Evidence map›GLP-1 receptor agonists × glycemic control›PMID 26934259›Full record

Trial reportJAMA2016

Effect of Insulin Glargine Up-titration vs Insulin Degludec/Liraglutide on Glycated Hemoglobin Levels in Patients With Uncontrolled Type 2 Diabetes: The DUAL V Randomized Clinical Trial.

Ildiko Lingvay, Federico Pérez Manghi, Pedro García-Hernández, Paul Norwood, Lucine Lehmann, Mads Jeppe Tarp-Johansen, John B Buse, DUAL V Investigators

Erratum issued Registry-linked trialAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in JAMA, 2016. The graph read 2 numbers from its abstract, feeding 4 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 NCT01952145. Cited by 117 papers, 13 of them syntheses that pooled it.

2numbers the graph read from it
0cells of the map it votes in
117citing papers in PubMed, 13 pooled it
27.7field-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 · t2d, obesityfeeds 2 cells of the map
Δ -0.59-0.74 to -0.45P < .001
HbA1c level reduction was greater with degludec/liraglutide vs glargine (-1.81% for the degludec/liraglutide group vs -1.13% for the glargine group; estimated treatment difference [ETD], -0.59% [95% CI, -0.74% to -0.45%]), meeting criteria for noninferiority (P < .001), and also meeting criteria for statistical superiority (P < .001).
FeedsGLP-1 receptor agonists×glycemic controlInsulin×glycemic control
Hypoglycaemiacomparator not stated · t2d, obesityfeeds 2 cells of the map
IRR 0.430.30 to 0.61P < .001
Treatment with degludec/liraglutide was also associated with weight loss compared with weight gain with glargine (-1.4 kg for degludec/liraglutide vs 1.8 kg for glargine; ETD, -3.20 kg [95% CI, -3.77 to -2.64],P < .001) and fewer confirmed hypoglycemic episodes (episodes/patient-year exposure, 2.23 for degludec/liraglutide vs 5.05 for glargine; estimated rate ratio, 0.43 [95% CI, 0.30 to 0.61],P < .001).
FeedsGLP-1 receptor agonists×hypoglycaemiaInsulin×hypoglycaemia

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: 89 favour the treatment, 16 find no difference, 10 favour the comparator.

Belief with this paper
0.90replicated · 63 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
This paper’s trial, registry resultNCT01952145 · 557 enrolled · 2013
Treatment contrast -0.59-0.74 to -0.45
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

GLP-1 receptor agonists×hypoglycaemia

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

10 readable studies in this cell: 2 favour the treatment, 2 find no difference, 6 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 →
1 · no effect
NCT018365231,398 enrolled · 2013
IRR 1.311.07 to 1.59
NCT02607306819 enrolled · 2015
Treatment contrast 0.480.35 to 0.68
NCT00393718400 enrolled · 2006
IRR 0.200.12 to 0.35
NCT02152371300 enrolled · 2014
OR 4.172.32 to 7.47
NCT04591626291 enrolled · 2020
OR 4.582.64 to 7.95
NCT05564039282 enrolled · 2022
OR 20.48.40 to 49.8
NCT01620489279 enrolled · 2012
OR 3.942.12 to 7.30

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

Insulin×glycemic control

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

40 readable studies in this cell: 13 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.

Insulin×hypoglycaemia

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

4 readable studies in this cell: 2 favour the treatment, 1 find no difference, 1 favour the comparator.

Belief with this paper
0.00contested · 0 families support, 3 contradict · head-to-head
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the comparatorfavours the treatment →
1 · no effect
NCT045379231,428 enrolled · 2020
OR 8.195.66 to 11.8
NCT02551874650 enrolled · 2015
OR 0.400.30 to 0.62

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.

NCT01952145 phase3completed

A Trial Comparing the Efficacy and Safety of Insulin Degludec/Liraglutide Versus Insulin Glargine in Subjects With Type 2 Diabetes Mellitus (DUAL™ V - Basal Insulin Switch)

Ran2013Enrolled557Registered outcomes3Posted comparisons1ConditionsDiabetes, Diabetes Mellitus, Type 2Armsinsulin degludec/liraglutide, Insulin glargine
PMID 30383495PMID 28294641PMID 28281218PMID 28643425PMID 28417535PMID 29276398other papers from this trial
Open the trial in the graph
5 · Its place in the literature

Who cites it

117 citing papers in PubMed, 13 syntheses or guidelines pooled it, 213 citations in OpenAlex.

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

6 · The record

Corrections and comments

7 · Who and what money

Authors and funding

8 authors at 5 institutions in 4 countries.

