Trial reportBMJ (Clinical research ed.)2009

Combining insulin with metformin or an insulin secretagogue in non-obese patients with type 2 diabetes: 12 month, randomised, double blind trial.

Søren S Lund, Lise Tarnow, Merete Frandsen, Bente B Nielsen, Birgitte V Hansen, Oluf Pedersen, Hans-Henrik Parving, Allan A Vaag

Registry-linked trialOpen access · hybridAbstract readRandomized Controlled Trial
In one paragraph

Trial report in BMJ (Clinical research ed.), 2009. 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 reports registered trial NCT00118963. Cited by 20 papers, 2 of them syntheses that pooled it.

1number the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 2 pooled it
2.8field-weighted citation impact, top 10% 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 · t2d, obesityfeeds 3 cells of the map
Δ -2.51-4.07 to -0.95
Weight gain was less with metformin plus biphasic insulin aspart 70/30 than with repaglinide plus biphasic insulin aspart 70/30 (difference in mean body weight between treatments -2.51 kg, 95% confidence interval -4.07 to -0.95).

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, 12 find no difference, 8 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
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
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.

NCT00118963 phase4completed

Effect of Repaglinide Versus Metformin Treatment in Combination With Insulin Biasp30 (Novologmix 70/30) Predinner on Glycemic and Non-Glycemic Cardiovascular Risk-Factors in Non-Obese Patients With Type-2-Diabetes With Unsatisfactory Glycaemic Control With Oral Hypoglycaemic Agents

Ran2003Enrolled102Registered outcomes8Posted comparisons0ConditionsDiabetes Mellitus, Type 2ArmsInsulin BIAsp30 (Novolog 70/30), Metformin, Placebo-Metformin, Placebo-Repaglinide, Repaglinide
Open the trial in the graph
5 · Its place in the literature

Who cites it

20 citing papers in PubMed, 2 syntheses or guidelines pooled it, 42 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Article
  5. Article
  6. Comparative evaluation of biphasic insulin with metformin and triple oral hypoglycemic agents (OHA) in type 2 diabetes patients.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2020
    Article
  7. Article
  8. Review
  9. Review
  10. Review
  11. Article
  12. A Randomized Trial of Step-up Treatment with Premixed Insulin Lispro-50/50 vs. Aspart-70/30 in Patients with Type 2 Diabetes Mellitus.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2014
    Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Review
  20. Article
6 · The record

Corrections and comments

7 · Who and what money

Authors and funding

8 authors at 3 institutions in 3 countries.

Søren S LundSteno Diabetes Center, Gentofte, Denmark. sqrl@steno.dk
Lise Tarnow
Merete Frandsen
Bente B Nielsen
Birgitte V Hansen
Oluf Pedersen
Hans-Henrik Parving
Allan A Vaag
Novo Nordisk (Denmark) · DKSteno Diabetes Center · DKAarhus University · DK

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.

objectivesTo study the effect of insulin treatment in combination with metformin or an insulin secretagogue, repaglinide, on glycaemic regulation in non-obese patients with type 2 diabetes.

designRandomised, double blind, double dummy, parallel trial.

settingSecondary care in Denmark between 2003 and 2006.

participantsNon-obese patients (BMI </=27) with preserved beta cell function.

interventionsAfter a four month run-in period with repaglinide plus metformin combination therapy, patients with a glycated haemoglobin (HbA(1c)) concentration of 6.5% or more were randomised to repaglinide 6 mg or metformin 2000 mg. All patients also received biphasic insulin aspart 70/30 (30% soluble insulin aspart and 70% intermediate acting insulin aspart) 6 units once a day before dinner for 12 months. Insulin dose was adjusted aiming for a fasting plasma glucose concentration of 4.0-6.0 mmol/l. The target of HbA(1c) concentration was less than 6.5%. Treatment was intensified to two or three insulin injections a day if glycaemic targets were not reached.

main outcome measureHbA(1c) concentration.

resultsOf the 459 patients who were eligible, 102 were randomised, and 97 completed the trial. Patients had had type 2 diabetes for approximately 10 years. At the end of treatment, HbA(1c) concentration was reduced by a similar amount in the two treatment groups (insulin plus metformin: mean (standard deviation) HbA(1c) 8.15% (1.32) v 6.72% (0.66); insulin plus repaglinide: 8.07% (1.49) v 6.90% (0.68); P=0.177). Total daily insulin dose and risk of hypoglycaemia were also similar in the two treatment groups. Weight gain was less with metformin plus biphasic insulin aspart 70/30 than with repaglinide plus biphasic insulin aspart 70/30 (difference in mean body weight between treatments -2.51 kg, 95% confidence interval -4.07 to -0.95).

conclusionsIn non-obese patients with type 2 diabetes and poor glycaemic regulation on oral hypoglycaemic agents, overall glycaemic regulation with insulin in combination with metformin was equivalent to that with insulin plus repaglinide. Weight gain seemed less with insulin plus metformin than with insulin plus repaglinide.

trial registrationNCT00118963.

Indexed as

Blood GlucoseCarbamatesDiabetes Mellitus, Type 2Double-Blind MethodDrug Therapy, CombinationFemaleGlycated HemoglobinHumansHypoglycemiaHypoglycemic AgentsInsulinInsulin AspartMaleMetforminMiddle AgedPatient ComplianceBlood GlucoseCarbamatesGlycated HemoglobinHypoglycemic AgentsInsulinInsulin AspartMetforminPiperidinesrepaglinide

Identifiers

PMID19900993
PMCPMC2775102
OpenAlexW1976422603

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.