29%]; P = .01). Gastrointestinal adverse events were reported by more participants in the metformin group than in the placebo group (mean difference, 36% [95% CI, 19% to 51%]; P < .001). CONCLUSIONS AND RELEVANCE: Among overweight adolescents with type 1 diabetes, the addition of metformin to insulin did not improve glycemic control after 6 months. Of multiple secondary end points, findings favored metformin only for insulin dose and measures of adiposity; conversely, use of metformin resulted in an increased risk for gastrointestinal adverse events. These results do not support prescribing metformin to overweight adolescents with type 1 diabetes to improve glycemic control.

trial registrationclinicaltrials.org Identifier: NCT01881828.

Indexed as

AdolescentBlood GlucoseBody Mass IndexBody WeightChildDiabetes Mellitus, Type 1Double-Blind MethodDrug Therapy, CombinationFemaleGastrointestinal DiseasesGlycated HemoglobinHumansHypoglycemic AgentsInsulinMaleMetforminBlood GlucoseGlycated HemoglobinHypoglycemic AgentsInsulinMetformin

Identifiers

PMID26624824
OpenAlexW2188909866

What Socratic holds

Texttitle and abstract
Read underepoch 390

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.