Evidence map›GLP-1 receptor agonists × body weight & composition›PMID 33667417›Full record

Trial reportLancet (London, England)2021

Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial.

Melanie Davies, Louise Færch, Ole K Jeppesen, Arash Pakseresht, Sue D Pedersen, Leigh Perreault, Julio Rosenstock, Iichiro Shimomura, Adie Viljoen, Thomas A Wadden and 2 more

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

Trial report in Lancet (London, England), 2021. The graph read 1 number from its abstract, feeding 1 cell of the map, but it casts no vote: it reports several registered trials together, and each votes through its own primary report. It reports registered trial NCT03552757. Cited by 727 papers, 19 of them syntheses that pooled it.

1number the graph read from it
0cells of the map it votes in
727citing papers in PubMed, 19 pooled it
102.9field-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.

← favours the comparatorfavours the treatment →
241 · no effect
Body weight & compositionfavours the treatment · against placebo · t2d, obesityfeeds one cell of the map
OR 4.883.58 to 6.64p<0.0001
At week 68, more patients on semaglutide 2.4 mg than on placebo achieved weight reductions of at least 5% (267 [68.8%] of 388 vs 107 [28.5%] of 376; odds ratio 4.88, 95% CI 3.58 to 6.64; p<0.0001).
FeedsGLP-1 receptor agonists×body weight & composition

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×body weight & composition

Does not voteOpen on the map →What to test next →

40 readable studies in this cell: 74 favour the treatment, 15 find no difference, 10 favour the comparator.

Belief with this paper
0.91replicated · 59 families support, 6 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
This paper’s trial, registry resultNCT03552757 · 1,210 enrolled · 2018
Δ -6.21-7.28 to -5.15
This paper’s trial, registry resultNCT03811574 · 401 enrolled · 2019
Δ -7.52-9.62 to -5.43
NCT012722193,731 enrolled · 2011
Δ -5.39-5.82 to -4.95
Coadministered Cagrilintide and Semaglutide in Adults with Overweight …PMID 40544433 · 3,400 enrolled · 2022
Δ -17.3-18.1 to -16.6
NCT017204463,297 enrolled · 2013
Δ -2.95-3.47 to -2.44
NCT035489351,961 enrolled · 2018
Δ -12.4-13.4 to -11.5
NCT039879191,879 enrolled · 2019
Δ -1.70-2.60 to -0.70
NCT026078651,864 enrolled · 2016
Δ -2.50-3.00 to -2.00
NCT056467061,407 enrolled · 2023
Δ -14.8-16.2 to -13.4
NCT018365231,398 enrolled · 2013
Δ -4.90-5.65 to -4.16
NCT007344741,202 enrolled · 2008
Δ -1.50-2.08 to -0.92
Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type…PMID 40544432 · 1,200 enrolled · 2023
Δ -10.4-11.2 to -9.50
NCT020581471,170 enrolled · 2014
Δ 14.38.37 to 20.3
NCT003184611,091 enrolled · 2006
Δ -1.29-2.16 to -0.41
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.

NCT03552757 phase3completed

Effect and Safety of Semaglutide 2.4 mg Once-weekly in Subjects With Overweight or Obesity and Type 2 Diabetes

Ran2018Enrolled1,210Registered outcomes41Posted comparisons4ConditionsObesity, OverweightArmsPlacebo II (Semaglutide), Placebo I (Semaglutide), Semaglutide 1.0 mg, Semaglutide 2.4 mg
PMID 32441473other papers from this trial
Open the trial in the graph
NCT03811574 phase3completed

Effect and Safety of Semaglutide Once-weekly in East Asian Subjects With Overweight or Obesity

Ran2019Enrolled401Registered outcomes39Posted comparisons4ConditionsObesity, OverweightArmsPlacebo (semaglutide), semaglutide
Open the trial in the graph
NCT07462663 phase4not yet recruitingstarted 2027, after this paper: background citation

SHAPE-ENDO (Strategic Hormonal Approach & Prehabilitation in Endometrial Cancer): An Open-Label, Pilot Randomized Clinical Trial Comparing Standard Immediate Surgery Versus a Multimodal Metabolic Optimization and Prehabilitation Strategy Before Surgery in Patients With Atypical Endometrial Hyperplasia or Low-Risk Endometrioid Endometrial Cancer and BMI ≥40 kg/m²

Ran2027Enrolled80Registered outcomes34Posted comparisons0ConditionsAtypical Endometrial Hyperplasia, Atypical Endometrial Hyperplasia and Endometrial Carcinoma Stage I, BMI>40, Endometrial CancerArmsDietetic-Nutritional intervention, Endometrial Biopsy With or Without Hysteroscopy, GLP-1 receptor agonist, Levonorgestrel IUD (Lng-IUD), Oral Progestins
PMID 33755728PMID 36216945PMID 29266019PMID 17096437PMID 23021687PMID 25791635PMID 27654262PMID 27901412PMID 30193337PMID 33397713PMID 34238643PMID 35314087other papers from this trial
Open the trial in the graph
NCT05870943 naunknown statusnot on this mapstarted 2023, after this paper: background citation

