Primary outcomeMean· Week 0, week 26
Change in HbA1c (Week 26)
| Group | Value (Percentage of HbA1c) | Spread |
|---|---|---|
| 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 |
Trial · Interventional
CompletedPhase 3Results postedRegistry dataEfficacy and Safety of Oral Semaglutide Versus Placebo in Subjects With Type 2 Diabetes Mellitus Treated With Insulin
Short name PIONEER 8
NCTNCT03021187 (opens ClinicalTrials.gov in a new tab)Other idNN9924-4280Other id2016-000988-16Other idU1111-1180-3637Other idJapicCTI-173508
Overview
- Status
- Completed
- Phase
- Phase 3
- Enrollment
- 731 participants (actual)
- Sponsor
- Novo Nordisk A/S · Industry
- Design
- Randomized · Double masking
- Countries
10 countries
United States, Canada, France, Greece, India, Japan, Mexico, Poland, Puerto Rico, Russia
- Start
- 2 Feb 2017
- Primary completion
- 18 Jan 2018
- Completion
- 22 Aug 2018
- First posted
- 13 Jan 2017 (estimated)
- Last update posted
- 2 Mar 2020
- 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
201720182019
- 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 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.
Interventions
- semaglutideDrug
- semaglutideDrug
- semaglutideDrug
- placeboDrug
Arms4
Experimental
Semaglutide 3 mg
Experimental
Semaglutide 3 mg + 7 mg
Experimental
Semaglutide 3 mg + 7 mg + 14 mg
Placebo comparator
Placebo
Primary outcomes1
Outcomes the sponsor listed as primary.
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 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 period after initiation of rescue medication, if any, and excludes the period after premature trial discontinuation, if any.
Secondary outcomes(20)
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 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 discontinuation, if any.
Change in HbA1c (Week 52)
Time frame · Week 0, week 52
Registry description
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.
Change in Body Weight (kg) (Week 52)
Time frame · Week 0, week 52
Registry description
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.
Change in Fasting Plasma Glucose (FPG)
Time frame · Week 0, week 26, week 52
Registry description
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.
Change in Self-measured Plasma Glucose (SMPG) Mean 7-point Profile
Time frame · Week 0, week 26, week 52
Registry description
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 randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any.
Change in SMPG Mean Postprandial Increment Over All Meals
Time frame · Week 0, week 26, week 52
Registry description
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.
Change in Body Weight (Percentage)
Time frame · Week 0, week 26, week 52
Registry description
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.
Change in Body Mass Index
Time frame · Week 0, week 26, week 52
Registry description
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.
Change in Waist Circumference
Time frame · Week 0, week 26, week 52
Registry description
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.
Change in Total Cholesterol - Ratio to Baseline
Time frame · Week 0, week 26, week 52
Registry description
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.
Change in LDL Cholesterol - Ratio to Baseline
Time frame · Week 0, week 26, week 52
Registry description
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.
Change in HDL Cholesterol - Ratio to Baseline
Time frame · Week 0, week 26, week 52
Registry description
Change from baseline (week 0) in HDL cholesterol (mmol/L) at weeks 26 and 52 is presented as ratio to baseline. 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.
Change in Triglycerides - Ratio to Baseline
Time frame · Week 0, week 26, week 52
Registry description
Change from baseline (week 0) in triglycerides (mmol/L) at weeks 26 and 52 is presented as ratio to baseline. 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.
Change in Total Daily Insulin Dose
Time frame · Week 0, week 26, week 52
Registry description
Change from baseline in total daily insulin dose to week 26 and week 52 is presented. 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.
Participants Who Achieve: HbA1c < 7.0% (53 mmol/Mol) (American Diabetes Association (ADA) Target) (Yes/no)
Time frame · Week 26, week 52
Registry description
Number of particpants achieving HbA1c \< 7.0 % (53 mmol/mol) according to American Diabetes Association (ADA) target, at 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.
Participants Who Achieve: HbA1c ≤ 6.5% (48 mmol/Mol) (AACE Target) (Yes/no)
Time frame · Week 26, week 52
Registry description
Number of participants achieving HbA1c ≤ 6.5% (48 mmol/mol) according to American Association of Clinical Endocrinologists (AACE) target, at 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.
Participants Who Achieve Body Weight Loss ≥5% (Yes/no)
Time frame · Week 26, week 52
Registry description
Participants who achieved weight loss more than or equal to 5% of their baseline body weight (yes/no) at weeks 26 and 52 are presented. 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.
Participants Who Achieve Body Weight Loss ≥10% (Yes/no)
Time frame · Week 26, week 52
Registry description
Participants who achieved weight loss more than or equal to 10% of their baseline body weight (yes/no) at weeks 26 and 52 are presented. 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. Results are based on the data from the in-trial observation period, which started at the date of randomisation and included the period after initiatiion of of rescue medication and/or premature trial product discontinuation, if any.
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
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 and 52 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.
Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no)
Time frame · Week 26, week 52
Registry description
Participants who achieved HbA1c reduction more than or equal to 1% of their baseline HbA1c and weight loss of more than or equal to 3% of their baseline body weight (yes/no) at weeks 26 and 52 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.
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 (Week 26)
| Group | Value (Kg) | Spread |
|---|---|---|
| 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 |
Secondary outcomeMean· Week 0, week 52
Change in HbA1c (Week 52)
| Group | Value (Percentage of HbA1c) | Spread |
|---|---|---|
| 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 |
Secondary outcomeMean· Week 0, week 52
Change in Body Weight (kg) (Week 52)
| Group | Value (Kg) | Spread |
|---|---|---|
| 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 |
Secondary outcomeMean· Week 0, week 26, week 52
Change in Fasting Plasma Glucose (FPG)
| Group | Value (mmol/L) | Spread |
|---|---|---|
| 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 |
Secondary outcomeMean· Week 0, week 26, week 52
Change in Self-measured Plasma Glucose (SMPG) Mean 7-point Profile
| Group | Value (mmol/L) | Spread |
|---|---|---|
| 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 |
Secondary outcomeMean· Week 0, week 26, week 52
Change in SMPG Mean Postprandial Increment Over All Meals
| Group | Value (mmol/L) | Spread |
|---|---|---|
| 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 |
Secondary outcomeMean· Week 0, week 26, week 52
Change in Body Weight (Percentage)
| Group | Value (Percentage change) | Spread |
|---|---|---|
| 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 |
Adverse events, as posted
| Group | Deaths | Serious events | Other events |
|---|---|---|---|
| Oral Semaglutide 3 mgSubjects were to take oral semaglutide 3 mg tablets once daily from week 1 to 52. | 0 / 184 | 25 / 184 | 77 / 184 |
| Oral Semaglutide 7 mgSubjects were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 52: 3 mg from week 1 to 4 and 7 mg from week 5 to 52. | 0 / 181 | 19 / 181 | 86 / 181 |
| Oral Semaglutide 14 mgSubjects were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 52: 3 mg from week 1 to 4, 7 mg from week 5 to 8 and 14 mg from week 9 to 52. | 3 / 181 | 12 / 181 | 100 / 181 |
| PlaceboParticipants were to take oral semaglutide placebo tablets once-daily for a period of 52 weeks. | 0 / 184 | 17 / 184 | 73 / 184 |
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
Studies5
Studies that cite this trial.
Studies with results
1 study on this page
Indexing hint: Randomized controlled trial · 2019
9 results
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 et al. 2019Diabetes carecited by 222
PMID 31530667PMC7364672DOI 10.2337/dc19-0898PUB-31530667
Rights unknown9 results
More studies
4 studies on this page
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
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
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. - Diagnosed with type 2 diabetes mellitus 90 days or more prior to the day of screening. - HbA1c (glycosylated haemoglobin) of 7.0-9.5% (53-80 mmol/mol) (both inclusive). - Stable treatment with one of the following insulin regimens (minimum 10 IU/day) 90 or more days prior to the day of screening. Maximum 20% change in total daily dose is acceptable: (1) Basal insulin alone or (2) Basal and bolus insulin in any combination or (3) Premixed insulin including combinations of soluble insulins 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 Greece only: adequate contraceptive measures are defined as combined hormonal contraception (containing oestrogen and progesterone), which suppress ovulation (oral, intravaginal, percutaneous), progesterone-only hormonal contraception which suppress ovulation (oral, injectable, implantable), intrauterine device, hormone-releasing intrauterine system, bilateral tubal occlusion, partner with vasectomy, sexual abstinence. For Japan only: Adequate contraceptive measures are abstinence (not having sex), diaphragm, condom (by the partner), intrauterine device, sponge, spermicide or oral contraceptives. For Canada only: adequate contraceptive measures are defined as combined hormonal contraception (containing oestrogen and progesterone), which suppress ovulation (oral, intravaginal, percutaneous), progesterone-only hormonal contraception which suppress ovulation (oral, injectable, implantable), intrauterine device, hormone-releasing intrauterine system, bilateral tubal occlusion, partner with vasectomy, sexual abstinence - 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 (MEN 2) or Medullary Thyroid Carcinoma (MTC). - History of pancreatitis (acute or chronic). - History of major surgical procedures involving the stomach and potentially affecting absorption of trial product (e.g. subtotal and total gastrectomy, sleeve gastrectomy, gastric bypass surgery). - Any of the following: myocardial infarction (MI), stroke or hospitalisation for unstable angina or transient ischaemic attack within the past 180 days prior to the day of screening and randomisation. - 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) less than 60 mL/min/1.73 m\^2 as per Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI). - Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria in a period of 90 days before the day of screening. An exception is short-term change of insulin treatment for acute illness for a total of 14 days or less. - Known hypoglycaemic unawareness according to Clarke's questionnaire. - 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 carcinoma in situ). - Subjects with alanine aminotransferase (ALT) more than 2.5 x upper normal limit (UNL).
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