Primary outcomeMean· Week 0, week 26
Change in HbA1c
| Group | Value (Percentage of HbA1c) | Spread |
|---|---|---|
| Oral Semaglutide 3 mg | -0.9 | 1.2 |
| Oral Semaglutide 7 mg | -1.3 | 1.0 |
| Oral Semaglutide 14 mg | -1.5 | 1.0 |
| Placebo | -0.3 | 1.2 |
Trial · Interventional
CompletedPhase 3Results postedRegistry dataEfficacy and Safety of Oral Semaglutide Versus Placebo in Subjects With Type 2 Diabetes Mellitus Treated With Diet and Exercise Only
Short name PIONEER 1
NCTNCT02906930 (opens ClinicalTrials.gov in a new tab)Other idNN9924-4233Other id2015-005622-19Other idU1111-1177-5112Other idJapicCTI-163384
Overview
- Status
- Completed
- Phase
- Phase 3
- Enrollment
- 703 participants (actual)
- Sponsor
- Novo Nordisk A/S · Industry
- Design
- Randomized · Double masking
- Countries
11 countries
United States, Algeria, Bulgaria, Czechia, Italy, Japan, Mexico, Romania, Russia, Serbia, Turkey (Türkiye)
- Start
- 20 Sept 2016
- Primary completion
- 30 Oct 2017
- Completion
- 8 Dec 2017
- First posted
- 20 Sept 2016 (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
201620172018
- Ph 3
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 this trial is to investigate efficacy and safety of oral semaglutide versus placebo in subjects with type 2 diabetes mellitus treated with diet and exercise only.
Interventions
- semaglutideDrug
- placeboDrug
Arms4
Experimental
3 mg oral semaglutide
Experimental
7 mg oral semaglutide
Experimental
14 mg oral semaglutide
Placebo comparator
Placebo
Primary outcomes1
Outcomes the sponsor listed as primary.
Change in HbA1c
Time frame · Week 0, week 26
Registry description
Change from baseline (week 0) to week 26 in glycosylated haemoglobin (HbA1c). The endpoint was evaluated based on data from the in-trial observation period. The in-trial observation period - time period from when a subject was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. The primary endpoint was also analysed based on data from the on-treatment without rescue medication observation period. The on-treatment without rescue medication observation period - time period when a subject was on treatment with trial product, excluding any period after initiation of rescue medication.
Secondary outcomes(20)
Change in Body Weight (kg)
Time frame · Week 0, week 26
Registry description
Change from baseline (week 0) to week 26 in body weight. The endpoint was evaluated based on data from the in-trial observation period. The in-trial observation period - time period from when a subject was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. The primary endpoint was also analysed based on data from the on-treatment without rescue medication observation period. The on-treatment without rescue medication observation period - time period when a subject was on treatment with trial product, excluding any period after initiation of rescue medication.
Change in Fasting Plasma Glucose
Time frame · Week 0, week 26
Registry description
Change from baseline (week 0) to week 26 in fasting plasma glucose. The endpoint was evaluated based on data from the in-trial observation period. The in-trial observation period - time period from when a subject was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Change in Mean 7-point SMPG Profile
Time frame · Week 0, week 26
Registry description
Change from baseline (week 0) to week 26 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. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Change in Mean Postprandial Increment Over All Meals in SMPG
Time frame · Week 0, week 26
Registry description
Change from baseline (week 0) to week 26 in the average of the post-prandial increments over all meals. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Change in Fasting Insulin - Ratio to Baseline
Time frame · Week 0, week 26
Registry description
Change from baseline (week 0) to week 26 in fasting insulin (pmol/L) is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product
Change in Fasting Pro-insulin - Ratio to Baseline
Time frame · Week 0, week 26
Registry description
Change from baseline (week 0) to week 26 in fasting pro-insulin (pmol/L) is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product
Change in Fasting Glucagon - Ratio to Baseline
Time frame · Week 0, week 26
Registry description
Change from baseline (week 0) to week 26 in fasting glucagon (pg/mL) is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product
Change in HOMA-IR (Insulin Resistance) - Ratio to Baseline
Time frame · Week 0, week 26
Registry description
Change from baseline (week 0) to week 26 in homeostatic model assessment index of insulin resistance (HOMA-IR) (%) is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Change in HOMA-B (Beta-cell Function) - Ratio to Baseline
Time frame · Week 0, week 26
Registry description
Change from baseline (week 0) to week 26 in homeostatic model assessment index of beta-cell function (HOMA-B) (%) is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Change in CRP - Ratio to Baseline
Time frame · Week 0, week 26
Registry description
Change from baseline (week 0) to week 26 in C-reactive protein (CRP) (mg/L) is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Change in Body Weight (%)
Time frame · Week 0, week 26
Registry description
Change from baseline (week 0) to week 26 in body weight. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Change in BMI
Time frame · Week 0, week 26
Registry description
Change from baseline (week 0) to week 26 in body mass index (BMI). 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 or premature discontinuation of trial product.
