Evidence map›GLP-1 receptor agonists × glycemic control›PMID 19515413›Full record

Trial reportLancet (London, England)2009

Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6).

John B Buse, Julio Rosenstock, Giorgio Sesti, Wolfgang E Schmidt, Eduard Montanya, Jason H Brett, Marcin Zychma, Lawrence Blonde, LEAD-6 Study Group

2 registry-linked trialsAbstract readComparative StudyMulticenter StudyRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in Lancet (London, England), 2009. The graph read 3 numbers from its abstract, feeding 2 cells of the map: it . It reports registered trial NCT00518882. Cited by 536 papers, 15 of them syntheses that pooled it.

3numbers the graph read from it
2cells of the map it votes in
536citing papers in PubMed, 15 pooled it
101.3field-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.

Ratios

← favours the treatmentfavours the comparator →
0.51 · no effect
Glycemic controlfavours the treatment · head-to-head · t2d, obesityfeeds one cell of the map
IRR 0.550.34 to 0.88p=0.0131
Both drugs were well tolerated, but nausea was less persistent (estimated treatment rate ratio 0.448, p<0.0001) and minor hypoglycaemia less frequent with liraglutide than with exenatide (1.93 vs 2.60 events per patient per year; rate ratio 0.55; 95% CI 0.34 to 0.88; p=0.0131; 25.5%vs 33.6% had minor hypoglycaemia).
FeedsGLP-1 receptor agonists×glycemic control

Differences

← favours the comparatorfavours the treatment →
-1.370.450 · no effect
Adverse events & safetyfavours the treatment · head-to-head · t2d, obesityfeeds one cell of the map
IRR 0.45p<0.0001
Both drugs were well tolerated, but nausea was less persistent (estimated treatment rate ratio 0.448, p<0.0001) and minor hypoglycaemia less frequent with liraglutide than with exenatide (1.93 vs 2.60 events per patient per year; rate ratio 0.55; 95% CI 0.34 to 0.88; p=0.0131; 25.5%vs 33.6% had minor hypoglycaemia).
FeedsGLP-1 receptor agonists×adverse events & safety
Glycemic controlfavours the treatment · head-to-head · t2d, obesityfeeds one cell of the map
Δ -1.01-1.37 to -0.65p<0.0001
Liraglutide reduced mean fasting plasma glucose more than did exenatide (-1.61 mmol/L [SE 0.20] vs -0.60 mmol/L [0.20]; estimated treatment difference -1.01 mmol/L; 95% CI -1.37 to -0.65; p<0.0001) but postprandial glucose control was less effective after breakfast and dinner.
FeedsGLP-1 receptor agonists×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.

GLP-1 receptor agonists×glycemic control

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

40 readable studies in this cell: 96 favour the treatment, 17 find no difference, 10 favour the comparator.

Belief with this paper
0.91replicated · 68 families support, 7 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
1 · no effect
This paper467 enrolled · 2007
IRR 0.550.34 to 0.88
NCT035964501,278 enrolled · 2018
Treatment effect 1.361.03 to 1.79

GLP-1 receptor agonists×adverse events & safety

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

40 readable studies in this cell: 47 favour the treatment, 14 find no difference, 2 favour the comparator.

Belief with this paper
0.02contested · 1 family supports, 41 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
NCT017204463,297 enrolled · 2013
Δ -0.66-0.80 to -0.52
NCT036893742,274 enrolled · 2018
Δ -0.29-0.38 to -0.20
NCT013360231,663 enrolled · 2011
Treatment contrast -0.64-0.75 to -0.53
NCT040178321,441 enrolled · 2019
Δ -0.20-0.30 to -0.10
NCT018365231,398 enrolled · 2013
Δ -0.20-0.32 to -0.07
NCT019301881,231 enrolled · 2013
Δ -1.06-1.21 to -0.91
NCT007344741,202 enrolled · 2008
Δ -0.71-0.87 to -0.55
NCT008389031,049 enrolled · 2009
Δ -0.91-1.16 to -0.65
NCT009606611,036 enrolled · 2009
Δ -0.04-0.18 to 0.11
NCT050350821,018 enrolled · 2021
Δ -0.24-0.44 to -0.04
NCT01064687978 enrolled · 2010
Δ -1.05-1.22 to -0.88
NCT01117350978 enrolled · 2010
Δ 2.54-3.88 to 8.93

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.

