Evidence map›Insulin × glycemic control›PMID 31407845›Full record

Trial reportDiabetes, obesity & metabolism2019

Superior efficacy with a fixed-ratio combination of insulin degludec and liraglutide (IDegLira) compared with insulin degludec and liraglutide in insulin-naïve Japanese patients with type 2 diabetes in a phase 3, open-label, randomized trial.

Kohei Kaku, Eiichi Araki, Yukio Tanizawa, Bue Ross Agner, Tomoyuki Nishida, Mattis Ranthe, Nobuya Inagaki

Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase IIIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Diabetes, obesity & metabolism, 2019. The graph read 4 numbers from its abstract, feeding 2 cells of the map: it . It reports registered trial NCT02607306. Cited by 18 papers, 5 of them syntheses that pooled it.

4numbers the graph read from it
2cells of the map it votes in
18citing papers in PubMed, 5 pooled it
1.8field-weighted citation impact, top 14% 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 →
0.250.524101 · no effect
Rates of severe or blood glucose-confirmed hypoglycaemiaIDegLira vs liraglutidefavours the comparator · t2dfeeds one cell of the map
IRR 37.619.8 to 71.3P < .0001
Rates of severe or blood glucose-confirmed hypoglycaemia for IDegLira were lower versus degludec (rate ratio 0.48 [95% CI 0.35; 0.68]; P < .0001), but higher versus liraglutide (rate ratio 37.58 [95% CI 19.80; 71.31]; P < .0001).
FeedsInsulin×glycemic control
Rates of severe or blood glucose-confirmed hypoglycaemiaIDegLira vs degludecfavours the treatment · t2dfeeds one cell of the map
IRR 0.480.35 to 0.68P < .0001
Rates of severe or blood glucose-confirmed hypoglycaemia for IDegLira were lower versus degludec (rate ratio 0.48 [95% CI 0.35; 0.68]; P < .0001), but higher versus liraglutide (rate ratio 37.58 [95% CI 19.80; 71.31]; P < .0001).
FeedsInsulin×glycemic control

Differences

← favours the treatmentfavours the comparator →
-8.180 · no effect
Glycated haemoglobin (HbA1c)IDegLira vs degludecfavours the treatment · t2dfeeds one cell of the map
Δ -6.91-8.18 to -5.64
RESULTS: After 52 weeks, glycated haemoglobin (HbA1c) decreased by 26 mmol/mol with IDegLira vs 20 mmol/mol with degludec and liraglutide: estimated treatment differences were -6.91 mmol/mol (95% confidence interval [CI] -8.18; -5.64) and -5.30 mmol/mol (95% CI -6.58; -4.03), confirming non-inferiority of IDegLira to degludec and superiority of IDegLira to liraglutide (P < .0001 for both [primary endpoint]).
FeedsInsulin×adverse events & safety
Glycated haemoglobin (HbA1c)IDegLira vs liraglutidefavours the treatment · t2dfeeds one cell of the map
Δ -5.30-6.58 to -4.03< .0001
RESULTS: After 52 weeks, glycated haemoglobin (HbA1c) decreased by 26 mmol/mol with IDegLira vs 20 mmol/mol with degludec and liraglutide: estimated treatment differences were -6.91 mmol/mol (95% confidence interval [CI] -8.18; -5.64) and -5.30 mmol/mol (95% CI -6.58; -4.03), confirming non-inferiority of IDegLira to degludec and superiority of IDegLira to liraglutide (P < .0001 for both [primary endpoint]).
FeedsInsulin×adverse events & safety

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 it
0.50This paper does not move the number.
← favours the treatmentfavours the comparator →
0 · no effect
This paper’s trial, registry resultNCT02607306 · 819 enrolled · 2015
Treatment contrast -0.48-0.60 to -0.37
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

Insulin×adverse events & safety

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

17 readable studies in this cell: 8 favour the treatment, 5 find no difference, 4 favour the comparator.

Belief with this paper
0.09contested · 1 family supports, 8 contradict · against placebo
Without it
0.10This paper moves it by −0.01.
← favours the treatmentfavours the comparator →
0 · no effect
This paper’s trial, registry resultNCT02607306 · 819 enrolled · 2015
Treatment contrast -0.48-0.60 to -0.37
This paper · 2019
Δ -6.91-8.18 to -5.64
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
NCT032680051,264 enrolled · 2017
Δ -0.04-0.11 to 0.03
NCT009606611,036 enrolled · 2009
Δ -0.04-0.18 to 0.11
NCT01117350978 enrolled · 2010
Δ 2.54-3.88 to 8.93
NCT01075282810 enrolled · 2010
Δ -0.45-0.60 to -0.29
NCT01648582774 enrolled · 2012
Δ -0.57-0.74 to -0.40
NCT05259033683 enrolled · 2022
Δ -0.44-0.56 to -0.33
NCT01123980521 enrolled · 2010
Δ -0.12-0.25 to 0.02
NCT02787551514 enrolled · 2016
Δ -0.64-0.77 to -0.51
NCT01676116438 enrolled · 2012
Treatment contrast -0.94-1.11 to -0.78
NCT01618162435 enrolled · 2012
Δ -1.02-1.18 to -0.87
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.

