Evidence mapPaperPMID 26833744Full record

Trial reportDiabetes, obesity & metabolism2016

Exposure-response analyses of liraglutide 3.0 mg for weight management.

J P H Wilding, R V Overgaard, L V Jacobsen, C B Jensen, C W le Roux

2 registry-linked trialsOpen access · hybridAbstract readClinical Trial, Phase IIClinical Trial, Phase IIIRandomized Controlled Trial
In one paragraph

Trial report in Diabetes, obesity & metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT01272219. Cited by 55 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed, 4 pooled it
5.7field-weighted citation impact, top 4% 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.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · 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.

NCT01272219 phase3completed

Effect of Liraglutide on Body Weight in Non-diabetic Obese Subjects or Overweight Subjects With Co-morbidities: A Randomised, Double-blind, Placebo Controlled, Parallel Group, Multi-centre, Multinational Trial With Stratification of Subject to Either 56 or 160 Weeks of Treatment Based on Pre-diabetes Status at Randomisation

Ran2011Enrolled3,731Registered outcomes12Posted comparisons4ConditionsMetabolism and Nutrition Disorder, ObesityArmsliraglutide, Placebo
Open the trial in the graph
NCT01272232 phase3completed

Effect of Liraglutide on Body Weight in Overweight or Obese Subjects With Type 2 Diabetes: A 56 Week Randomised, Double-blind, Placebo-controlled, Three Armed Parallel Group, Multi-centre, Multinational Trial With a 12 Week Observational Follow-up Period

Ran2011Enrolled846Registered outcomes12Posted comparisons27ConditionsMetabolism and Nutrition Disorder, ObesityArmsliraglutide, Placebo
Open the trial in the graph
3 · Its place in the literature

Who cites it

55 citing papers in PubMed, 4 syntheses or guidelines pooled it, 97 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 3 countries.

J P H WildingDepartment of Obesity and Endocrinology, University of Liverpool, Liverpool, UK.
R V OvergaardMedical Affairs, GLP-1 and Obesity, Novo Nordisk A/S, Søborg, Denmark.
L V JacobsenMedical Affairs, GLP-1 and Obesity, Novo Nordisk A/S, Søborg, Denmark.
C B JensenMedical Affairs, GLP-1 and Obesity, Novo Nordisk A/S, Søborg, Denmark.
C W le RouxDiabetes Complications Research Centre, Conway Institute, University College Dublin, Dublin, Ireland.
Novo Nordisk (Denmark) · DKUniversity College Dublin · IEUniversity of Liverpool · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsLiraglutide 3.0 mg, an acylated GLP-1 analogue approved for weight management, lowers body weight through decreased energy intake. We conducted exposure-response analyses to provide important information on individual responses to given drug doses, reflecting inter-individual variations in drug metabolism, absorption and excretion.

methodsWe report efficacy and safety responses across a wide range of exposure levels, using data from one phase II (liraglutide doses 1.2, 1.8, 2.4 and 3.0 mg), and two phase IIIa [SCALE Obesity and Prediabetes (3.0 mg); SCALE Diabetes (1.8; 3.0 mg)] randomized, placebo-controlled trials (n = 4372).

resultsThere was a clear exposure-weight loss response. Weight loss increased with greater exposure and appeared to level off at the highest exposures associated with liraglutide 3.0 mg in most individuals, but did not fully plateau in men. In individuals with overweight/obesity and comorbid type 2 diabetes, there was a clear exposure-glycated haemoglobin (HbA1c) relationship. HbA1c reduction increased with higher plasma liraglutide concentration (plateauing at ∼21 nM); however, for individuals with baseline HbA1c >8.5%, HbA1c reduction did not fully plateau. No exposure-response relationship was identified for any safety outcome, with the exception of gastrointestinal adverse events (AEs). Individuals with gallbladder AEs, acute pancreatitis or malignant/breast/benign colorectal neoplasms did not have higher liraglutide exposure compared with the overall population.

conclusionsThese analyses support the use of liraglutide 3.0 mg for weight management in all subgroups investigated; weight loss increased with higher drug exposure, with no concomitant deterioration in safety/tolerability besides previously known gastrointestinal side effects.

Indexed as

Glucagon-Like Peptide-1 Receptor AgonistsAppetite DepressantsBody Mass IndexCohort StudiesCombined Modality TherapyDiabetes Mellitus, Type 2Diet, ReducingDose-Response Relationship, DrugDouble-Blind MethodExerciseFemaleGlucagon-Like Peptide-1 ReceptorHumansHypoglycemic AgentsIncretinsLiraglutideAppetite DepressantsGlucagon-Like Peptide-1 ReceptorGlucagon-Like Peptide-1 Receptor AgonistsHypoglycemic AgentsIncretinsLiraglutidebody weightglucagon-like peptide-1incretinpharmacokinetic

Identifiers

PMID26833744
PMCPMC5069568
OpenAlexW2340697629

What Socratic holds

Texttitle and abstract
LicenceCC BY-NC-ND
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.