Evidence map›Insulin × body weight & composition›PMID 19688338›Full record

Trial reportDiabetologia2009

Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met+SU): a randomised controlled trial.

D Russell-Jones, A Vaag, O Schmitz, B K Sethi, N Lalic, S Antic, M Zdravkovic, G M Ravn, R Simó, Liraglutide Effect and Action in Diabetes 5 (LEAD-5) met+SU Study Group

2 registry-linked trialsOpen access · hybridAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Diabetologia, 2009. The graph read 3 numbers from its abstract, feeding 3 cells of the map: it supports the treatment in 2, favours the comparator in 1. It reports registered trial NCT00331851. Cited by 302 papers, 25 of them syntheses that pooled it.

3numbers the graph read from it
3cells of the map it votes in
302citing papers in PubMed, 25 pooled it
64.0field-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 →
-2.202.860 · no effect
Body weight & compositionfavours the comparator · against placebo · obesity, t2dfeeds one cell of the map
Δ 2.86p < 0.0001
There was greater weight loss with liraglutide vs placebo (treatment difference -1.39 kg, 95% CI 2.10, 0.69; p = 0.0001), and vs glargine (treatment difference -3.43 kg, 95% CI 4.00, 2.86; p < 0.0001).
FeedsInsulin×body weight & composition
Blood pressurefavours the treatment · against placebo · obesity, t2dfeeds 2 cells of the map
Δ -2.20p = 0.0001
Liraglutide reduced systolic BP (-4.0 mmHg) vs glargine (+0.5 mmHg; -4.5 mmHg difference, 95% CI 6.8, -2.2; p = 0.0001) but not vs placebo (p = 0.0791).
FeedsGLP-1 receptor agonists×blood pressureInsulin×blood pressure
Body weight & compositionfavours the comparator · against placebo · obesity, t2dfeeds one cell of the map
Δ 0.69p = 0.0001
There was greater weight loss with liraglutide vs placebo (treatment difference -1.39 kg, 95% CI 2.10, 0.69; p = 0.0001), and vs glargine (treatment difference -3.43 kg, 95% CI 4.00, 2.86; p < 0.0001).
FeedsInsulin×body weight & composition

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×body weight & composition

ContradictsOpen on the map →What to test next →

12 readable studies in this cell: 1 favour the treatment, 1 find no difference, 10 favour the comparator.

Belief with this paper
0.00contested · 0 families support, 2 contradict · against placebo
Without it
0.00This paper does not move the number.
← favours the treatmentfavours the comparator →
0 · no effect
This paper584 enrolled · 2006
Δ 0.69
NCT037306622,002 enrolled · 2018
Δ -9.00-9.80 to -8.30
NCT038829701,444 enrolled · 2019
Δ -9.80-10.8 to -8.80
NCT045379231,428 enrolled · 2020
Δ -10.7-11.5 to -9.90
NCT020581471,170 enrolled · 2014
Δ 40.633.6 to 47.6
NCT04093752917 enrolled · 2019
Δ -6.50-7.40 to -5.60
NCT01768559894 enrolled · 2013
Δ -1.99-2.59 to -1.40
NCT01075282810 enrolled · 2010
Δ 2.832.33 to 3.33
NCT02551874650 enrolled · 2015
Δ -3.64-4.20 to -3.09
Weight Gain Was Associated With Worsening Glycemia and Cardiovascular …PMID 40267365 · 2025
Δ 0.450.16 to 0.74
Continuing metformin when starting insulin in patients with Type 2 dia…PMID 15842521 · 2005
Δ 1.500.20 to 2.90

GLP-1 receptor agonists×blood pressure

SupportsOpen on the map →What to test next →

10 readable studies in this cell: 4 favour the treatment, 5 find no difference, 1 favour the comparator.

Belief with this paper
0.50contested · 3 families support, 1 contradict · against placebo
Without it
0.50This paper does not move the number.
← favours the treatmentfavours the comparator →
0 · no effect
NCT00676338820 enrolled · 2008
Δ 0.36-1.02 to 1.73
NCT00781937422 enrolled · 2008
Treatment Contrast -2.72-4.69 to -0.76
NCT02492763176 enrolled · 2015
Δ -1.10-6.20 to 4.10
Effects of Semaglutide on Body Composition and GFR: A Prespecified Ana…PMID 42308057 · 125 enrolled · 2022
change -0.90-1.60 to -0.10
NCT04019197108 enrolled · 2019
β coefficient -0.05-0.10 to -0.01
NCT0488111060 enrolled · 2021
Δ -0.00-5.80 to 5.80
Effects of the glucagon-like peptide-1 receptor agonist liraglutide on…PMID 28129251 · 2017
Δ 4.20-0.74 to 9.17
The effects of GLP-1 based therapies on postprandial haemodynamics: Tw…PMID 28086201 · 2017
Δ 684439 to 929
Effect of liraglutide on ambulatory blood pressure in patients with hy…PMID 30242948 · 2019
Δ -1.42-4.25 to 1.40
Heart rate acceleration with GLP-1 receptor agonists in type 2 diabete…PMID 27777261 · 2017
Δ -12.6

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

Insulin×blood pressure

SupportsOpen on the map →What to test next →

No other readable study in this cell yet. This paper is the evidence.

Belief with this paper
0.35one trial · 1 family supports, 0 contradict · against placebo
Without itThis paper is the only evidence family behind the claim. Without it there is no number.
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.

