Evidence map›Insulin × glycemic control›PMID 10068412›Full record

Trial reportAnnals of internal medicine1999

Comparison of bedtime insulin regimens in patients with type 2 diabetes mellitus. A randomized, controlled trial.

H Yki-Järvinen, L Ryysy, K Nikkilä, T Tulokas, R Vanamo, M Heikkilä

Registry-linked trialAbstract readClinical TrialComparative StudyRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in Annals of internal medicine, 1999. The graph read 1 number from its abstract, feeding 3 cells of the map, but none could be read as for or against, so it casts no vote. It is linked to trial NCT02026310 (Efficacy/Safety Study of Adding Glimepiride to Type 2 Diabetes Patients With Inadequate Glycemic Control Based on Combination With Metformin And Basal Insulin), which is not on this map. Cited by 83 papers, 9 of them syntheses that pooled it.

1number the graph read from it
0cells of the map it votes in
83citing papers in PubMed, 9 pooled it
15.7field-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

Glycemic controlcomparator not stated · ckd, hypertensionfeeds 3 cells of the map
mean change 1.20P < 0.001
RESULTS: At 1 year, body weight remained unchanged in patients receiving bedtime insulin plus metformin (mean change, 0.9 +/- 1.2 kg; P < 0.001 compared with all other groups) but increased by 3.9 +/- 0.7 kg, 3.6 +/- 1.2 kg, and 4.6 +/- 1.0 kg in patients receiving bedtime insulin plus glyburide, those receiving bedtime insulin plus both oral drugs, and those receiving bedtime and morning insulin, respectively.
FeedsMetformin×glycemic controlSulfonylureas & glinides×glycemic controlInsulin×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.

Insulin×glycemic control

No readable resultOpen on the map →What to test next →

40 readable studies in this cell: 15 favour the treatment, 14 find no difference, 14 favour the comparator.

Belief with this paper
0.50contested · 9 families support, 6 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the comparatorfavours the treatment →
0 · no effect
NCT036893742,274 enrolled · 2018
Δ -0.29-0.38 to -0.20
NCT037306622,002 enrolled · 2018
Δ -0.99-1.13 to -0.86
NCT013360231,663 enrolled · 2011
Treatment contrast -0.64-0.75 to -0.53
NCT038829701,444 enrolled · 2019
Δ -0.86-1.00 to -0.72
NCT045379231,428 enrolled · 2020
Δ -1.10-1.24 to -0.97
NCT032680051,264 enrolled · 2017
Δ -0.04-0.11 to 0.03
NCT020581471,170 enrolled · 2014
Δ -0.78-0.90 to -0.67
NCT021289321,089 enrolled · 2014
Δ -0.81-0.96 to -0.67
NCT009606611,036 enrolled · 2009
Δ -0.04-0.18 to 0.11
NCT00856986987 enrolled · 2009
Δ -0.52-0.68 to -0.36
NCT01117350978 enrolled · 2010
Δ 2.54-3.88 to 8.93
NCT03214380933 enrolled · 2017
Δ 0.06-0.05 to 0.16

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.

Sulfonylureas & glinides×glycemic control

No readable resultOpen on the map →What to test next →

31 readable studies in this cell: 7 favour the treatment, 13 find no difference, 11 favour the comparator.

Belief with this paper
0.83established · 5 families support, 1 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the comparatorfavours the treatment →
0 · no effect
NCT017093055,570 enrolled · 2012
Δ 0.190.02 to 0.36
NCT009688121,452 enrolled · 2009
Δ -0.01-0.11 to 0.09
NCT006609071,217 enrolled · 2008
Δ 0.00-0.11 to 0.11
NCT003184611,091 enrolled · 2006
Δ -0.02-0.19 to 0.15
NCT008389031,049 enrolled · 2009
Δ -0.27-0.45 to -0.09
The study to understand the genetics of the acute response to metformi…PMID 25812009 · 1,033 enrolled · 2008
Δ 0.640.33 to 0.95
NCT03332771954 enrolled · 2017
Δ 0.12-0.12 to 0.36
NCT02471404939 enrolled · 2015
Δ 0.160.03 to 0.30
NCT00614120929 enrolled · 2008
Δ -0.06-0.23 to 0.11
NCT00575588891 enrolled · 2007
Δ 0.06-0.05 to 0.16
NCT01682759751 enrolled · 2012
Δ 0.180.06 to 0.30
NCT00294723746 enrolled · 2006
Δ -0.62-0.83 to -0.42

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.

