Evidence map›Paper›PMID 30284349›Full record

ArticleDiabetes, obesity & metabolism2019

Cardiovascular safety of oral semaglutide in patients with type 2 diabetes: Rationale, design and patient baseline characteristics for the PIONEER 6 trial.

Stephen C Bain, Ofri Mosenzon, Rosario Arechavaleta, Pawel Bogdański, Abdurrahman Comlekci, Agostino Consoli, Chaicharn Deerochanawong, Kathleen Dungan, Maria C Faingold, Michael E Farkouh and 16 more

Registry-linked trialAbstract readClinical Trial Protocol
PubMed Full text at PMC Publisher
In one paragraph

Article in Diabetes, obesity & metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT02692716. Cited by 51 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed, 6 pooled it
–field-weighted citation impact
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.

NCT02692716 phase3completed

A Trial Investigating the Cardiovascular Safety of Oral Semaglutide in Subjects With Type 2 Diabetes

Ran2017Enrolled3,183Registered outcomes18Posted comparisons13ConditionsDiabetes, Diabetes Mellitus, Type 2ArmsPlacebo, semaglutide
PMID 31185157PMID 35484580PMID 29263194PMID 34277983PMID 35373893other papers from this trial
Open the trial in the graph
3 · Its place in the literature

Who cites it

51 citing papers in PubMed, 6 syntheses or guidelines pooled it.

  1. Pooled it
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  7. Effect of semaglutide on kidney function across different levels of baseline HbA1c, blood pressure, body weight and albuminuria in SUSTAIN 6 and PIONEER 6.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025
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  12. PIONEER REAL Italy: Real-World Usage of Once-Daily Oral Semaglutide in Adults with Type 2 Diabetes.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2025
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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

26 authors.

Stephen C BainDiabetes Research Unit Cymru, Swansea University Medical School, Swansea, UK.ORCID 0000-0001-8519-4964
Ofri MosenzonDiabetes Unit, Division of Internal Medicine, Hadassah Hebrew University Hospital, Jerusalem, Israel.
Rosario ArechavaletaDepartment of Endocrinology, Universidad Autonoma de Guadalajara, Jalisco, Mexico.
Pawel BogdańskiDepartment of Education and Obesity Treatment and Metabolic Disorders, Poznan University of Medical Sciences, Poznan, Poland.
Abdurrahman ComlekciDepartment of Endocrinology, Dokuz Eylul University Faculty of Medicine, Balcova, Izmir, Turkey.
Agostino ConsoliDepartment of Medicine and Aging, and Center of Aging Science and Translational Medicine (CESI-Met), "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy.
Chaicharn DeerochanawongDiabetes and Endocrinology Unit, Rajavithi Hospital, Rangsit Medical School, Bangkok, Thailand.
Kathleen DunganDivision of Endocrinology, Diabetes and Metabolism, Ohio State University, Columbus, Ohio.ORCID 0000-0003-1289-1595
Maria C FaingoldDepartment of Endocrinology and Metabolism, Dr Cesar Milstein Hospital, Buenos Aires, Argentina.
Michael E FarkouhPeter Munk Cardiac Centre, University Health Network, Department of Medicine and the Heart and Stroke Richard Lewar Centre, University of Toronto, Toronto, Ontario, Canada.
Denise R FrancoCPCLIN Clinical Research Center, São Paulo, Brazil.
Jeppe GramDepartment of Endocrinology, Hospital of Southwest Denmark, Esbjerg, Denmark.
Cristian GujaDepartment of Diabetes, Nutrition and Metabolic Diseases, University of Medicine and Pharmacy 'Carol Davila', Bucharest, Romania.ORCID 0000-0002-8703-0522
Pankaj JoshiDiabetes Care and Clinical Trials Centre, Pretoria, South Africa.
Rachid MalekDepartment of Internal Medicine, CHU Sétif, Sétif, Algeria.
Juan F Merino-TorresDepartment of Endocrinology and Nutrition, University Hospital La Fe, Valencia, Spain.
Michael A NauckDiabetes Center Bochum-Hattingen, Medical Department I, St Josef-Hospital, Ruhr-University Bochum, Bochum, Germany.ORCID 0000-0002-5749-6954
Sue D PedersenC-ENDO Diabetes and Endocrinology Clinic, Calgary, Alberta, Canada.
Wayne H-H SheuDivision of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
Robert J SilverSouthern New Hampshire Diabetes and Endocrinology, Nashua, New Hampshire.
Cees J TackDepartment of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
Nikhil TandonDepartment of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, India.
Ole K JeppesenNovo Nordisk A/S, Bagsvaerd, Denmark.
Mette StrangeNovo Nordisk A/S, Bagsvaerd, Denmark.
Mette ThomsenNovo Nordisk A/S, Bagsvaerd, Denmark.
Mansoor HusainPeter Munk Cardiac Centre, University Health Network, Department of Medicine and the Heart and Stroke Richard Lewar Centre, University of Toronto, Toronto, Ontario, Canada.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsTo assess the cardiovascular (CV) safety of oral semaglutide, the first tablet formulation of a glucagon-like peptide-1 receptor agonist. MATERIALS AND

methodsPIONEER 6 is a multinational, randomized, placebo-controlled, double-blind trial in patients with type 2 diabetes at high risk of CV events (defined as being aged ≥50 years and having established CV disease [CVD] or moderate [stage 3] chronic kidney disease [CKD], or being aged ≥60 years with ≥1 other CV risk factor). Patients were randomized to once-daily oral semaglutide (up to 14 mg) or placebo added to standard of care. The primary composite endpoint is time to first occurrence of CV death or non-fatal myocardial infarction or non-fatal stroke. The primary hypothesis was to exclude an excess in CV risk with oral semaglutide by assessing non-inferiority versus placebo for the primary endpoint (non-inferiority margin of 1.8 for the upper boundary of the 95% confidence interval of the hazard ratio). PIONEER 6 is event-driven, with follow-up continuing until accrual of at least 122 primary outcome events. There is no pre-defined minimal duration.

resultsOverall, 3183 patients have been enrolled (mean age 66.1 years, 31.6% females) in 214 sites across 21 countries. At baseline, the mean duration of diabetes was 14.9 years, mean glycated haemoglobin concentration was 66 mmol/mol (8.2%), and 84.6% of patients had established CVD/moderate CKD.

conclusionsPIONEER 6 will provide evidence regarding the CV safety of oral semaglutide in patients with type 2 diabetes and high CV risk.

Indexed as

Administration, OralAgedAged, 80 and overCardiovascular DiseasesCardiovascular SystemDiabetes Mellitus, Type 2Diabetic AngiopathiesDouble-Blind MethodEquivalence Trials as TopicFemaleGlucagon-Like PeptidesHumansHypoglycemic AgentsMaleMetforminMiddle AgedGlucagon-Like PeptidesHypoglycemic AgentsMetforminPlacebosSemaglutidecardiovascular diseasecardiovascular outcomes trialGLP-1 receptor agonistoral semaglutidetype 2 diabetes

Identifiers

PMID30284349
PMCPMC6587508

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Texttitle and abstract
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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.