Skip to content

Trial · Interventional

CompletedPhase 3Results postedRegistry data

Efficacy and Long-term Safety of Oral Semaglutide Versus Sitagliptin in Subjects With Type 2 Diabetes

Short name PIONEER 3

NCTNCT02607865 (opens ClinicalTrials.gov in a new tab)Other idNN9924-4222Other id2015-001351-71Other idU1111-1168-4339Other idJAPIC
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Completed
Phase
Phase 3
Enrollment
1,864 participants (actual)
Sponsor
Novo Nordisk A/S · Industry
Design
Randomized · Double masking
Countries
15 countries

United States, Argentina, Brazil, France, Germany, India, Israel, Japan, Mexico, Romania, Russia, South Africa, Turkey (Türkiye), Ukraine, United Kingdom

Start
15 Feb 2016
Primary completion
14 Feb 2017
Completion
28 Mar 2018
First posted
18 Nov 2015 (estimated)
Last update posted
20 Jul 2022
Conditions
Diabetes · Diabetes Mellitus, Type 2

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2016201720182019
  1. Ph 3

    PIONEER 3

    NCT02607865

    15 Feb 2016 to 28 Mar 2018

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

This trial is conducted globally. The aim of the trial is to investigate efficacy and long-term safety of oral semaglutide versus sitagliptin in subjects with type 2 diabetes.

Interventions

  • semaglutideDrug
  • sitagliptinDrug
  • placeboDrug

Arms4

  • Experimental

    Semaglutide 3 mg

  • Experimental

    Semaglutide 7 mg

  • Experimental

    Semaglutide 14 mg

  • Active comparator

    Sitagliptin 100 mg

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Change in HbA1c: Week 26

    Time frame · Week 0, week 26

    Registry description

    Change from baseline (week 0) in glycosylated haemoglobin (HbA1c) was evaluated at week 26. The endpoint was evaluated based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. The endpoint was also evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.

Secondary outcomes(20)

  1. Change in Body Weight: Week 26

    Time frame · Week 0, week 26

    Registry description

    Change from baseline (week 0) in body weight was evaluated at week 26. The endpoint was evaluated based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. The endpoint was also evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.

  2. Change in HbA1c: Weeks 52 and 78

    Time frame · Week 0, week 52, week 78

    Registry description

    Change from baseline (week 0) in HbA1c was evaluated at weeks 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  3. Change in Body Weight (kg): Weeks 52 and 78

    Time frame · Week 0, week 52, week 78

    Registry description

    Change from baseline (week 0) in body weight was evaluated at weeks 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  4. Change in Body Weight (%)

    Time frame · Week 0, week 26, week 52, week 78

    Registry description

    Relative change from baseline (week 0) in body weight (kg) was evaluated at weeks 26, 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  5. Change in FPG

    Time frame · Week 0, week 26, week 52, week 78

    Registry description

    Change from baseline (week 0) in fasting plasma glucose (FPG) was evaluated at weeks 26, 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  6. Change in BMI

    Time frame · Week 0, week 26, week 52, week 78

    Registry description

    Change from baseline (week 0) in body mass index (BMI) was evaluated at weeks 26, 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  7. Change in Waist Circumference

    Time frame · Week 0, week 26, week 52, week 78

    Registry description

    Change from baseline (week 0) in waist circumference was evaluated at weeks 26, 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  8. Change in Total Cholesterol (Ratio to Baseline)

    Time frame · Week 0, week 26, week 52, week 78

    Registry description

    Change from baseline (week 0) in total cholesterol (mmol/L) at weeks 26, 52 and 78 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  9. Change in LDL Cholesterol (Ratio to Baseline)

    Time frame · Week 0, week 26, week 52, week 78

    Registry description

    Change from baseline (week 0) in low-density lipoprotein (LDL) cholesterol (mmol/L) at weeks 26, 52 and 78 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  10. Change in VLDL Cholesterol (Ratio to Baseline)

