Evidence map›Metformin × body weight & composition›PMID 19307526›Full record

Trial reportArchives of internal medicine2009

Long-term effects of metformin on metabolism and microvascular and macrovascular disease in patients with type 2 diabetes mellitus.

Adriaan Kooy, Jolien de Jager, Philippe Lehert, Daniël Bets, Michiel G Wulffelé, Ab J M Donker, Coen D A Stehouwer

2 registry-linked trialsOpen access · greenAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in Archives of internal medicine, 2009. The graph read 3 numbers from its abstract, feeding 2 cells of the map, but none could be read as for or against, so it casts no vote. It reports registered trial NCT00375388. Cited by 160 papers, 19 of them syntheses that pooled it.

3numbers the graph read from it
0cells of the map it votes in
160citing papers in PubMed, 19 pooled it
14.8field-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.

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

Weight gainmetformin vs placebo, in nulldescribes a change within one group, not a comparison · hypertension, t2dfeeds one cell of the map
Δ -3.07-3.85 to -2.28.001
RESULTS: Metformin treatment prevented weight gain (mean weight gain, -3.07 kg [range, -3.85 to -2.28 kg]; P < .001), improved glycemic control (mean reduction in HbA(1c) level, 0.4% percentage point [95% CI, 0.55-0.25]; P < .001) (where CI indicates confidence interval), despite the aim of similar glycemic control in both groups, and reduced insulin requirements (mean reduction, 19.63 IU/d [95% CI, 24.91-14.36 IU/d]; P < .001).

The authors add: null

FeedsMetformin×body weight & composition
HbA(1c)metformin vs placebo, in nulldescribes a change within one group, not a comparison · hypertension, t2dfeeds one cell of the map
Δ -0.40-0.55 to -0.25.001
RESULTS: Metformin treatment prevented weight gain (mean weight gain, -3.07 kg [range, -3.85 to -2.28 kg]; P < .001), improved glycemic control (mean reduction in HbA(1c) level, 0.4% percentage point [95% CI, 0.55-0.25]; P < .001) (where CI indicates confidence interval), despite the aim of similar glycemic control in both groups, and reduced insulin requirements (mean reduction, 19.63 IU/d [95% CI, 24.91-14.36 IU/d]; P < .001).

The authors add: null

FeedsMetformin×glycemic control
Insulin requirementsmetformin vs placebo, in nulldescribes a change within one group, not a comparison · hypertension, t2dfeeds one cell of the map
Δ -19.6-24.9 to -14.4.001
RESULTS: Metformin treatment prevented weight gain (mean weight gain, -3.07 kg [range, -3.85 to -2.28 kg]; P < .001), improved glycemic control (mean reduction in HbA(1c) level, 0.4% percentage point [95% CI, 0.55-0.25]; P < .001) (where CI indicates confidence interval), despite the aim of similar glycemic control in both groups, and reduced insulin requirements (mean reduction, 19.63 IU/d [95% CI, 24.91-14.36 IU/d]; P < .001).

The authors add: null

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×body weight & composition

No readable resultOpen 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 itNot a counted family in this claim, so removing it changes nothing.
← favours the comparatorfavours the treatment →
0 · no effect
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
Effect of Metformin Added to Insulin on Glycemic Control Among Overwei…PMID 26624824 · 164 enrolled · 2013
Δ 17.05.00 to 29.0
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

This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.

Metformin×glycemic control

No readable resultOpen 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 itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
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

This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.

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.