NCT00518882 phase3completed

Effect of Liraglutide or Exenatide Added to a Background Treatment of Metformin, Sulphonylurea or a Combination of Both on Glycaemic Control in Subjects With Type 2 Diabetes

Ran2007Enrolled467Registered outcomes55Posted comparisons85ConditionsDiabetes, Diabetes Mellitus, Type 2Armsexenatide, liraglutide
PMID 21883806PMID 23010561PMID 22055210PMID 26936426PMID 22193143PMID 22018679PMID 19491536PMID 25504028PMID 23186975PMID 21450987PMID 19245711PMID 21388442other papers from this trial
Open the trial in the graph
NCT03421119 phase3unknown statusstarted 2019, after this paper: background citation

A Phase III, Randomized, Parallel, Double-blind, and Non-inferiority Clinical Trial to Compare Efficacy and Safety of CinnaGen-liraglutide to Innovator Liraglutide Product (Victoza®) in Patients With Type II Diabetes (T2D)

Ran2019Enrolled300Registered outcomes12Posted comparisons0ConditionsDiabetes Mellitus, Type 2ArmsLiraglutide 6 MG/ML Pen Injector, Metformin, Sulfonylurea/non-sulfonylurea insulin secretagogues
PMID 18931095PMID 19289857PMID 19688338PMID 19317822other papers from this trial
Open the trial in the graph
5 · Its place in the literature

Who cites it

536 citing papers in PubMed, 15 syntheses or guidelines pooled it, 1,482 citations in OpenAlex.

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

6 · The record

Corrections and comments

7 · Who and what money

Authors and funding

9 authors at 8 institutions in 5 countries.

John B BuseDivision of Endocrinology, University of North Carolina School of Medicine, Chapel Hill, NC, USA. jbuse@med.unc.edu
Julio Rosenstock
Giorgio Sesti
Wolfgang E Schmidt
Eduard Montanya
Jason H Brett
Marcin Zychma
Lawrence Blonde
LEAD-6 Study Group
Dallas Diabetes Research Center · USInstitut d'Investigació Biomédica de Bellvitge · ESMagna Graecia University · ITNovo Nordisk (Denmark) · DKNovo Nordisk (United States) · USOchsner Medical Center · USSt. Josef-Hospital · DEUniversity of North Carolina Health Care · US

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.

backgroundUnlike most antihyperglycaemic drugs, glucagon-like peptide-1 (GLP-1) receptor agonists have a glucose-dependent action and promote weight loss. We compared the efficacy and safety of liraglutide, a human GLP-1 analogue, with exenatide, an exendin-based GLP-1 receptor agonist.

methodsAdults with inadequately controlled type 2 diabetes on maximally tolerated doses of metformin, sulphonylurea, or both, were stratified by previous oral antidiabetic therapy and randomly assigned to receive additional liraglutide 1.8 mg once a day (n=233) or exenatide 10 microg twice a day (n=231) in a 26-week open-label, parallel-group, multinational (15 countries) study. The primary outcome was change in glycosylated haemoglobin (HbA(1c)). Efficacy analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00518882.

findingsMean baseline HbA(1c) for the study population was 8.2%. Liraglutide reduced mean HbA(1c) significantly more than did exenatide (-1.12% [SE 0.08] vs -0.79% [0.08]; estimated treatment difference -0.33; 95% CI -0.47 to -0.18; p<0.0001) and more patients achieved a HbA(1c) value of less than 7% (54%vs 43%, respectively; odds ratio 2.02; 95% CI 1.31 to 3.11; p=0.0015). Liraglutide reduced mean fasting plasma glucose more than did exenatide (-1.61 mmol/L [SE 0.20] vs -0.60 mmol/L [0.20]; estimated treatment difference -1.01 mmol/L; 95% CI -1.37 to -0.65; p<0.0001) but postprandial glucose control was less effective after breakfast and dinner. Both drugs promoted similar weight losses (liraglutide -3.24 kg vs exenatide -2.87 kg). Both drugs were well tolerated, but nausea was less persistent (estimated treatment rate ratio 0.448, p<0.0001) and minor hypoglycaemia less frequent with liraglutide than with exenatide (1.93 vs 2.60 events per patient per year; rate ratio 0.55; 95% CI 0.34 to 0.88; p=0.0131; 25.5%vs 33.6% had minor hypoglycaemia). Two patients taking both exenatide and a sulphonylurea had a major hypoglycaemic episode.

interpretationLiraglutide once a day provided significantly greater improvements in glycaemic control than did exenatide twice a day, and was generally better tolerated. The results suggest that liraglutide might be a treatment option for type 2 diabetes, especially when weight loss and risk of hypoglycaemia are major considerations.

fundingNovo Nordisk A/S.

Indexed as

Analysis of VarianceBlood GlucoseDiabetes Mellitus, Type 2Dose-Response Relationship, DrugDrug Administration ScheduleExenatideFemaleGlucagon-Like Peptide 1Glycated HemoglobinHumansHypoglycemiaHypoglycemic AgentsInjections, SubcutaneousLinear ModelsLiraglutideLogistic ModelsBlood GlucoseExenatideGlucagon-Like Peptide 1Glycated HemoglobinHypoglycemic AgentsLiraglutidePeptidesVenoms

Identifiers

PMID19515413
OpenAlexW2170606300

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.