Evidence map›Paper›PMID 34514682›Full record

Trial reportDiabetes, obesity & metabolism2022

Gastrointestinal tolerability of once-weekly semaglutide 2.4 mg in adults with overweight or obesity, and the relationship between gastrointestinal adverse events and weight loss.

Sean Wharton, Salvatore Calanna, Melanie Davies, Dror Dicker, Bryan Goldman, Ildiko Lingvay, Ofri Mosenzon, Domenica M Rubino, Mette Thomsen, Thomas A Wadden and 1 more

Open access · hybridAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Diabetes, obesity & metabolism, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed, 6 pooled it
11.4field-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.

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

77 citing papers in PubMed, 6 syntheses or guidelines pooled it, 143 citations in OpenAlex.

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  13. Functional segregation of body-brain signals in the area postrema.bioRxiv : the preprint server for biology · 2026
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17 more citing papers are in PubMed but not listed here.

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

11 authors at 9 institutions in 5 countries.

Sean WhartonYork University, McMaster University and Wharton Weight Management Clinic, Toronto, Ontario, Canada.ORCID 0000-0003-0111-1530
Salvatore CalannaNovo Nordisk A/S, Søborg, Denmark.
Melanie DaviesDiabetes Research Centre, University of Leicester, Leicester, UK.ORCID 0000-0002-9987-9371
Dror DickerInternal Medicine Department & Obesity Clinic, Hasharon Hospital-Rabin Medical Center, Petach-Tikva, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Bryan GoldmanNovo Nordisk A/S, Søborg, Denmark.
Ildiko LingvayDepartments of Internal Medicine/Endocrinology and Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA.ORCID 0000-0001-7006-7401
Ofri MosenzonDiabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center; Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.ORCID 0000-0002-5702-7584
Domenica M RubinoWashington Center for Weight Management and Research, Arlington, Virginia, USA.
Mette ThomsenNovo Nordisk A/S, Søborg, Denmark.
Thomas A WaddenDepartment of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Sue D PedersenC-ENDO Diabetes & Endocrinology Clinic Calgary, Calgary, Alberta, Canada.
Novo Nordisk (Denmark) · DKHebrew University of Jerusalem · ILLMC Diabetes & Endocrinology (Canada) · CATel Aviv University · ILThe University of Texas Southwestern Medical Center · USUniversity of Leicester · GBUniversity of Pennsylvania · USWashington Center for Weight Management and Research · USYork University · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimWe evaluated gastrointestinal (GI) adverse events (AEs) with once-weekly semaglutide 2.4 mg in adults with overweight or obesity and their contribution to weight loss (WL). MATERIALS AND

methodsAE analyses pooled data from the Semaglutide Treatment Effect in People With Obesity (STEP) 1-3 trials for participants randomized to 68 weeks of semaglutide 2.4 mg (n = 2117) or placebo (n = 1262). WL was analysed by presence/absence of GI AEs. Mediation analysis estimated WL effects mediated by and unrelated to GI AEs. GI tolerability with semaglutide 2.4 mg maintenance and cessation after dose escalation was evaluated using STEP 4 data among 803 participants tolerating 20 weeks of semaglutide run-in.

resultsGI AEs were more common with semaglutide 2.4 mg than placebo, with most frequently nausea (43.9% vs. 16.1% of participants), diarrhoea (29.7% vs. 15.9%), vomiting (24.5% vs. 6.3%) and constipation (24.2% vs. 11.1%). Most GI AEs with semaglutide were non-serious (99.5% of AEs), mild-to-moderate (98.1%), transient and occurred most frequently during/shortly after dose escalation. Few semaglutide-treated participants (4.3%) permanently discontinued treatment for GI AEs. In STEP 1-3, mean WL with semaglutide 2.4 mg was similar in participants without (9.6%-17.1%) versus with GI AEs (11.4%-17.7%). Consistent with this observation, mediation analysis found that GI AEs contributed little to semaglutide-induced WL: of the additional 7.6%-14.4% WL with semaglutide versus placebo, <1 percentage point was mediated by GI AEs. In STEP 4, semaglutide 2.4 mg maintenance was well tolerated.

conclusionsGI AEs were more common with semaglutide 2.4 mg than placebo, but typically mild-to-moderate and transient. Semaglutide-induced WL was largely independent of GI AEs.

Indexed as

Diabetes Mellitus, Type 2OverweightAdultDouble-Blind MethodGlucagon-Like PeptidesHumansHypoglycemic AgentsInjections, SubcutaneousObesitySemaglutideWeight LossGlucagon-Like PeptidesHypoglycemic AgentsSemaglutideantiobesity drugGLP-1 analogueobesity therapyphase III studyrandomized trialweight control

Identifiers

PMID34514682
PMCPMC9293236
OpenAlexW3199001556

What Socratic holds

Texttitle and abstract
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.