Trial reportDiabetes care2014

Advancing basal insulin replacement in type 2 diabetes inadequately controlled with insulin glargine plus oral agents: a comparison of adding albiglutide, a weekly GLP-1 receptor agonist, versus thrice-daily prandial insulin lispro.

Julio Rosenstock, Vivian A Fonseca, Jorge L Gross, Robert E Ratner, Bo Ahrén, Francis C C Chow, Fred Yang, Diane Miller, Susan L Johnson, Murray W Stewart and 2 more

2 registry-linked trialsAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in Diabetes care, 2014. The graph read 1 number from its abstract, feeding 2 cells of the map, but none could be read as for or against, so it casts no vote. It is linked to 2 registered trials, which are not on this map. Cited by 84 papers, 6 of them syntheses that pooled it.

1number the graph read from it
0cells of the map it votes in
84citing papers in PubMed, 6 pooled it
26.4field-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

Glycemic controlcomparator not stated · t2dfeeds 2 cells of the map
Δ -0.16-0.32 to 0.00P < 0.0001
RESULTS: At week 26, HbA1c decreased from baseline by -0.82 ± SE 0.06% (9.0 mmol/mol) with albiglutide and -0.66 ± 0.06% (7.2 mmol/mol) with lispro; treatment difference, -0.16% (95% CI -0.32 to 0.00; 1.8 mmol/mol; P < 0.0001), meeting the noninferiority end point (margin, 0.4%).

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: 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.

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.

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.

NCT03819790 phase4completedstarted 2018, after this paper: background citation

Variability of Glucose Assessed in a Randomized Trial Comparing the Initiation of A Treatment Approach With Biosimilar Basal Insulin Analog Or a Titratable iGlarLixi combinatioN in Type 2 Diabetes Among South Asian Subjects (VARIATION 2 SA Trial)

Ran2018Enrolled119Registered outcomes30Posted comparisons0ConditionsDiabetes Mellitus, Type 2ArmsBasal insulin Basaglar/Lantus + gliclazide MR, Basal insulin glargine and lixisenatide, Metformin
Open the trial in the graph
NCT03199638 nacompletednot on this mapstarted 2016, after this paper: background citation

Exercise Snacks and Glutamine to Improve Glucose Control in Adolescents With Type 1 Diabetes

TypeinterventionalSponsorNemours Children's ClinicRan2016 to 2017Enrolled14ConditionsDiabetes Mellitus, Type 1, Autoimmune Diseases, Diabetes Mellitus, Endocrine System DiseasesArmsGlutamine vs. Placebo, Exercise
5 · Its place in the literature

Who cites it

84 citing papers in PubMed, 6 syntheses or guidelines pooled it, 202 citations in OpenAlex.

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

6 · The record

Corrections and comments

7 · Who and what money

Authors and funding

12 authors at 10 institutions in 6 countries.

Julio RosenstockDallas Diabetes and Endocrine Center, Medical City Dallas Hospital, Dallas, TX juliorosenstock@dallasdiabetes.com.
Vivian A FonsecaTulane University Health Sciences Center, New Orleans, LA.
Jorge L GrossEndocrine Division, Hospital de Clínicas de Porto Alegre and Universidade Federal do Sul, Porto Alegre, Brazil.
Robert E RatnerMedstar Health Research Institute, Hyattsville, MD.
Bo AhrénDepartment of Medicine, Lund University, Lund, Sweden.
Francis C C ChowThe Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.
Fred YangGlaxoSmithKline, Upper Merion, PA.
Diane MillerGlaxoSmithKline, Upper Merion, PA.
Susan L JohnsonGlaxoSmithKline, Research Triangle Park, NC.
Murray W StewartGlaxoSmithKline, Upper Merion, PA.
Lawrence A LeiterKeenan Research Center, Li Ka Shing Knowledge Institute, St. Michael's Hospital, and Division of Endocrinology and Metabolism, University of Toronto, Toronto, Ontario, Canada.
Harmony 6 Study Group
GlaxoSmithKline (United States) · USChinese University of Hong Kong · CNGlaxoSmithKline (United Kingdom) · GBHospital de Clínicas de Porto Alegre · BRLund University · SEMedical City Dallas Hospital · USMedStar Health · USResearch Triangle Park Foundation · USTulane University · USUniversity of Toronto · 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.

objectiveGLP-1 receptor agonists may provide an alternative to prandial insulin for advancing basal insulin therapy. Harmony 6 was a randomized, open-label, active-controlled trial testing once-weekly albiglutide vs. thrice-daily prandial insulin lispro as an add-on to titrated once-daily insulin glargine. RESEARCH DESIGN AND

methodsPatients taking basal insulin (with or without oral agents) with HbA1c 7-10.5% (53-91 mmol/mol) entered a glargine standardization period, followed by randomization to albiglutide, 30 mg weekly (n = 282), subsequently uptitrated to 50 mg, if necessary, or thrice-daily prandial lispro (n = 281) while continuing metformin and/or pioglitazone. Glargine was titrated to fasting plasma glucose of <5.6 mmol/L, and lispro was adjusted based on glucose monitoring. The primary end point was the difference in the HbA1c change from baseline at week 26.

resultsAt week 26, HbA1c decreased from baseline by -0.82 ± SE 0.06% (9.0 mmol/mol) with albiglutide and -0.66 ± 0.06% (7.2 mmol/mol) with lispro; treatment difference, -0.16% (95% CI -0.32 to 0.00; 1.8 mmol/mol; P < 0.0001), meeting the noninferiority end point (margin, 0.4%). Weight decreased with albiglutide but increased with lispro (-0.73 ± 0.19 kg vs. +0.81 ± 0.19 kg). The mean glargine dose increased from 47 to 53 IU (albiglutide) and from 44 to 51 IU (lispro). Adverse events for albiglutide versus lispro included severe hypoglycemia (0 vs. 2 events), documented symptomatic hypoglycemia (15.8% vs. 29.9%), nausea (11.2% vs. 1.4%), vomiting (6.7% vs. 1.4%), and injection site reactions (9.5% vs. 5.3%).

conclusionsWeekly albiglutide is a simpler therapeutic option than thrice-daily lispro for advancing basal insulin glargine therapy, resulting in comparable HbA1c reduction with weight loss and lower hypoglycemia risk.

Indexed as

Administration, OralAdultAgedBlood GlucoseDiabetes Mellitus, Type 2Drug Administration ScheduleDrug SubstitutionDrug Therapy, CombinationFemaleGlucagon-Like Peptide 1Glucagon-Like Peptide-1 ReceptorGlycated HemoglobinHumansHypoglycemic AgentsInsulinInsulin GlargineBlood GlucoseGLP1R protein, humanGlucagon-Like Peptide 1Glucagon-Like Peptide-1 ReceptorGlycated HemoglobinHypoglycemic AgentsInsulinInsulin GlargineInsulin LisproInsulin, Long-ActingMetforminPioglitazoneReceptors, GlucagonrGLP-1 proteinThiazolidinediones

Identifiers

PMID24898300
OpenAlexW2137562839

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.