Ildiko LingvayDepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas2Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas.
Federico Pérez ManghiCentro de Investigaciones Metabolicas, Buenos Aires, Argentina.
Pedro García-HernándezServicio de Endocrinologia, Hospital Universitario de Monterrey "Dr José Eleuterio-González," Nuevo León, México.
Paul NorwoodValley Research, Fresno, California.
Lucine LehmannNovo Nordisk A/S, Søborg, Denmark.
Mads Jeppe Tarp-JohansenNovo Nordisk A/S, Søborg, Denmark.
John B BuseUniversity of North Carolina School of Medicine, Chapel Hill.
DUAL V Investigators
Novo Nordisk (Denmark) · DKCentro de Investigaciones Cardiovasculares · ARHospital Universitario Dr José Eleuterio Gonzalez · MXThe University of Texas Southwestern Medical Center · USUniversity of North Carolina at Chapel Hill · 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.

importanceAchieving glycemic control remains a challenge for patients with type 2 diabetes, even with insulin therapy.

objectiveTo assess whether a fixed ratio of insulin degludec/liraglutide was noninferior to continued titration of insulin glargine in patients with uncontrolled type 2 diabetes treated with insulin glargine and metformin. DESIGN, SETTING, AND

participantsPhase 3, multinational, multicenter, 26-week, randomized, open-label, 2-group, treat-to-target trial conducted at 75 centers in 10 countries from September 2013 to November 2014 among 557 patients with uncontrolled diabetes treated with glargine (20-50 U) and metformin (≥1500 mg/d) with glycated hemoglobin (HbA1c) levels of 7% to 10% and a body mass index of 40 or lower.

interventions1:1 randomization to degludec/liraglutide (n = 278; maximum dose, 50 U of degludec/1.8 mg of liraglutide) or glargine (n = 279; no maximum dose), with twice-weekly titration to a glucose target of 72 to 90 mg/dL. MAIN OUTCOMES AND MEASURES: Primary outcome measure was change in HbA1c level after 26 weeks, with a noninferiority margin of 0.3% (upper bound of 95% CI, <0.3%). If noninferiority of degludec/liraglutide was achieved, secondary end points were tested for statistical superiority and included change in HbA1c level, change in body weight, and rate of confirmed hypoglycemic episodes.

resultsAmong 557 randomized patients (mean: age, 58.8 years; women, 49.7%), 92.5% of patients completed the trial and provided data at 26 weeks. Baseline HbA1c level was 8.4% for the degludec/liraglutide group and 8.2% for the glargine group. HbA1c level reduction was greater with degludec/liraglutide vs glargine (-1.81% for the degludec/liraglutide group vs -1.13% for the glargine group; estimated treatment difference [ETD], -0.59% [95% CI, -0.74% to -0.45%]), meeting criteria for noninferiority (P < .001), and also meeting criteria for statistical superiority (P < .001). Treatment with degludec/liraglutide was also associated with weight loss compared with weight gain with glargine (-1.4 kg for degludec/liraglutide vs 1.8 kg for glargine; ETD, -3.20 kg [95% CI, -3.77 to -2.64],P < .001) and fewer confirmed hypoglycemic episodes (episodes/patient-year exposure, 2.23 for degludec/liraglutide vs 5.05 for glargine; estimated rate ratio, 0.43 [95% CI, 0.30 to 0.61],P < .001). Overall and serious adverse event rates were similar in the 2 groups, except for more nonserious gastrointestinal adverse events reported with degludec/liraglutide (adverse events, 79 for degludec/liraglutide vs 18 for glargine). CONCLUSIONS AND RELEVANCE: Among patients with uncontrolled type 2 diabetes taking glargine and metformin, treatment with degludec/liraglutide compared with up-titration of glargine resulted in noninferior HbA1c levels, with secondary analyses indicating greater HbA1c level reduction after 26 weeks of treatment. Further studies are needed to assess longer-term efficacy and safety.

trial registrationclinicaltrials.gov Identifier: NCT01952145.

Indexed as

Diabetes Mellitus, Type 2FemaleGlycated HemoglobinHumansHypoglycemiaHypoglycemic AgentsInsulin GlargineInsulin, Long-ActingMaleMetforminMiddle AgedWeight GainWeight LossGlycated HemoglobinHypoglycemic Agentsinsulin degludecInsulin GlargineInsulin, Long-ActingMetformin

Identifiers

PMID26934259
OpenAlexW2292172438

What OpenQuestion holds

Texttitle and abstract
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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 OpenQuestion graph.