NCT00375388 phase3completed

Study of Metformin HCL in Patients With Type 2 Diabetes Intensively Treated With Insulin: a Treatment Strategy for Insulin Resistance in Type 2 Diabetes Mellitus: a Randomized Controlled Trial

Ran1998Enrolled400Registered outcomes4Posted comparisons0ConditionsType 2 Diabetes MellitusArmsMetformin on top of intensive insulin therapy
PMID 12453950other papers from this trial
Open the trial in the graph
NCT04943692 phase3suspendedstarted 2021, after this paper: background citation

Efficacy and Safety of Metformin Glycinate Compared to Metformin Hydrochloride on the Progression of Type 2 Diabetes

Ran2021Enrolled500Registered outcomes13Posted comparisons0ConditionsType 2 DiabetesArmsMetformin glycinate, Metformin hydrochloride
PMID 18784090PMID 7895460PMID 8743335PMID 16026361PMID 11225659PMID 9742977PMID 20388897PMID 9428831PMID 17145742PMID 7601013PMID 14502106PMID 7306436other papers from this trial
Open the trial in the graph
5 · Its place in the literature

Who cites it

160 citing papers in PubMed, 19 syntheses or guidelines pooled it, 431 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Pooled it
  8. Pooled it
  9. Guideline
  10. Pooled it
  11. Pooled it
  12. Pooled it
  13. Pooled it
  14. Pooled it
  15. Pooled it
  16. Pooled it
  17. Pooled it
  18. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus.The Cochrane database of systematic reviews · 2010 · on this map
    Pooled it
  19. Guideline
  20. Trial

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

6 · The record

Corrections and comments

7 · Who and what money

Authors and funding

7 authors at 3 institutions in 3 countries.

Adriaan KooyDepartment of Internal Medicine and Bethesda Diabetes Research Center, RA Hoogeveen, the Netherlands. kooy.a@bethesda.nl
Jolien de Jager
Philippe Lehert
Daniël Bets
Michiel G Wulffelé
Ab J M Donker
Coen D A Stehouwer
General Department of Preventive Medicine · VNOphthalmology Associates (United States) · USZiekenhuis Bethesda · NL

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.

backgroundWe investigated whether metformin hydrochloride has sustained beneficial metabolic and (cardio) vascular effects in patients with type 2 diabetes mellitus (DM2).

methodsWe studied 390 patients treated with insulin in the outpatient clinics of 3 hospitals in a randomized, placebo-controlled trial with a follow-up period of 4.3 years. Either metformin hydrochloride, 850 mg, or placebo (1-3 times daily) was added to insulin therapy. The primary end point was an aggregate of microvascular and macrovascular morbidity and mortality. The secondary end points were microvascular and macrovascular morbidity and mortality, as separate aggregate scores. In addition, effects on hemoglobin A(1c) (HbA(1c)), insulin requirement, lipid levels, blood pressure, body weight, and body mass index were analyzed.

resultsMetformin treatment prevented weight gain (mean weight gain, -3.07 kg [range, -3.85 to -2.28 kg]; P < .001), improved glycemic control (mean reduction in HbA(1c) level, 0.4% percentage point [95% CI, 0.55-0.25]; P < .001) (where CI indicates confidence interval), despite the aim of similar glycemic control in both groups, and reduced insulin requirements (mean reduction, 19.63 IU/d [95% CI, 24.91-14.36 IU/d]; P < .001). Metformin was not associated with an improvement in the primary end point. It was, however, associated with an improvement in the secondary, macrovascular end point (hazard ratio, 0.61 (95% CI, 0.40-0.94; P = .02), which was partly explained by the difference in weight. The number needed to treat to prevent 1 macrovascular end point was 16.1 (95% CI, 9.2-66.6).

conclusionsMetformin, added to insulin in patients with DM2, improved body weight, glycemic control, and insulin requirements but did not improve the primary end point. Metformin did, however, reduce the risk of macrovascular disease after a follow-up period of 4.3 years. These sustained beneficial effects support the policy to continue metformin treatment after the introduction of insulin in any patient with DM2, unless contraindicated. Trial Registration ClinicalTrials.gov Identifier: NCT00375388.

Indexed as

AdultAgedAged, 80 and overBlood PressureDiabetes Mellitus, Type 2Diabetic AngiopathiesDrug Therapy, CombinationFemaleFollow-Up StudiesGlycated HemoglobinHumansHypoglycemiaHypoglycemic AgentsInsulinLipidsMaleGlycated HemoglobinHypoglycemic AgentsInsulinLipidsMetformin

Identifiers

PMID19307526
OpenAlexW2123424236

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.