    Time frame · Week 0, week 26, week 52, week 78

    Registry description

    Change from baseline (week 0) in very-low-density lipoprotein (VLDL) cholesterol (mmol/L) at weeks 26, 52 and 78 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  11. Change in HDL Cholesterol (Ratio to Baseline)

    Time frame · Week 0, week 26, week 52, week 78

    Registry description

    Change from baseline (week 0) in high-density lipoprotein (HDL) cholesterol (mmol/L) at weeks 26, 52 and 78 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  12. Change in Triglycerides (Ratio to Baseline)

    Time frame · Week 0, week 26, week 52, week 78

    Registry description

    Change from baseline (week 0) in triglycerides (mmol/L) at weeks 26, 52 and 78 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  13. Change in Free Fatty Acids (Ratio to Baseline)

    Time frame · Week 0, week 26, week 52, week 78

    Registry description

    Change from baseline (week 0) in free fatty acids (FFA) (mmol/L) at weeks 26, 52 and 78 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. Because of an issue with the handling of the blood samples for FFA, all FFA data were considered invalid for this trial; thus, no conclusion with regards to FFA levels can be made based on the data presented here.

  14. Change in SMPG - Mean 7-point Profile

    Time frame · Week 0, week 26, week 52, week 78

    Registry description

    Change from baseline (week 0) in mean 7-point self-measured plasma glucose (SMPG) profile. 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. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  15. Change in SMPG - Mean Postprandial Increment Over All Meals

    Time frame · Week 0, week 26, week 52, week 78

    Registry description

    Change from baseline (week 0) in the average of the post-prandial increments over all meals was evaluated at weeks 26, 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  16. Participants Who Achieve HbA1c <7.0% (53 mmol/Mol) ADA Target (Yes/no)

    Time frame · Week 26, week 52, week 78

    Registry description

    Participants who achieved HbA1c \<7.0% (American Diabetes Association (ADA) target) (yes/no), was evaluated at weeks 26, 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  17. Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol) AACE Target (Yes/no)

    Time frame · Week 26, week 52, week 78

    Registry description

    Participants who achieved HbA1c less than or equal to 6.5% (American Association of Clinical Endocrinologists (AACE) target) (yes/no) at weeks 26, 52 and 78 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  18. Participants Who Achieve Weight Loss ≥5% (Yes/no)

    Time frame · Week 26, week 52, week 78

    Registry description

    Participants who achieved weight loss more than or equal to 5% of their baseline body weight (yes/no) at weeks 26, 52 and 78 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  19. Participants Who Achieve Weight Loss ≥10% (Yes/no)

    Time frame · Week 26, week 52, week 78

    Registry description

    Participants who achieved weight loss more than or equal to 10% of their baseline body weight (yes/no) at weeks 26, 52 and 78 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

  20. Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no)

    Time frame · Week 26, week 52, week 78

    Registry description

    Participants who achieved HbA1c less than 7.0 % without severe or blood glucose (BG) confirmed symptomatic hypoglycaemia and without weight gain (yes/no) at weeks 26, 52 and 78 are presented. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia was defined as an episode with plasma glucose value \<3.1 mmol/L with symptoms consistent with hypoglycaemia. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMean· Week 0, week 26

Change in HbA1c: Week 26

GroupValue (Percentage of HbA1c)Spread
Oral Semaglutide 3 mg-0.61.0
Oral Semaglutide 7 mg-1.11.1
Oral Semaglutide 14 mg-1.31.0
Sitagliptin 100 mg-0.80.9
Secondary and other outcome results(7)
Secondary outcomeMean· Week 0, week 26

Change in Body Weight: Week 26

GroupValue (Kg)Spread
Oral Semaglutide 3 mg-1.23.2
Oral Semaglutide 7 mg-2.23.9
Oral Semaglutide 14 mg-3.13.8
Sitagliptin 100 mg-0.63.2
Secondary outcomeMean· Week 0, week 52, week 78

