NCT03021187 (PIONEER 8) is a Phase 3 clinical trial of semaglutide in Diabetes, sponsored by Novo Nordisk A/S.

Who is sponsoring NCT03021187?

NCT03021187 is sponsored by Novo Nordisk A/S.

What drugs are being tested in NCT03021187?

Interventions in NCT03021187: semaglutide, semaglutide, semaglutide, placebo.

What condition does NCT03021187 study?

NCT03021187 studies Diabetes, Diabetes Mellitus, Type 2.

Is NCT03021187 still recruiting?

NCT03021187 is currently completed. Last updated 2 March 2020.

Are results published for NCT03021187?

Yes — primary outcome results have been posted to ClinicalTrials.gov. See the outcomes section above for details.

Last reviewed 2020-03-02 · How we verify

NCT03021187: PIONEER 8

Name: Drug Landscape Pharmaceutical Database
Creator: Drug Landscape
Published: 2026-01-01
License: https://creativecommons.org/licenses/by/4.0/

Efficacy and Safety of Oral Semaglutide Versus Placebo in Subjects With Type 2 Diabetes Mellitus Treated With Insulin

Completed Phase 3 Results posted Last updated 2 March 2020

What this trial tests

Phase 3 trial testing semaglutide in Diabetes in 731 participants. Completed in 22 August 2018.

Timeline

2 February 2017

Primary endpoint
18 January 2018

22 August 2018

Quick facts

Lead sponsor	Novo Nordisk A/S
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	731
Start date	2 February 2017
Primary completion	18 January 2018
Estimated completion	22 August 2018
Sites	118 locations across France, Japan, Russia, Greece, Poland, Mexico, Canada, Puerto Rico

Drugs / interventions tested

semaglutide (semaglutide) — full drug profile →
semaglutide (semaglutide) — full drug profile →
semaglutide (semaglutide) — full drug profile →
placebo

Conditions studied

Diabetes — all drugs for Diabetes →
Diabetes Mellitus, Type 2 — all drugs for Diabetes Mellitus, Type 2 →

Sponsor

Novo Nordisk A/S — full company profile →

Who can join

18 and older, any sex, with Diabetes or Diabetes Mellitus, Type 2. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in HbA1c (Week 26) Primary · Week 0, week 26

Change from baseline (week 0) in glycosylated haemoglobin (HbA1c) was evaluated at week 26. The endpoint was evaluated based on data from the in-trial observation period. In-trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. The endpoint was also analysed based on data from the on-treatment without rescue medication observation period. On-treatment without rescue medication observation period started at the date of the first dose of trial product and includes the per

In-trial

Group	Value	95% CI
Oral Semaglutide 3 mg	-0.5	± 1.0
Oral Semaglutide 7 mg	-1.0	± 1.1
Oral Semaglutide 14 mg	-1.3	± 1.1
Placebo	-0.1	± 0.9

On-treatment without rescue medication

Group	Value	95% CI
Oral Semaglutide 3 mg	-0.6	± 1.1
Oral Semaglutide 7 mg	-1.1	± 1.0
Oral Semaglutide 14 mg	-1.4	± 0.9
Placebo	-0.1	± 0.8

Change in Body Weight (Week 26) Secondary · Week 0, week 26

Change from baseline (week 0) in body weight was evaluated at week 26. The endpoint was evaluated based on data from the in-trial observation period. In-trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. The endpoint was also evaluated based on data from the on-treatment without rescue medication observation period. It started at the date of first dose of trial product and excluded the period after initiation of rescue medication and/or premature trial product discon

In trial

Group	Value	95% CI
Oral Semaglutide 3 mg	-1.4	± 3.1
Oral Semaglutide 7 mg	-2.6	± 5.2
Oral Semaglutide 14 mg	-3.7	± 4.0
Placebo	-0.5	± 2.5

On-treatment without rescue medication

Group	Value	95% CI
Oral Semaglutide 3 mg	-1.5	± 3.1
Oral Semaglutide 7 mg	-3.0	± 3.7
Oral Semaglutide 14 mg	-3.9	± 3.6
Placebo	-0.5	± 2.4

Change in HbA1c (Week 52) Secondary · Week 0, week 52

Change from baseline (week 0) in HbA1c to week 52. The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any.

Group	Value	95% CI
Oral Semaglutide 3 mg	-0.6	± 1.0
Oral Semaglutide 7 mg	-0.9	± 1.1
Oral Semaglutide 14 mg	-1.2	± 1.0
Placebo	-0.2	± 0.8

Change in Body Weight (kg) (Week 52) Secondary · Week 0, week 52

Change from baseline (week 0) in body weight to week 52. The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any.