Hybrid Argon Plasma Coagulation and Endoscopic Sleeve Gastroplasty Trial: A Single-Center Randomized Controlled Validation Trial in a Community Setting

TypeinterventionalSponsorTrue You Weight LossRan2023 to 2025Enrolled48ConditionsObesityArmsHybrid Argon Plasma Coagulation, Endoscopic Sleeve Gastroplasty
5 · Its place in the literature

Who cites it

727 citing papers in PubMed, 19 syntheses or guidelines pooled it, 1,196 citations in OpenAlex.

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  10. The effect of GLP-1 receptor agonists on renal outcomes: a systematic review and meta-analysis.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2026
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  14. Guideline
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667 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 9 institutions in 5 countries.

Melanie DaviesDiabetes Research Centre, University of Leicester, Leicester, UK; NIHR Leicester Biomedical Research Centre, Leicester, UK.
Louise FærchNovo Nordisk, Søborg, Denmark.
Ole K JeppesenNovo Nordisk, Søborg, Denmark.
Arash PaksereshtNovo Nordisk, Søborg, Denmark.
Sue D PedersenC-ENDO Diabetes and Endocrinology Clinic Calgary, Calgary, AB, Canada.
Leigh PerreaultUniversity of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Julio RosenstockDallas Diabetes Research Center at Medical City, Dallas, TX, USA.
Iichiro ShimomuraGraduate School of Medicine, Osaka University, Suita, Osaka, Japan.
Adie ViljoenBorthwick Diabetes Research Unit, Lister Hospital, Stevenage, UK.
Thomas A WaddenPerelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Ildiko LingvayUniversity of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address: ildiko.lingvay@utsouthwestern.edu.
STEP 2 Study Group
Novo Nordisk (Denmark) · DKDallas Diabetes Research Center · USLister Hospital · GBLMC Diabetes & Endocrinology (Canada) · CANIHR Leicester Biomedical Research Centre · GBOsaka University · JPThe University of Texas Southwestern Medical Center · USUniversity of Colorado Anschutz Medical Campus · USUniversity of Pennsylvania · US

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.

backgroundThis trial assessed the efficacy and safety of the GLP-1 analogue once a week subcutaneous semaglutide 2·4 mg versus semaglutide 1·0 mg (the dose approved for diabetes treatment) and placebo for weight management in adults with overweight or obesity, and type 2 diabetes.

methodsThis double-blind, double-dummy, phase 3, superiority study enrolled adults with a body-mass index of at least 27 kg/m

findingsFrom June 4 to Nov 14, 2018, 1595 patients were screened, of whom 1210 were randomly assigned to semaglutide 2·4 mg (n=404), semaglutide 1·0 mg (n=403), or placebo (n=403) and included in the intention-to-treat analysis. Estimated change in mean bodyweight from baseline to week 68 was -9·6% (SE 0·4) with semaglutide 2·4 mg vs -3·4% (0·4) with placebo. Estimated treatment difference for semaglutide 2·4 mg versus placebo was -6·2 percentage points (95% CI -7·3 to -5·2; p<0·0001). At week 68, more patients on semaglutide 2·4 mg than on placebo achieved weight reductions of at least 5% (267 [68·8%] of 388 vs 107 [28·5%] of 376; odds ratio 4·88, 95% CI 3·58 to 6·64; p<0·0001). Adverse events were more frequent with semaglutide 2·4 mg (in 353 [87·6%] of 403 patients) and 1·0 mg (329 [81·8%] of 402) than with placebo (309 [76·9%] of 402). Gastrointestinal adverse events, which were mostly mild to moderate, were reported in 256 (63·5%) of 403 patients with semaglutide 2·4 mg, 231 (57·5%) of 402 with semaglutide 1·0 mg, and 138 (34·3%) of 402 with placebo.

interpretationIn adults with overweight or obesity, and type 2 diabetes, semaglutide 2·4 mg once a week achieved a superior and clinically meaningful decrease in bodyweight compared with placebo.

fundingNovo Nordisk.

Indexed as

AdultAgedDiabetes Mellitus, Type 2Double-Blind MethodFemaleGlucagon-Like PeptidesGlycated HemoglobinHumansHypoglycemic AgentsInjections, SubcutaneousMaleMiddle AgedObesityOverweightSemaglutideTreatment OutcomeGlucagon-Like PeptidesGlycated HemoglobinHypoglycemic AgentsSemaglutide

Identifiers

PMID33667417
OpenAlexW3133746780

What OpenQuestion 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 OpenQuestion graph.