Evidence mapPaperPMID 28386912Full record

ArticleDiabetes, obesity & metabolism2017

Neuropsychiatric safety with liraglutide 3.0 mg for weight management: Results from randomized controlled phase 2 and 3a trials.

Patrick M O'Neil, Vanita R Aroda, Arne Astrup, Robert Kushner, David C W Lau, Thomas A Wadden, Jason Brett, Ana-Paula Cancino, John P H Wilding, Satiety and Clinical Adiposity - Liraglutide Evidence in individuals with and without diabetes (SCALE) study groups

6 registry-linked trialsOpen access · hybridAbstract read
In one paragraph

Article in Diabetes, obesity & metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT00422058. Cited by 53 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed, 3 pooled it
3.4field-weighted citation impact, top 8% 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.

NCT00422058 phase2completed

Effect of Liraglutide on Body Weight in Obese Subjects Without Diabetes: A 20-week Randomised, Double-blind, Placebo-controlled, Six Armed Parallel Group, Multi-centre, Multinational Trial With an Open Label Orlistat Comparator Arm and With an 84-week Extension Period

Ran2007Enrolled564Registered outcomes20Posted comparisons0ConditionsMetabolism and Nutrition Disorder, ObesityArmsliraglutide, Orlistat, Placebo
Open the trial in the graph
NCT00781937 phase3completed

Effect of Liraglutide on Long-term Weight Maintenance and Additional Weight Loss Induced by a 4 to 12 Week Low Calorie Diet in Obese Subjects; A 56 Week Randomised, Double-blind, Placebo Controlled, Parallel Group, Multicentre Trial With a 12 Week Follow-up Period

Ran2008Enrolled422Registered outcomes26Posted comparisons24ConditionsMetabolism and Nutrition Disorder, ObesityArmsliraglutide, Placebo
Open the trial in the graph
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
NCT01557166 phase3completed

Effect of Liraglutide in Obese Subjects With Moderate or Severe Obstructive Sleep Apnoea. A 32 Week Randomised, Double-blind, Placebo-controlled, Parallel Group, Multi-centre and Multinational Trial

Ran2012Enrolled359Registered outcomes4Posted comparisons1ConditionsMetabolism and Nutrition Disorder, Obesity, Obstructive Sleep ApnoeaArmsliraglutide, Placebo
Open the trial in the graph
NCT06363487 nacompletednot on this mapstarted 2024, after this paper: background citation

Effects of Single-dose Semaglutide on Cognition and Energy in Healthy Volunteers

TypeinterventionalSponsorUniversity of OxfordRan2024 to 2024Enrolled70ConditionsCognitive ChangeArmsSemaglutide, 0.5 mg/mL, Placebo, 0.9% NaCl 1.5mL
3 · Its place in the literature

Who cites it

53 citing papers in PubMed, 3 syntheses or guidelines pooled it, 109 citations in OpenAlex.

  1. Association of Glucagon-Like Peptide-1 Receptor Agonists and Suicidality: A Systematic Review.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2026
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  6. Impact of semaglutide on health outcomes and mood in obese heart failure patients: a retrospective analysis.Clinical research in cardiology : official journal of the German Cardiac Society · 2026
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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

10 authors at 9 institutions in 4 countries.

Patrick M O'NeilWeight Management Center, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina.ORCID 0000-0002-0388-4046
Vanita R ArodaDepartment of Internal Medicine, Endocrinology, Diabetes & Metabolism, MedStar Health Research Institute, Georgetown University School of Medicine, Hyattsville, Maryland.
Arne AstrupDepartment of Nutrition, Exercise and Sports, University of Copenhagen, Frederiksberg C, Denmark.
Robert KushnerDepartment of Internal Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
David C W LauDepartments of Medicine and Biochemistry & Molecular Biology, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada.
Thomas A WaddenDepartment of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Jason BrettNovo Nordisk Inc., Plainsboro, New Jersey.
Ana-Paula CancinoNovo Nordisk A/S, Søborg, Denmark.
John P H WildingDepartment of Obesity and Endocrinology, Obesity and Endocrinology Clinical Research Group, University of Liverpool, Liverpool, UK.
Satiety and Clinical Adiposity - Liraglutide Evidence in individuals with and without diabetes (SCALE) study groups
Georgetown University · USMedical University of South Carolina · USNorthwestern University · USNovo Nordisk (Denmark) · DKNovo Nordisk (United States) · USUniversity of Calgary · CAUniversity of Copenhagen · DKUniversity of Liverpool · GBUniversity of Pennsylvania · US

Funding

NCATS NIH HHS UL1 TR001409
6 · The paper itself

Abstract

aimsLiraglutide, a GLP-1 receptor agonist, regulates appetite via receptors in the brain. Because of concerns regarding the potential of centrally-acting anti-obesity medications to affect mental health, pooled neuropsychiatric safety data from all phase 2 and 3a randomized, double-blind trials with liraglutide 3.0 mg were evaluated post hoc.

methodsData from the liraglutide weight-management programme were pooled. Across trials, individuals with a body mass index ≥30 or ≥27 kg/m

resultsIn the pooled analysis of 5325 randomized and exposed individuals, rates of depression (2.1 vs 2.1 events/100 person-years) and anxiety (1.9 vs 1.7 events/100 person-years) through adverse event reporting were similarly low in liraglutide and placebo groups. Nine (0.3%) individuals receiving liraglutide and 2 (0.1%) receiving placebo reported adverse events of suicidal ideation or behaviour. In phase 3a trials, mean baseline Patient Health Questionnaire-9 scores of 2.8 ± 3.0 vs 2.9 ± 3.1 for liraglutide vs placebo improved to 1.8 ± 2.7 vs 1.9 ± 2.7, respectively, at treatment end; 34/3291 individuals (1.0%) receiving liraglutide 3.0 mg vs 19/1843 (1.0%) receiving placebo reported suicidal ideation on the Columbia-Suicide Severity Rating Scale.

conclusionsResults of this exploratory pooled analysis provide no cause for concern regarding the neuropsychiatric safety of treatment with liraglutide 3.0 mg in patients similar to those included in the examined trials. Although there was a small numerical imbalance in suicidal ideation with liraglutide through adverse event reporting, no between-treatment imbalances in suicidal ideation/behaviour or depression were noted through prospective questionnaire assessments.

Indexed as

AdultAgedAnti-Obesity AgentsBrainClinical Trials, Phase II as TopicClinical Trials, Phase III as TopicDiabetes Mellitus, Type 2Dose-Response Relationship, DrugDouble-Blind MethodFemaleHumansLiraglutideMaleMental DisordersMental HealthMiddle AgedAnti-Obesity AgentsLiraglutideantiobesity drugGLP-1 analogueliraglutideobesity therapyrandomized trial

Identifiers

PMID28386912
PMCPMC5655710
OpenAlexW2611973976

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.