Evidence map›GLP-1 receptor agonists × glycemic control›PMID 25011946›Full record

Trial reportDiabetes care2014

Glucagon-like peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes.

Michaela Diamant, Michael A Nauck, Rimma Shaginian, James K Malone, Simon Cleall, Matthew Reaney, Danielle de Vries, Byron J Hoogwerf, Leigh MacConell, Bruce H R Wolffenbuttel and 1 more

4 registry-linked trialsAbstract readMulticenter 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 reports registered trial NCT00960661. Cited by 74 papers, 10 of them syntheses that pooled it.

1number the graph read from it
0cells of the map it votes in
74citing papers in PubMed, 10 pooled it
24.2field-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 · obesity, t2dfeeds 2 cells of the map
Δ -0.04-0.18 to 0.11
At 30 weeks postrandomization, mean HbA1c changes were noninferior for exenatide compared with lispro (-1.13 and -1.10%, respectively); treatment differences were -0.04 (95% CI -0.18, 0.11) in per-protocol (n = 510) and -0.03 (95% CI -0.16, 0.11) in intent-to-treat (n = 627) populations.
FeedsGLP-1 receptor agonists×glycemic controlInsulin×glycemic control

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

Belief with this paper
0.91replicated · 68 families support, 7 contradict · against placebo
Without it
0.92This paper moves it by −0.01.
← favours the treatmentfavours the comparator →
0 · no effect
This paper’s trial, registry resultNCT00960661 · 1,036 enrolled · 2009
Δ -0.04-0.18 to 0.11
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

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
This paper’s trial, registry resultNCT00960661 · 1,036 enrolled · 2009
Δ -0.04-0.18 to 0.11
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
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
NCT04093752917 enrolled · 2019
Δ -1.49-1.69 to -1.29
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.

NCT00960661 phase3completed

A Randomized Trial Comparing Two Therapies: Basal Insulin/Glargine, Exenatide and Metformin Therapy (BET) or Basal Insulin/Glargine, Bolus Insulin Lispro and Metformin Therapy (BBT) in Subjects With Type 2 Diabetes Who Were Previously Treated by Basal Insulin Glargine With Either Metformin or Metformin and Sulfonylurea

Ran2009Enrolled1,036Registered outcomes13Posted comparisons1ConditionsType 2 Diabetes MellitusArmsexenatide, Insulin/ Glargine, insulin lispro, Metformin
Open the trial in the graph
NCT02846233 nacompletedstarted 2016, after this paper: background citation

Is the Stepping-down Approach a Better Option Than Multiple Daily Injections in Patients With Chronic Poorly-controlled Diabetes on Advanced Insulin Therapy?

Ran2016Enrolled22Registered outcomes8Posted comparisons0ConditionsType 2 Diabetes MellitusArmsBasal Insulin, GLP1 receptor agonist, Metformin, SGLT2 inhibitor
PMID 27222560PMID 26731084other papers from this trial
Open the trial in the graph
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
PMID 18784090PMID 24898300PMID 15111485PMID 27659408PMID 20403888PMID 9742976PMID 9449682PMID 28803820PMID 28724168PMID 27913575PMID 26642233PMID 26260346other papers from this trial
Open the trial in the graph
NCT06363747 phase2 / phase3active not recruitingnot on this mapstarted 2024, after this paper: background citation

The Medically Reproducing Bariatric Surgery (MRB) II Study: SEMAGLUTIDE Followed by OPTIFAST in Veterans With Type 2 Diabetes

TypeinterventionalSponsorDurham VA Medical CenterRan2024 to 2025Enrolled50ConditionsType 2 Diabetes, ObesityArmsVery Low Calorie Diet
5 · Its place in the literature

Who cites it

74 citing papers in PubMed, 10 syntheses or guidelines pooled it, 220 citations in OpenAlex.

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

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

11 authors at 6 institutions in 3 countries.

Michaela DiamantDiabetes Center, VU University Medical Center, Amsterdam, the Netherlands.
Michael A NauckDiabetes Center, Bad Lauterberg, Germany.
Rimma ShaginianEli Lilly and Company, Houten, the Netherlands.
James K MaloneEli Lilly and Company, Indianapolis, IN.
Simon CleallEli Lilly and Company, Windlesham, U.K.
Matthew ReaneyEli Lilly and Company, Windlesham, U.K.
Danielle de VriesEli Lilly and Company, Houten, the Netherlands.
Byron J HoogwerfEli Lilly and Company, Indianapolis, IN.
Leigh MacConellBristol-Myers Squibb Company, San Diego, CA.
Bruce H R WolffenbuttelDepartment of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands bwo@umcg.nl.
4B Study Group
Eli Lilly (United States) · USAmsterdam UMC Location VUmc · NLBristol-Myers Squibb (United States) · USDiabeteszentrum Bad Lauterberg · DEEli Lilly (Netherlands) · NLUniversity Medical Center Groningen · NL

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.

objectiveMealtime insulin is commonly added to manage hyperglycemia in type 2 diabetes when basal insulin is insufficient. However, this complex regimen is associated with weight gain and hypoglycemia. This study compared the efficacy and safety of exenatide twice daily or mealtime insulin lispro in patients inadequately controlled by insulin glargine and metformin despite up-titration. RESEARCH DESIGN AND

methodsIn this 30-week, open-label, multicenter, randomized, noninferiority trial with 12 weeks prior insulin optimization, 627 patients with insufficient postoptimization glycated hemoglobin A1c (HbA1c) were randomized to exenatide (10-20 µg/day) or thrice-daily mealtime lispro titrated to premeal glucose of 5.6-6.0 mmol/L, both added to insulin glargine (mean 61 units/day at randomization) and metformin (mean 2,000 mg/day).

resultsRandomization HbA1c and fasting glucose (FG) were 8.3% (67 mmol/mol) and 7.1 mmol/L for exenatide and 8.2% (66 mmol/mol) and 7.1 mmol/L for lispro. At 30 weeks postrandomization, mean HbA1c changes were noninferior for exenatide compared with lispro (-1.13 and -1.10%, respectively); treatment differences were -0.04 (95% CI -0.18, 0.11) in per-protocol (n = 510) and -0.03 (95% CI -0.16, 0.11) in intent-to-treat (n = 627) populations. FG was lower with exenatide than lispro (6.5 vs. 7.2 mmol/L; P = 0.002). Weight decreased with exenatide and increased with lispro (-2.5 vs. +2.1 kg; P < 0.001). More patients reported treatment satisfaction and better quality of life with exenatide than lispro, although a larger proportion of patients with exenatide experienced treatment-emergent adverse events. Exenatide resulted in fewer nonnocturnal hypoglycemic episodes but more gastrointestinal adverse events than lispro.

conclusionsAdding exenatide to titrated glargine with metformin resulted in similar glycemic control as adding lispro and was well tolerated. These findings support exenatide as a noninsulin addition for patients failing basal insulin.

Indexed as

AgedBlood GlucoseBody WeightDiabetes Mellitus, Type 2Drug Administration ScheduleExenatideFemaleGlucagon-Like Peptide-1 ReceptorGlycated HemoglobinHumansHyperglycemiaHypoglycemiaHypoglycemic AgentsInsulinInsulin GlargineInsulin LisproBlood GlucoseExenatideGLP1R protein, humanGlucagon-Like Peptide-1 ReceptorGlycated HemoglobinHypoglycemic AgentsInsulinInsulin GlargineInsulin LisproInsulin, Long-ActingMetforminPeptidesReceptors, GlucagonVenoms

Identifiers

PMID25011946
OpenAlexW2106758571

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.