Group	Value	95% CI
Oral Semaglutide 3 mg	-0.9	± 3.9
Oral Semaglutide 7 mg	-2.2	± 5.2
Oral Semaglutide 14 mg	-3.8	± 5.8
Placebo	0.5	± 3.2

Change in Fasting Plasma Glucose (FPG) Secondary · Week 0, week 26, week 52

Change from baseline (week 0) in FPG to week 26 and week 52. The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any.

Week 26

Group	Value	95% CI
Oral Semaglutide 3 mg	-0.45	± 3.35
Oral Semaglutide 7 mg	-1.14	± 3.08
Oral Semaglutide 14 mg	-1.36	± 2.72
Placebo	0.51	± 2.84

Week 52

Group	Value	95% CI
Oral Semaglutide 3 mg	-0.81	± 3.21
Oral Semaglutide 7 mg	-1.12	± 2.91
Oral Semaglutide 14 mg	-1.60	± 2.65
Placebo	-0.09	± 2.97

Change in Self-measured Plasma Glucose (SMPG) Mean 7-point Profile Secondary · Week 0, week 26, week 52

Change from baseline (week 0) in self-measured plasma glucose (SMPG) mean 7-point profile to week 26 and week 52. SMPG was recorded at the following 7 time points: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after dinner and at bedtime. Mean 7-point profile was defined as the area under the profile, calculated using the trapezoidal method, divided by the measurement time. The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisati

Week 26

Group	Value	95% CI
Oral Semaglutide 3 mg	-1.2	± 2.3
Oral Semaglutide 7 mg	-1.8	± 2.4
Oral Semaglutide 14 mg	-2.0	± 2.2
Placebo	-0.3	± 2.7

Week 52

Group	Value	95% CI
Oral Semaglutide 3 mg	-1.6	± 2.5
Oral Semaglutide 7 mg	-1.7	± 2.4
Oral Semaglutide 14 mg	-2.0	± 2.1
Placebo	-0.9	± 2.4

Change in SMPG Mean Postprandial Increment Over All Meals Secondary · Week 0, week 26, week 52

Change from baseline (week 0) in SMPG mean postprandial increment over all meals to week 26 and week 52. The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any.

Week 26

Group	Value	95% CI
Oral Semaglutide 3 mg	-0.3	± 2.3
Oral Semaglutide 7 mg	-0.8	± 2.6
Oral Semaglutide 14 mg	-1.2	± 2.5
Placebo	-0.1	± 2.8

Week 52

Group	Value	95% CI
Oral Semaglutide 3 mg	-0.3	± 2.3
Oral Semaglutide 7 mg	-0.7	± 2.3
Oral Semaglutide 14 mg	-0.7	± 2.3
Placebo	-0.3	± 2.4

Change in Body Weight (Percentage) Secondary · Week 0, week 26, week 52

Relative change from baseline (week 0) in body weight (%) was evaluated at weeks 26 and 52.The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any.

Week 26

Group	Value	95% CI
Oral Semaglutide 3 mg	-1.73	± 3.34
Oral Semaglutide 7 mg	-3.11	± 5.66
Oral Semaglutide 14 mg	-4.30	± 4.57
Placebo	-0.47	± 3.02

Week 52

Group	Value	95% CI
Oral Semaglutide 3 mg	-1.18	± 4.17
Oral Semaglutide 7 mg	-2.54	± 5.77
Oral Semaglutide 14 mg	-4.42	± 6.07
Placebo	0.65	± 3.72

Change in Body Mass Index Secondary · Week 0, week 26, week 52

Change from baseline (week 0) in body mass index (BMI) was evaluated at weeks 26 and 52. BMI was calculated based on body weight and height based on the formula: BMI kg/m\^2 = body weight (kg)/(Height (m) x Height (m)). Data based on in-trial observation period is presented. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any.

Week 26

Group	Value	95% CI
Oral Semaglutide 3 mg	-0.5	± 1.1
Oral Semaglutide 7 mg	-1.0	± 1.7
Oral Semaglutide 14 mg	-1.4	± 1.5
Placebo	-0.2	± 0.9

Week 52

Group	Value	95% CI
Oral Semaglutide 3 mg	-0.3	± 1.4
Oral Semaglutide 7 mg	-0.8	± 1.8
Oral Semaglutide 14 mg	-1.4	± 2.1
Placebo	0.2	± 1.2

Change in Waist Circumference Secondary · Week 0, week 26, week 52

Change from baseline (week 0) in waist circumference was evaluated at weeks 26 and 52.The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any.