Change in HbA1c: Weeks 52 and 78

GroupValue (Percentage of HbA1c)Spread
Oral Semaglutide 3 mg-0.61.1
Oral Semaglutide 7 mg-1.01.2
Oral Semaglutide 14 mg-1.21.1
Sitagliptin 100 mg-0.71.1
Secondary outcomeMean· Week 0, week 52, week 78

Change in Body Weight (kg): Weeks 52 and 78

GroupValue (Kg)Spread
Oral Semaglutide 3 mg-1.64.1
Oral Semaglutide 7 mg-2.54.9
Oral Semaglutide 14 mg-3.54.7
Sitagliptin 100 mg-0.73.7
Secondary outcomeMean· Week 0, week 26, week 52, week 78

Change in Body Weight (%)

GroupValue (Percentage change)Spread
Oral Semaglutide 3 mg-1.233.57
Oral Semaglutide 7 mg-2.364.09
Oral Semaglutide 14 mg-3.444.21
Sitagliptin 100 mg-0.643.38
Secondary outcomeMean· Week 0, week 26, week 52, week 78

Change in FPG

GroupValue (mmol/L)Spread
Oral Semaglutide 3 mg-0.832.69
Oral Semaglutide 7 mg-1.172.54
Oral Semaglutide 14 mg-1.672.60
Sitagliptin 100 mg-0.902.32
Secondary outcomeMean· Week 0, week 26, week 52, week 78

Change in BMI

GroupValue (Kg/m^2)Spread
Oral Semaglutide 3 mg-0.41.2
Oral Semaglutide 7 mg-0.81.4
Oral Semaglutide 14 mg-1.11.4
Sitagliptin 100 mg-0.21.1
Secondary outcomeMean· Week 0, week 26, week 52, week 78

Change in Waist Circumference

GroupValue (cm)Spread
Oral Semaglutide 3 mg-0.75.0
Oral Semaglutide 7 mg-1.85.2
Oral Semaglutide 14 mg-2.35.2
Sitagliptin 100 mg-0.64.4

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Oral Semaglutide 3 mgParticipants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.5 / 46664 / 466222 / 466
Oral Semaglutide 7 mgParticipants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.4 / 46447 / 464234 / 464
Oral Semaglutide 14 mgParticipants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.1 / 46544 / 465232 / 465
Sitagliptin 100 mgParticipants were to take sitagliptin 100 mg tablets once daily from week 0 to week 78. In addition, participants were to take oral semaglutide placebo tablets once daily from week 0 to week 78.3 / 46658 / 466239 / 466

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies9

Studies that cite this trial.

Studies with results

2 studies on this page

Indexing hint: Randomized controlled trial · 2021

10 results

Efficacy and safety of oral semaglutide in Japanese patients with type 2 diabetes: A post hoc subgroup analysis of the PIONEER 1, 3, 4 and 8 trials.

Araki et al. 2021Diabetes, obesity & metabolismcited by 9

PMID 34472698PMC9293331DOI 10.1111/dom.14536PUB-34472698

Free to read · publisher termsCC BY-NC10 results
Read at sourceSee results (10)

Indexing hint: Randomized controlled trial · 2019

10 results

Effect of Additional Oral Semaglutide vs Sitagliptin on Glycated Hemoglobin in Adults With Type 2 Diabetes Uncontrolled With Metformin Alone or With Sulfonylurea: The PIONEER 3 Randomized Clinical Trial.

Rosenstock et al. 2019JAMAcited by 331

PMID 30903796PMC6484814DOI 10.1001/jama.2019.2942PUB-30903796

Rights unknown10 results
Source linkSee results (10)

More studies

7 studies on this page

PubMed tag: none · 2023

Cost-Effectiveness of Semaglutide vs. Empagliflozin, Canagliflozin, and Sitagliptin for Treatment of Patients with Type 2 Diabetes in Denmark: A Decision-Analytic Modelling Study.

Pulleyblank et al. 2023PharmacoEconomics - opencited by 1

PMID 37178435PMC10333151DOI 10.1007/s41669-023-00416-zPUB-37178435

Free to read · publisher termsCC BY-NC
Read at source

PubMed tag: none · 2022

Long-Term Cost Effectiveness of Oral Semaglutide Versus Empagliflozin and Sitagliptin for the Treatment of Type 2 Diabetes in the Swedish Setting.