NCT02026310 nacompletedstarted 2014, after this paper: background citation

Efficacy/Safety Study of Adding Glimepiride to Type 2 Diabetes Patients With Inadequate Glycemic Control Based on Combination With Metformin And Basal Insulin

Ran2014Enrolled40Registered outcomes2Posted comparisons0ConditionsDiabetes Mellitus, Type 2Armsglargine and metformin, Glimepiride
PMID 18784090PMID 20335585PMID 12401758PMID 20445742other papers from this trial
Open the trial in the graph
5 · Its place in the literature

Who cites it

83 citing papers in PubMed, 9 syntheses or guidelines pooled it, 431 citations in OpenAlex.

  1. Pooled it
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  5. Pooled it
  6. Guideline
  7. 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
  8. Guideline
  9. Pooled it
  10. Trial
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  19. Review
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23 more citing papers are in PubMed but not listed here.

6 · The record

Corrections and comments

7 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

H Yki-JärvinenUniversity of Helsinki, Finland.
L Ryysy
K Nikkilä
T Tulokas
R Vanamo
M Heikkilä
Lapland Central Hospital · FI

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.

backgroundCompared with other insulin regimens, combination therapy with oral hypoglycemic agents and bedtime insulin produces similar improvement in glycemic control but induces less weight gain.

objectiveTo determine whether bedtime insulin regimens differ with respect to their effects on weight gain in patients with type 2 diabetes.

designRandomized, controlled trial.

settingFour outpatient clinics at central hospitals. PATIENTS: 96 patients (mean age, 58 +/- 1 years; mean body mass index, 29 +/- 1 kg/m2) whose type 2 diabetes was poorly controlled with sulfonylurea therapy (mean glycosylated hemoglobin value, 9.9% +/- 0.2%; mean fasting plasma glucose level, 11.9 +/- 0.3 mmol/L [214 +/- 5 mg/dL]).

interventionRandom assignment to 1 year of treatment with bedtime intermediate-acting insulin plus glyburide (10.5 mg) and placebo, metformin (2 g) and placebo, glyburide and metformin, or a second injection of intermediate-acting insulin in the morning. Patients were taught to adjust the bedtime insulin dose on the basis of fasting glucose measurements. MEASUREMENTS: Body weight, biochemical and symptomatic hypoglycemias, and indices of glycemic control.

resultsAt 1 year, body weight remained unchanged in patients receiving bedtime insulin plus metformin (mean change, 0.9 +/- 1.2 kg; P < 0.001 compared with all other groups) but increased by 3.9 +/- 0.7 kg, 3.6 +/- 1.2 kg, and 4.6 +/- 1.0 kg in patients receiving bedtime insulin plus glyburide, those receiving bedtime insulin plus both oral drugs, and those receiving bedtime and morning insulin, respectively. The greatest decrease in the glycosylated hemoglobin value was observed in the bedtime insulin and metformin group (from 9.7% +/- 0.4% to 7.2% +/- 0.2% [difference, -2.5 +/- 0.4 percentage points] at 1 year; P < 0.001 compared with 0 months and P < 0.05 compared with other groups). This group also had significantly fewer symptomatic and biochemical cases of hypoglycemia (P < 0.05) than the other groups.

conclusionsCombination therapy with bedtime insulin plus metformin prevents weight gain. This regimen also seems superior to other bedtime insulin regimens with respect to improvement in glycemic control and frequency of hypoglycemia.

Indexed as

AlbuminuriaBlood GlucoseBlood PressureC-PeptideDiabetes Mellitus, Type 2Drug Administration ScheduleDrug Therapy, CombinationFollow-Up StudiesGlyburideGlycated HemoglobinHumansHypoglycemic AgentsInsulinLipidsMetforminMiddle AgedBlood GlucoseC-PeptideGlyburideGlycated HemoglobinHypoglycemic AgentsInsulinLipidsMetformin

Identifiers

PMID10068412
OpenAlexW1981978041

What Socratic holds

Texttitle and abstract
measurements read15
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.