Week 26

Group	Value	95% CI
Oral Semaglutide 3 mg	-0.9	± 4.1
Oral Semaglutide 7 mg	-2.3	± 5.1
Oral Semaglutide 14 mg	-3.6	± 4.9
Placebo	-0.6	± 3.6

Week 52

Group	Value	95% CI
Oral Semaglutide 3 mg	-0.8	± 4.8
Oral Semaglutide 7 mg	-2.3	± 5.1
Oral Semaglutide 14 mg	-4.0	± 6.8
Placebo	0.3	± 4.1

Change in Total Cholesterol - Ratio to Baseline Secondary · Week 0, week 26, week 52

Change from baseline in total cholesterol (mmol/L) is presented as ratio to baseline at week 26 and week 52. Results are based on the data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any.

Week 26

Group	Value	95% CI
Oral Semaglutide 3 mg	0.99	± 15.5
Oral Semaglutide 7 mg	0.95	± 18.7
Oral Semaglutide 14 mg	0.95	± 17.3
Placebo	1.03	± 15.4

Week 52

Group	Value	95% CI
Oral Semaglutide 3 mg	0.98	± 18.2
Oral Semaglutide 7 mg	0.97	± 19.2
Oral Semaglutide 14 mg	0.95	± 18.1
Placebo	1.00	± 17.6

Change in LDL Cholesterol - Ratio to Baseline Secondary · Week 0, week 26, week 52

Change from baseline in LDL cholesterol (mmol/L) is presented as ratio to baseline at week 26 and week 52. Results are based on the data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any.

Week 26

Group	Value	95% CI
Oral Semaglutide 3 mg	0.98	± 27.1
Oral Semaglutide 7 mg	0.93	± 30.2
Oral Semaglutide 14 mg	0.93	± 24.5
Placebo	1.03	± 25.9

Week 52

Group	Value	95% CI
Oral Semaglutide 3 mg	0.97	± 29.2
Oral Semaglutide 7 mg	0.96	± 29.4
Oral Semaglutide 14 mg	0.95	± 27.6
Placebo	1.00	± 28.3

Adverse events — posted to ClinicalTrials.gov

Time frame: Week 0 to week 57 (52 weeks treatment period + 5 weeks follow-up period). Results are based on the safety analysis set (SAS), which comprised all randomised participants who received at least one dose of trial product.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Oral Semaglutide 3 mg

Serious: 25/184 (14%)

Deaths: 0/184

Oral Semaglutide 7 mg

Serious: 19/181 (10%)

Deaths: 0/181

Oral Semaglutide 14 mg

Serious: 12/181 (7%)

Deaths: 3/181

Placebo

Serious: 17/184 (9%)

Deaths: 0/184

Serious adverse events (88 terms)

Reaction	System	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg	Placebo
Angina unstable	Cardiac disorders	—	—	—	—
Hypoglycaemic unconsciousness	Nervous system disorders	—	—	—	—
Ischaemic stroke	Nervous system disorders	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—
Orthostatic hypotension	Vascular disorders	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—
Acute kidney injury	Renal and urinary disorders	—	—	—	—
Acute myocardial infarction	Cardiac disorders	—	—	—	—
Adenocarcinoma of colon	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—
Angina pectoris	Cardiac disorders	—	—	—	—
Aortic stenosis	Vascular disorders	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—
Atrial flutter	Cardiac disorders	—	—	—	—
Brain stem infarction	Nervous system disorders	—	—	—	—
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—
Carbuncle	Infections and infestations	—	—	—	—
Cardiac failure	Cardiac disorders	—	—	—	—
Cardiac failure chronic	Cardiac disorders	—	—	—	—
Carpal tunnel syndrome	Nervous system disorders	—	—	—	—
Cataract	Eye disorders	—	—	—	—
Cellulitis	Infections and infestations	—	—	—	—
Cerebral infarction	Nervous system disorders	—	—	—	—
Cervical spinal stenosis	Musculoskeletal and connective tissue disorders	—	—	—	—
Chest pain	General disorders	—	—	—	—

Other adverse events (10 terms — click to expand)

Reaction	System	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg	Placebo
Nausea	Gastrointestinal disorders	—	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—
Abdominal discomfort	Gastrointestinal disorders	—	—	—	—
Hypertension	Vascular disorders	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—

Most-reported serious reactions: Angina unstable, Hypoglycaemic unconsciousness, Ischaemic stroke, Nausea, Orthostatic hypotension, Vomiting, Acute kidney injury, Acute myocardial infarction.

Data from ClinicalTrials.gov NCT03021187 adverse events section.