Eliasson et al. 2022PharmacoEconomics - opencited by 9

PMID 35064550PMC9043066DOI 10.1007/s41669-021-00317-zPUB-35064550

Free to read · publisher termsCC BY-NC
Read at source

PubMed tag: none · 2022

Efficacy and safety of oral semaglutide by subgroups of patient characteristics in the PIONEER phase 3 programme.

Aroda et al. 2022Diabetes, obesity & metabolismcited by 32

PMID 35373893PMC9321749DOI 10.1111/dom.14710PUB-35373893

Free to read · publisher termsCC BY-NC
Read at source

PubMed tag: none · 2021

Oral Semaglutide Reduces HbA1c and Body Weight in Patients with Type 2 Diabetes Regardless of Background Glucose-Lowering Medication: PIONEER Subgroup Analyses.

Pratley et al. 2021Diabetes therapy : research, treatment and education of diabetes and related disorderscited by 10

PMID 33660198PMC7994454DOI 10.1007/s13300-020-00994-9PUB-33660198

Free to read · publisher termsCC BY-NC
Read at source

PubMed tag: none · 2020

Semaglutide (SUSTAIN and PIONEER) reduces cardiovascular events in type 2 diabetes across varying cardiovascular risk.

Husain et al. 2020Diabetes, obesity & metabolismcited by 154

PMID 31903692PMC7064975DOI 10.1111/dom.13955PUB-31903692

Free to read · publisher termsCC BY-NC
Read at source

Indexing hint: Review · 2020

Efficacy, safety and cardiovascular outcomes of once-daily oral semaglutide in patients with type 2 diabetes: The PIONEER programme.

Thethi et al. 2020Diabetes, obesity & metabolismcited by 98

PMID 32267058PMC7384149DOI 10.1111/dom.14054PUB-32267058

Free to read · publisher termsCC BY-NC
Read at source

PubMed tag: none · 2020

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 et al. 2020Cardiovascular diabetologycited by 33

PMID 32998732PMC7526237DOI 10.1186/s12933-020-01106-4PUB-32998732

CC BY
Download PDF

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: * Male or female, age at least 18 years at the time of signing informed consent For Japan only: Male or female, age at least 20 years at the time of signing informed consent * Diagnosed with T2DM (type 2 diabetes mellitus) for at least 90 days prior to day of screening * HbA1c (glycosylated haemoglobin) 7.0-10.5 % (53-91 mmol/mol) (both inclusive). * Stable daily dose of metformin (equal or above 1500 mg or maximum tolerated dose as documented in subject medical record) alone or in combination with SU (= half of the maximum approved dose according to local label or maximum tolerated dose as documented in subject medical record) within 90 days prior to the day of screening Exclusion Criteria: * Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using adequate contraceptive methods (adequate contraceptive measures as required by local regulation or practice). For certain specific countries: Additional specific requirements apply * Family or personal history of Multiple Endocrine Neoplasia Type 2 (MEN 2) or Medullary Thyroid Carcinoma (MTC) * History of pancreatitis (acute or chronic) * History of major surgical procedures involving the stomach potentially affecting absorption of trial product (e.g. subtotal and total gastrectomy, sleeve gastrectomy, gastric bypass surgery) * Any of the following: myocardial infarction, stroke or hospitalization for unstable angina and/or transient ischaemic attack within the past 180 days prior to the day of screening * Subjects presently classified as being in New York Heart Association (NYHA) Class IV. * Planned coronary, carotid or peripheral artery revascularisation known on the day of screening. * Renal impairment defined as estimated Glomerular Filtration Rate (eGFR) below 60 mL/min/1.73 m\^2 as per Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) * History or presence of malignant neoplasms within the last 5 years (except basal and squamous cell skin cancer and in-situ carcinomas)

PepBank is a research reference. Talk to a doctor before you use any peptide.