Trial reportDiabetes care2009

Efficacy and safety of the human glucagon-like peptide-1 analog liraglutide in combination with metformin and thiazolidinedione in patients with type 2 diabetes (LEAD-4 Met+TZD).

Bernard Zinman, John Gerich, John B Buse, Andrew Lewin, Sherwyn Schwartz, Philip Raskin, Paula M Hale, Milan Zdravkovic, Lawrence Blonde, LEAD-4 Study Investigators

Erratum issued 3 registry-linked trialsOpen access · hybridAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Diabetes care, 2009. The graph read 2 numbers from its abstract, feeding 2 cells of the map, but none could be read as for or against, so it casts no vote. An erratum has been issued. It reports registered trial NCT00333151. Cited by 292 papers, 23 of them syntheses that pooled it.

2numbers the graph read from it
0cells of the map it votes in
292citing papers in PubMed, 23 pooled it
71.4field-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

Systolic blood pressureliraglutide 1.2 mg vs placebono interval or p-value · hypertension, t2dfeeds one cell of the map
Δ -5.60
Systolic blood pressure decreased by 6.7, 5.6, and 1.1 mmHg with 1.2 and 1.8 mg liraglutide and placebo, respectively.
A1C valuesliraglutide (1.2 or 1.8 mg) vs placebono interval or p-value · hypertension, t2dfeeds one cell of the map
Δ -1.00
RESULTS: Mean A1C values decreased significantly more in the liraglutide groups versus placebo (mean +/- SE -1.5 +/- 0.1% for both 1.2 and 1.8 mg liraglutide and -0.5 +/- 0.1% for placebo).

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×blood pressure

No readable resultOpen 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 itNot a counted family in this claim, so removing it changes nothing.
← 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
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

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

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 →
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
NCT039879191,879 enrolled · 2019
Δ -0.51-0.64 to -0.38
NCT026078651,864 enrolled · 2016
Δ -0.50-0.60 to -0.40
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
NCT020581471,170 enrolled · 2014
Δ -0.29-0.38 to -0.19
NCT003184611,091 enrolled · 2006
Δ -1.09-1.30 to -0.88
NCT021289321,089 enrolled · 2014
Δ -0.81-0.96 to -0.67

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.

NCT00333151 phase3completed

Effect on Glycemic Control of Liraglutide in Combination With Rosiglitazone Plus Metformin Versus Rosiglitazone Plus Metformin in Subjects With Type 2 Diabetes

Ran2006Enrolled576Registered outcomes4Posted comparisons0ConditionsDiabetes, Diabetes Mellitus, Type 2Armsliraglutide, Metformin, Rosiglitazone
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
Open the trial in the graph
NCT02930265 naunknown statusnot on this mapstarted 2016, after this paper: background citation

Chinese People's Liberation Army General Hospital

TypeinterventionalSponsorChinese PLA General HospitalRan2016 to 2018Enrolled400ConditionsIschemic CardiomyopathyArmsLiraglutide
5 · Its place in the literature

Who cites it

292 citing papers in PubMed, 23 syntheses or guidelines pooled it, 837 citations in OpenAlex.

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  6. 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
  7. Pooled it
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  12. Pediatric Obesity-Assessment, Treatment, and Prevention: An Endocrine Society Clinical Practice Guideline.The Journal of clinical endocrinology and metabolism · 2017 · on this map
    Guideline
  13. Pooled it
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232 more citing papers are in PubMed but not listed here.

6 · The record

Corrections and comments

  • Erratum issued
7 · Who and what money

Authors and funding

10 authors at 6 institutions in 3 countries.

Bernard ZinmanSamuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada, zinman@lunenfeld.ca
John Gerich
John B Buse
Andrew Lewin
Sherwyn Schwartz
Philip Raskin
Paula M Hale
Milan Zdravkovic
Lawrence Blonde
LEAD-4 Study Investigators
Novo Nordisk (Denmark) · DKDiabetes & Glandular Disease Clinic · USMount Sinai Hospital · CANational Research Institute · USUniversity of North Carolina at Chapel Hill · USUniversity of Rochester · 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.

objectiveTo determine the efficacy and safety of liraglutide (a glucagon-like peptide-1 receptor agonist) when added to metformin and rosiglitazone in type 2 diabetes. RESEARCH DESIGN AND

methodsThis 26-week, double-blind, placebo-controlled, parallel-group trial randomized 533 subjects (1:1:1) to once-daily liraglutide (1.2 or 1.8 mg) or liraglutide placebo in combination with metformin (1 g twice daily) and rosiglitazone (4 mg twice daily). Subjects had type 2 diabetes, A1C 7-11% (previous oral antidiabetes drug [OAD] monotherapy >or=3 months) or 7-10% (previous OAD combination therapy >or=3 months), and BMI <or=45 kg/m(2).

resultsMean A1C values decreased significantly more in the liraglutide groups versus placebo (mean +/- SE -1.5 +/- 0.1% for both 1.2 and 1.8 mg liraglutide and -0.5 +/- 0.1% for placebo). Fasting plasma glucose decreased by 40, 44, and 8 mg/dl for 1.2 and 1.8 mg and placebo, respectively, and 90-min postprandial glucose decreased by 47, 49, and 14 mg/dl, respectively (P < 0.001 for all liraglutide groups vs. placebo). Dose-dependent weight loss occurred with 1.2 and 1.8 mg liraglutide (1.0 +/- 0.3 and 2.0 +/- 0.3 kg, respectively) (P < 0.0001) compared with weight gain with placebo (0.6 +/- 0.3 kg). Systolic blood pressure decreased by 6.7, 5.6, and 1.1 mmHg with 1.2 and 1.8 mg liraglutide and placebo, respectively. Significant increases in C-peptide and homeostasis model assessment of beta-cell function and significant decreases in the proinsulin-to-insulin ratio occurred with liraglutide versus placebo. Minor hypoglycemia occurred more frequently with liraglutide, but there was no major hypoglycemia. Gastrointestinal adverse events were more common with liraglutide, but most occurred early and were transient.

conclusionsLiraglutide combined with metformin and a thiazolidinedione is a well-tolerated combination therapy for type 2 diabetes, providing significant improvements in glycemic control.

Indexed as

AdolescentAdultAgedBlood GlucoseBlood PressureDiabetes Mellitus, Type 2Double-Blind MethodDrug Therapy, CombinationFastingGlucagon-Like Peptide 1Glycated HemoglobinHumansHypoglycemic AgentsLiraglutideMetforminMiddle AgedBlood GlucoseGlucagon-Like Peptide 1Glycated HemoglobinHypoglycemic AgentsLiraglutideMetforminPlacebosThiazolidinediones

Identifiers

PMID19289857
PMCPMC2699702
OpenAlexW2160001758

What Socratic holds

Texttitle and abstract
LicenceCC BY-NC-ND
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.