Sponsor's own description

This trial is conducted globally. The aim of the trial is to investigate the efficacy and safety of oral semaglutide versus placebo in subjects with Type 2 Diabetes Mellitus treated with insulin. All subjects should continue their pre-trial insulin therapy (basal, basal-bolus or premixed regimen including combinations of soluble insulins) throughout the trial. Subjects treated with metformin in addition to insulin treatment must continue their metformin treatment throughout the entire trial.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

Efficacy, Safety, and Tolerability of Oral Semaglutide Versus Placebo Added to Insulin With or Without Metformin in Patients With Type 2 Diabetes: The PIONEER 8 Trial.
Zinman B, Aroda VR, Buse JB, Cariou B, et al · · 2019 · cited 197× · PMID 31530667 · DOI 10.2337/dc19-0898
Semaglutide (SUSTAIN and PIONEER) reduces cardiovascular events in type 2 diabetes across varying cardiovascular risk.
Husain M, Bain SC, Jeppesen OK, Lingvay I, et al · · 2020 · cited 144× · PMID 31903692 · DOI 10.1111/dom.13955
Semaglutide, a glucagon like peptide-1 receptor agonist with cardiovascular benefits for management of type 2 diabetes.
Mahapatra MK, Karuppasamy M, Sahoo BM. · · 2022 · cited 92× · PMID 34993760 · DOI 10.1007/s11154-021-09699-1
Efficacy, safety and cardiovascular outcomes of once-daily oral semaglutide in patients with type 2 diabetes: The PIONEER programme.
Thethi TK, Pratley R, Meier JJ. · · 2020 · cited 90× · PMID 32267058 · DOI 10.1111/dom.14054
Therapeutic Potential of Semaglutide, a Newer GLP-1 Receptor Agonist, in Abating Obesity, Non-Alcoholic Steatohepatitis and Neurodegenerative diseases: A Narrative Review.
Mahapatra MK, Karuppasamy M, Sahoo BM. · · 2022 · cited 84× · PMID 35650449 · DOI 10.1007/s11095-022-03302-1
Levels of circulating semaglutide determine reductions in HbA1c and body weight in people with type 2 diabetes.
Overgaard RV, Hertz CL, Ingwersen SH, Navarria A, et al · · 2021 · cited 65× · PMID 34622228 · DOI 10.1016/j.xcrm.2021.100387
Effects of semaglutide on risk of cardiovascular events across a continuum of cardiovascular risk: combined post hoc analysis of the SUSTAIN and PIONEER trials.
Husain M, Bain SC, Holst AG, Mark T, et al · · 2020 · cited 29× · PMID 32998732 · DOI 10.1186/s12933-020-01106-4
Glucagon-Like Peptide-1 Receptor Agonists and Major Adverse Cardiovascular Events in Patients With and Without Diabetes: A Meta-Analysis of Randomized-Controlled Trials.
Hosseinpour A, Sood A, Kamalpour J, Zandi E, et al · · 2024 · cited 20× · PMID 38953365 · DOI 10.1002/clc.24314

Verify or expand the search:

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Trials testing the same drug.

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Other recruiting trials for Diabetes

Currently open trials in the same condition.

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Other Novo Nordisk A/S trials

Trials by the same sponsor.

NCT07357740 — A Research Study to Compare Two Different Versions of Injectable CagriSema in People With Type 2 Diabetes · Phase 2 · not yet recruiting
NCT07282613 — A Research Study to See How Much CagriSema Lowers Blood Sugar and Body Weight Compared to Placebo in Children and Adoles · Phase 3 · not yet recruiting
NCT07357766 — A Research Study to Compare Different Versions of Injectable CagriSema and Placebo in People With Excess Body Weight · Phase 3 · not yet recruiting
NCT07564414 — A Research Study to Look at How Two Different Doses of CagriSema and One Dose of Semaglutide Help People Living With Obe · Phase 3 · not yet recruiting
NCT07400107 — AMAZE 8: A Research Study Investigating How Well the Medicine NNC0487-0111 Compared to Semaglutide Helps People With Exc · Phase 3 · not yet recruiting

Verify against primary sources

ClinicalTrials.gov — authoritative US registry record
WHO ICTRP — international registry index
EU Clinical Trials Register
Sponsor press releases (Google)

Data sources for this page

Trial protocol + status: ClinicalTrials.gov NCT03021187 (US National Library of Medicine, public domain)
Publications: Europe PMC API search by NCT ID, retrieved 10 June 2026
Drug + disease cross-links: matched in real time against Drug Landscape's normalised drug + company + condition tables
Sponsor: as reported to ClinicalTrials.gov by Novo Nordisk A/S
Last refreshed: 2 March 2020

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03021187.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing

NCT03021187: PIONEER 8

Quick facts

Drugs / interventions tested

Conditions studied

Sponsor

Who can join

Results — posted to ClinicalTrials.gov

Adverse events — posted to ClinicalTrials.gov

Serious adverse events (88 terms)

Sponsor's own description

Publications & conference data

Related trials

Other trials of semaglutide

Other recruiting trials for Diabetes

Other Novo Nordisk A/S trials

Verify against primary sources