Change in Waist Circumference
Time frame · Week 0, week 26
Registry description
Change from baseline (week 0) to week 26 in waist circumference. 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 or premature discontinuation of trial product.
Change in Fasting Total Cholesterol - Ratio to Baseline
Time frame · Week 0, week 26
Registry description
Change from baseline (week 0) to week 26 in fasting total cholesterol (mmol/L) is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Change in Fasting LDL Cholesterol - Ratio to Baseline
Time frame · Week 0, week 26
Registry description
Change from baseline (week 0) to week 26 in fasting low-density lipoprotein (LDL) cholesterol (mmol/L) is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Change in Fasting HDL Cholesterol - Ratio to Baseline
Time frame · Week 0, week 26
Registry description
Change from baseline (week 0) to week 26 in fasting high-density lipoprotein (HDL) cholesterol (mmol/L) is presented as ratio to baseline. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Change in Fasting Triglycerides - Ratio to Baseline
Time frame · Week 0, week 26
Registry description
Change from baseline (week 0) to week 26 in triglycerides (mmol/L) 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 or premature discontinuation of trial product.
Participants Who Achieve HbA1c < 7.0 % (53 mmol/Mol) ADA Target (Yes/no)
Time frame · Week 26
Registry description
Participants who achieved HbA1c \<7.0% (53 mmol/mol) (American Diabetes Association (ADA) target), at week 26 are presented. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Participants Who Achieve HbA1c ≤ 6.5 % (48 mmol/Mol) AACE Target (Yes/no)
Time frame · Week 26
Registry description
Participants who achieved HbA1c ≤6.5% (48 mmol/mol) (American Association of Clinical Endocrinologists (AACE) target), at week 26 are presented. The results are based on the data from the in-trial observation period. In trial observation period: the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product.
Participants Who Achieve Body Weight Loss ≥ 5 % (Yes/no)
Time frame · Week 26
Registry description
Participants who achieved body weight loss more than or equal to 5% of their baseline body weight (yes/no) at week 26 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 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
Secondary and other outcome results(7)
Secondary outcomeMean· Week 0, week 26
Change in Body Weight (kg)
| Group | Value (kg) | Spread |
|---|---|---|
| Oral Semaglutide 3 mg | -1.5 | 3.3 |
| Oral Semaglutide 7 mg | -2.6 | 4.1 |
| Oral Semaglutide 14 mg | -4.0 | 4.2 |
| Placebo | -1.4 | 3.5 |
Secondary outcomeMean· Week 0, week 26
Change in Fasting Plasma Glucose
| Group | Value (mmol/L) | Spread |
|---|---|---|
| Oral Semaglutide 3 mg | -0.89 | 2.67 |
| Oral Semaglutide 7 mg | -1.52 | 2.28 |
| Oral Semaglutide 14 mg | -1.92 | 2.04 |
| Placebo | -0.18 | 2.37 |
Secondary outcomeMean· Week 0, week 26
Change in Mean 7-point SMPG Profile
| Group | Value (mmol/L) | Spread |
|---|---|---|
| Oral Semaglutide 3 mg | -1.8 | 2.3 |
| Oral Semaglutide 7 mg | -2.1 | 2.0 |
| Oral Semaglutide 14 mg | -2.3 | 2.4 |
| Placebo | -0.5 | 2.6 |
Secondary outcomeMean· Week 0, week 26
Change in Mean Postprandial Increment Over All Meals in SMPG
| Group | Value (mmol/L) | Spread |
|---|---|---|
| Oral Semaglutide 3 mg | -0.4 | 2.3 |
| Oral Semaglutide 7 mg | -0.8 | 2.0 |
| Oral Semaglutide 14 mg | -1.2 | 2.1 |
| Placebo | -0.3 | 2.0 |
Secondary outcomeGeometric mean· Week 0, week 26
Change in Fasting Insulin - Ratio to Baseline
| Group | Value (Ratio of fasting insulin) | Spread |
|---|---|---|
| Oral Semaglutide 3 mg | 1.12 | 59.2 |
| Oral Semaglutide 7 mg | 1.07 | 49.2 |
| Oral Semaglutide 14 mg | 0.98 | 45.0 |
| Placebo | 0.97 | 59.2 |
Secondary outcomeGeometric mean· Week 0, week 26
Change in Fasting Pro-insulin - Ratio to Baseline
| Group | Value (Ratio of fasting pro-insulin) | Spread |
|---|---|---|
| Oral Semaglutide 3 mg | 0.84 | 71.5 |
| Oral Semaglutide 7 mg | 0.74 | 74.3 |
| Oral Semaglutide 14 mg | 0.62 | 75.5 |
| Placebo | 0.89 | 76.5 |
Secondary outcomeGeometric mean· Week 0, week 26
Change in Fasting Glucagon - Ratio to Baseline
| Group | Value (Ratio of fasting glucagon) | Spread |
|---|---|---|
| Oral Semaglutide 3 mg | 1.00 | 28.2 |
| Oral Semaglutide 7 mg | 0.90 | 27.1 |
| Oral Semaglutide 14 mg | 0.89 | 25.7 |
| Placebo | 0.95 | 25.4 |
Adverse events, as posted
| Group | Deaths | Serious events | Other events |
|---|---|---|---|
| Oral Semaglutide 3 mgParticipants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 26. | 0 / 175 | 5 / 175 | 48 / 175 |
| Oral Semaglutide 7 mgParticipants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 26. | 0 / 175 | 3 / 175 | 37 / 175 |
| Oral Semaglutide 14 mgParticipants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26. | 1 / 175 | 2 / 175 | 45 / 175 |
| PlaceboParticipants were to take placebo tablets once daily for a period of 26 weeks. | 0 / 178 | 8 / 178 | 26 / 178 |
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
1 study 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
Indexing hint: Randomized controlled trial · 2019
Validation of a new measure of quality of life in obesity trials: Impact of Weight on Quality of Life-Lite Clinical Trials Version.
