Trial reportDiabetes, obesity & metabolism2019

Superior efficacy of insulin degludec/liraglutide versus insulin glargine U100 as add-on to sodium-glucose co-transporter-2 inhibitor therapy: A randomized clinical trial in people with uncontrolled type 2 diabetes.

Athena Philis-Tsimikas, Liana K Billings, Robert Busch, Cristobal Morales Portillo, Rakesh Sahay, Natalie Halladin, Sarah Eggert, Kamilla Begtrup, Stewart Harris

Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase IIIRandomized Controlled Trial
In one paragraph

Trial report in Diabetes, obesity & metabolism, 2019. The graph read 3 numbers from its abstract, feeding 2 cells of the map, but none could be read as for or against, so it casts no vote. It reports registered trial NCT02773368. Cited by 46 papers, 7 of them syntheses that pooled it.

3numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed, 7 pooled it
6.1field-weighted citation impact, top 3% 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 · t2dfeeds one cell of the map
Δ -3.90-5.45 to -2.35
Mean HbA1c reductions were 21 mmol/mol (1.9%-points) with IDegLira and 18 mmol/mol (1.7%-points) with IGlar U100; confirming non-inferiority (P < 0.0001) and superiority of IDegLira (difference in HbA1c change -3.90 mmol/mol; 95% confidence interval [CI] -5.45; -2.35 (-0.36%-points; 95% CI -0.50, -0.21)).
Glycemic controlcomparator not stated · t2dfeeds one cell of the map
IRR 0.420.23 to 0.75
Superiority for IDegLira over IGlar U100 was also confirmed for: body weight (difference -1.92 kg; 95% CI -2.64, -1.19); severe or blood-glucose-confirmed symptomatic hypoglycaemia (rate ratio 0.42; 95% CI 0.23, 0.75); total daily insulin dose (difference -15.37 U; 95% CI -19.60, -11.13).
Body weight & compositioncomparator not stated · t2dfeeds one cell of the map
Δ -1.92-2.64 to -1.19
Superiority for IDegLira over IGlar U100 was also confirmed for: body weight (difference -1.92 kg; 95% CI -2.64, -1.19); severe or blood-glucose-confirmed symptomatic hypoglycaemia (rate ratio 0.42; 95% CI 0.23, 0.75); total daily insulin dose (difference -15.37 U; 95% CI -19.60, -11.13).

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.

Insulin×body weight & composition

No readable resultOpen 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 itNot a counted family in this claim, so removing it changes nothing.
← favours the comparatorfavours the treatment →
0 · no effect
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

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.

NCT02773368 phase3completed

A Clinical Trial Comparing Glycaemic Control and Safety of Insulin Degludec/Liraglutide (IDegLira) Versus Insulin Glargine (IGlar) as add-on Therapy to SGLT2i in Subjects With Type 2 Diabetes Mellitus. DUALTM IX - Add-on to SGLT2i

Ran2016Enrolled420Registered outcomes33Posted comparisons5ConditionsDiabetes, Diabetes Mellitus, Type 2Armsinsulin degludec/liraglutide, Insulin glargine
Open the trial in the graph
5 · Its place in the literature

Who cites it

46 citing papers in PubMed, 7 syntheses or guidelines pooled it, 65 citations in OpenAlex.

  1. Pooled it
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  7. Exploring the Role of GLP-1 Agents in Managing Diabetic Foot Ulcers: A Narrative and Systematic Review.Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society
    Pooled it
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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

9 authors at 7 institutions in 5 countries.

Athena Philis-TsimikasScripps Whittier Diabetes Institute, San Diego, California.ORCID 0000-0002-3986-9630
Liana K BillingsNorthShore University HealthSystem, Skokie, Illinois.
Robert BuschAlbany Medical Centre, Albany, New York.
Cristobal Morales PortilloHospital Virgen Macarena, Seville, Spain.
Rakesh SahayOsmania Medical College, Hyderabad, India.
Natalie HalladinNovo Nordisk, Søborg, Denmark.
Sarah EggertNovo Nordisk, Søborg, Denmark.
Kamilla BegtrupNovo Nordisk, Søborg, Denmark.
Stewart HarrisWestern University, London, Ontario, Canada.ORCID 0000-0002-1794-6551
Novo Nordisk (Denmark) · DKAlbany Medical Center Hospital · USHospital Universitario Virgen Macarena · ESNorthShore University HealthSystem · USOsmania Medical College · INScripps Whittier Diabetes Institute · USWestern University · CA

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.

aimTo investigate the efficacy and safety of insulin degludec/liraglutide (IDegLira) versus insulin glargine 100 units/mL (IGlar U100) as add-on to sodium-glucose co-transporter-2 (SGLT2) inhibitor therapy. MATERIALS AND

methodsIn this 26-week, phase IIIb, open-label, parallel-group, treat-to-target trial, conducted at 74 sites in 11 countries, insulin-naïve people aged ≥18 years with glycated haemoglobin (HbA1c) 53-97 mmol/mol (7.0-11.0%), body mass index 20-40 kg/m

resultsA total of 210 participants were randomized to each treatment arm. Mean HbA1c reductions were 21 mmol/mol (1.9%-points) with IDegLira and 18 mmol/mol (1.7%-points) with IGlar U100; confirming non-inferiority (P < 0.0001) and superiority of IDegLira (difference in HbA1c change -3.90 mmol/mol; 95% confidence interval [CI] -5.45; -2.35 (-0.36%-points; 95% CI -0.50, -0.21)). Superiority for IDegLira over IGlar U100 was also confirmed for: body weight (difference -1.92 kg; 95% CI -2.64, -1.19); severe or blood-glucose-confirmed symptomatic hypoglycaemia (rate ratio 0.42; 95% CI 0.23, 0.75); total daily insulin dose (difference -15.37 U; 95% CI -19.60, -11.13). The overall treatment-emergent adverse event rate was higher with IDegLira as a result of higher increased lipase and nausea rates.

conclusionsThe favourable safety and efficacy profile of IDegLira in people with uncontrolled T2D on SGLT2 inhibitors, and lower weight gain and hypoglycaemia risk versus IGlar U100, suggest that clinicians should consider IDegLira initiation in this population.

Indexed as

Hypoglycemic AgentsInsulin, Long-ActingLiraglutideSodium-Glucose Transporter 2 InhibitorsAgedDiabetes Mellitus, Type 2Drug-Related Side Effects and Adverse ReactionsFemaleGlycated HemoglobinHumansMaleMiddle AgedGlycated Hemoglobinhemoglobin A1c protein, humanHypoglycemic Agentsinsulin degludecInsulin, Long-ActingLiraglutideSodium-Glucose Transporter 2 InhibitorsGLP-1 analogueinsulin therapyliraglutiderandomized trialSGLT2 inhibitortype 2 diabetes

Identifiers

PMID30761720
PMCPMC6593861
OpenAlexW2911886982

What Socratic holds

Texttitle and abstract
LicenceCC BY-NC
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.