NCT00331851 phase3completed

Liraglutide Effect and Action in Diabetes (LEAD-5): Effect on Glycaemic Control After Once Daily Administration of Liraglutide in Combination With Glimepiride and Metformin Versus Glimepiride and Metformin Combination Therapy, and Versus Insulin Glargine Added to Glimepiride and Metformin Combination Therapy in Subjects With Type 2 Diabetes.A Six-month Randomised, Double-blind, Parallel-group, Multi-centre, Multi-national Trial With an Open-label Treat-to-target Insulin Glargine Control Arm.

Ran2006Enrolled584Registered outcomes5Posted comparisons0ConditionsDiabetes, Diabetes Mellitus, Type 2ArmsGlimepiride, Insulin glargine, liraglutide, Metformin
PMID 21883806PMID 23010561PMID 22055210PMID 22193143PMID 19491536PMID 25323312PMID 25504028PMID 23186975PMID 21450987PMID 19245711PMID 19878259PMID 22862847other 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 19515413PMID 19317822other papers from this trial
Open the trial in the graph
5 · Its place in the literature

Who cites it

302 citing papers in PubMed, 25 syntheses or guidelines pooled it, 827 citations in OpenAlex.

  1. Pooled it
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  7. American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update.Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists · 2022
    Guideline
  8. Guideline
  9. Pooled it
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242 more citing papers are in PubMed but not listed here.

6 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

7 · Who and what money

Authors and funding

10 authors at 8 institutions in 5 countries.

D Russell-JonesDepartment of Diabetes and Endocrinology, Royal Guildford Hospital, UK. drj@royalsurrey.nhs.uk
A Vaag
O Schmitz
B K Sethi
N Lalic
S Antic
M Zdravkovic
G M Ravn
R Simó
Liraglutide Effect and Action in Diabetes 5 (LEAD-5) met+SU Study Group
Novo Nordisk (Denmark) · DKAarhus University Hospital · DKCARE Hospitals · INGuildford Hospital · GBSteno Diabetes Centers · DKUniversity of Belgrade · RSUniversity of Nis · RSVall d'Hebron Institut de Recerca · ES

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.

aims/hypothesisThe aim of the study was to compare the efficacy and safety of liraglutide in type 2 diabetes mellitus vs placebo and insulin glargine (A21Gly,B31Arg,B32Arg human insulin), all in combination with metformin and glimepiride.

methodsThis randomised (using a telephone or web-based randomisation system), parallel-group, controlled 26 week trial of 581 patients with type 2 diabetes mellitus on prior monotherapy (HbA(1c) 7.5-10%) and combination therapy (7.0-10%) was conducted in 107 centres in 17 countries. The primary endpoint was HbA(1c). Patients were randomised (2:1:2) to liraglutide 1.8 mg once daily (n = 232), liraglutide placebo (n = 115) and open-label insulin glargine (n = 234), all in combination with metformin (1 g twice daily) and glimepiride (4 mg once daily). Investigators, participants and study monitors were blinded to the treatment status of the liraglutide and placebo groups at all times.

resultsThe number of patients analysed as intention to treat were: liraglutide n = 230, placebo n = 114, insulin glargine n = 232. Liraglutide reduced HbA(1c) significantly vs glargine (1.33% vs 1.09%; -0.24% difference, 95% CI 0.08, 0.39; p = 0.0015) and placebo (-1.09% difference, 95% CI 0.90, 1.28; p < 0.0001). There was greater weight loss with liraglutide vs placebo (treatment difference -1.39 kg, 95% CI 2.10, 0.69; p = 0.0001), and vs glargine (treatment difference -3.43 kg, 95% CI 4.00, 2.86; p < 0.0001). Liraglutide reduced systolic BP (-4.0 mmHg) vs glargine (+0.5 mmHg; -4.5 mmHg difference, 95% CI 6.8, -2.2; p = 0.0001) but not vs placebo (p = 0.0791). Rates of hypoglycaemic episodes (major, minor and symptoms only, respectively) were 0.06, 1.2 and 1.0 events/patient/year, respectively, in the liraglutide group (vs 0, 1.3, 1.8 and 0, 1.0, 0.5 with glargine and placebo, respectively). A slightly higher number of adverse events (including nausea at 14%) were reported with liraglutide, but only 9.8% of participants in the group receiving liraglutide developed anti-liraglutide antibodies. CONCLUSIONS/

interpretationLiraglutide added to metformin and sulfonylurea produced significant improvement in glycaemic control and bodyweight compared with placebo and insulin glargine. The difference vs insulin glargine in HbA(1c) was within the predefined non-inferiority margin.

trial registrationClinicalTrials.gov NCT00331851.

fundingThe study was funded by Novo Nordisk A/S.

Indexed as

AdolescentAdultAgedAged, 80 and overBlood GlucoseBody WeightDiabetes Mellitus, Type 2Drug Therapy, CombinationFemaleGlucagon-Like Peptide 1HumansHypoglycemic AgentsInsulinInsulin GlargineInsulin, Long-ActingLiraglutideBlood GlucoseGlucagon-Like Peptide 1Hypoglycemic AgentsInsulinInsulin GlargineInsulin, Long-ActingLiraglutideMetforminPlacebosSulfonylurea Compounds

Identifiers

PMID19688338
PMCPMC2744824
OpenAlexW2137352234

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.