Kolotkin et al. 2019Clinical obesitycited by 59
PMID 30993900PMC6593657DOI 10.1111/cob.12310PUB-30993900
Free to read · publisher termsCC BY-NC
More studies
7 studies on this page
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
PubMed tag: none · 2022
Impact of semaglutide on high-sensitivity C-reactive protein: exploratory patient-level analyses of SUSTAIN and PIONEER randomized clinical trials.
Mosenzon et al. 2022Cardiovascular diabetologycited by 65
PMID 36056351PMC9440529DOI 10.1186/s12933-022-01585-7PUB-36056351
CC BY
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
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
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
Indexing hint: Review · 2019
Incorporating and interpreting regulatory guidance on estimands in diabetes clinical trials: The PIONEER 1 randomized clinical trial as an example.
Aroda et al. 2019Diabetes, obesity & metabolismcited by 59
PMID 31168921PMC6771751DOI 10.1111/dom.13804PUB-31168921
Free to read · publisher termsCC BY-NC
PubMed tag: none · 2019
PIONEER 1: Randomized Clinical Trial of the Efficacy and Safety of Oral Semaglutide Monotherapy in Comparison With Placebo in Patients With Type 2 Diabetes.
Aroda et al. 2019Diabetes carecited by 388
PMID 31186300DOI 10.2337/dc19-0749PUB-31186300
Full text at the publisher
Other registry references
References listed at the registry that are not in PepBank. They link to PubMed.
- ResultGorst-Rasmussen A, Tarp-Johansen MJ. Fast tipping point sensitivity analyses in clinical trials with missing continuous outcomes under multiple imputation. J Biopharm Stat. 2022 Nov 2;32(6):942-953. doi: 10.1080/10543406.2022.2058525. Epub 2022 Jun 2. PMID 35653556
Eligibility
Who could join, as posted.
- Sex
- All
- Age
- from 18 Years
- Healthy volunteers
- Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: - Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial - Male or female, age above or equal to 18 years at the time of signing informed consent.For Japan only: Male or female, age above or equal to 20 years at the time of signing informed consent. For Algeria only: Male or female, age above or equal to 19 years at the time of signing informed consent - Diagnosed with type 2 diabetes mellitus for at least 30 days prior to day of screening - HbA1c (glycosylated haemoglobin) between 7.0-9.5% (53-80 mmol/mol) (both inclusive) - Treatment with diet and exercise for at least 30 days prior to 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 an adequate contraceptive method (adequate contraceptive measure as required by local regulation or practice) For Japan only: Adequate contraceptive measures are abstinence (not having sex), diaphragm, condom (by the partner), intrauterine device, sponge, spermicide or oral contraceptives.For Czech Republic only: Adequate contraceptive measures are always one highly reliable method (such as intrauterine device, sterilisation of one of the partners, hormonal birth control methods) plus one supplementary barrier method (such as condom, diaphragm) with a spermicide. In justified cases, this combination may be replaced with a double-barrier method with a spermicide. Total sexual abstinence may also be considered contraception. (Please note: hormonal contraception should always be discussed with a gynaecologist) - Any disorder, which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol - Family or personal history of multiple endocrine neoplasia type 2 or medullary thyroid carcinomas - 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 hospitalisation for unstable angina or transient ischaemic attack within the past 180 days prior to the day of screening and randomisation - Subjects presently classified as being in New York Heart Association Class IV. - Planned coronary, carotid or peripheral artery revascularisation known on the day of screening - Subjects with alanine aminotransferase above 2.5 x upper normal limit - Renal impairment defined as estimated glomerular filtration rate below 60 mL/min/1.73 m\^2 as per Chronic Kidney Disease Epidemiology Collaboration formula - Treatment with any medication for the indication of diabetes or obesity in a period of 90 days before the day of screening. An exception is short-term insulin treatment for acute illness for a total of below or equal to 14 days - Proliferative retinopathy or maculopathy requiring acute treatment. Verified by fundus photography or dilated fundoscopy performed within 90 days prior to randomisation - History or presence of malignant neoplasms within the last 5 years (except basal and squamous cell skin cancer and in-situ carcinomas)
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