NCT02607306 phase3completed

A Trial Comparing the Efficacy and Safety of Insulin Degludec/Liraglutide, Insulin Degludec and Liraglutide in Japanese Subjects With Type 2 Diabetes Mellitus

Ran2015Enrolled819Registered outcomes40Posted comparisons5ConditionsDiabetes, Diabetes Mellitus, Type 2Armsinsulin degludec, insulin degludec/liraglutide, liraglutide
PMID 33595901other papers from this trial
Open the trial in the graph
5 · Its place in the literature

Who cites it

18 citing papers in PubMed, 5 syntheses or guidelines pooled it, 24 citations in OpenAlex.

  1. 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

7 authors at 5 institutions in 2 countries.

Kohei KakuDepartment of Internal Medicine, Kawasaki Medical School, Kurashiki, Japan.ORCID 0000-0003-1574-0565
Eiichi ArakiDepartment of Metabolic Medicine, Kumamoto University, Kumamoto, Japan.
Yukio TanizawaGraduate School of Medicine, Yamaguchi University, Ube, Japan.
Bue Ross AgnerNovo Nordisk A/S, Søborg, Denmark.
Tomoyuki NishidaNovo Nordisk Pharma Ltd, Tokyo, Japan.
Mattis RantheNovo Nordisk A/S, Søborg, Denmark.
Nobuya InagakiDepartment of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Novo Nordisk (Denmark) · DKKawasaki Medical School · JPKumamoto University · JPKyoto University · JPYamaguchi University · JP

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.

aimsTo investigate the efficacy and safety of insulin degludec/liraglutide (IDegLira) compared with its individual components in Japanese people with type 2 diabetes (T2D) uncontrolled on an oral antidiabetic drug (OAD). MATERIALS AND

methodsThis 52-week, open-label, multicentre, treat-to-target trial randomized participants (n = 819) 1:1:1 to IDegLira, liraglutide 1.8 mg or degludec, as add-on to their pre-trial OAD. The maximum IDegLira dose was 50 dose steps (50 U degludec/1.8 mg liraglutide), there was no maximum dose for degludec, and both were titrated based on individual blood glucose measurements.

resultsAfter 52 weeks, glycated haemoglobin (HbA1c) decreased by 26 mmol/mol with IDegLira vs 20 mmol/mol with degludec and liraglutide: estimated treatment differences were -6.91 mmol/mol (95% confidence interval [CI] -8.18; -5.64) and -5.30 mmol/mol (95% CI -6.58; -4.03), confirming non-inferiority of IDegLira to degludec and superiority of IDegLira to liraglutide (P < .0001 for both [primary endpoint]). Mean body weight changes were 2.9 kg, 4.1 kg and -1.0 kg with IDegLira, degludec and liraglutide, respectively, showing superiority of IDegLira versus degludec (P = .0001), but a significant difference in favour of liraglutide (P < .0001). Rates of severe or blood glucose-confirmed hypoglycaemia for IDegLira were lower versus degludec (rate ratio 0.48 [95% CI 0.35; 0.68]; P < .0001), but higher versus liraglutide (rate ratio 37.58 [95% CI 19.80; 71.31]; P < .0001). Mean daily total insulin dose was lower with IDegLira (27.7 U) versus degludec (34.8 U; P < .0001). Overall adverse event (AE) rates were similar. In total, 34.9%, 22.9% and 41.8% of IDegLira-, degludec- and liraglutide-treated participants experienced gastrointestinal AEs.

conclusionIDegLira was superior to degludec and liraglutide in terms of HbA1c reduction and superior to degludec in terms of body weight change and rates of hypoglycaemia in Japanese people with T2D.

Indexed as

AdultAgedAged, 80 and overBlood GlucoseDiabetes Mellitus, Type 2Drug CombinationsFemaleGlycated HemoglobinHumansHypoglycemiaHypoglycemic AgentsInsulin, Long-ActingJapanLiraglutideMaleMiddle AgedBlood GlucoseDrug CombinationsGlycated HemoglobinHypoglycemic AgentsIDegLirainsulin degludecInsulin, Long-ActingLiraglutidebasal insulinliraglutide; hypoglycaemiarandomized trialtype 2 diabetes

Identifiers

PMID31407845
PMCPMC6899795
OpenAlexW2970995457

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.