Primary outcomeMean· Week 0, week 26
Change in HbA1c (Week 26)
| Group | Value (Percentage point of HbA1c) | Spread |
|---|---|---|
| Oral Semaglutide 3 mg | -1.1 | 0.8 |
| Oral Semaglutide 7 mg | -1.7 | 0.8 |
| Oral Semaglutide 14 mg | -1.7 | 0.8 |
| Liraglutide 0.9 mg | -1.4 | 1.1 |
| Placebo | -0.2 | 0.7 |
Trial · Interventional
CompletedPhase 3Results postedRegistry dataDose-response, Safety and Efficacy of Oral Semaglutide Versus Placebo and Versus Liraglutide, All as Monotherapy in Japanese Subjects With Type 2 Diabetes
Short name PIONEER 9
NCTNCT03018028 (opens ClinicalTrials.gov in a new tab)Other idNN9924-4281Other idU1111-1181-4048Other idJapicCTI-173489
Overview
- Status
- Completed
- Phase
- Phase 3
- Enrollment
- 243 participants (actual)
- Sponsor
- Novo Nordisk A/S · Industry
- Design
- Randomized · Double masking
- Countries
1 country
Japan
- Start
- 10 Jan 2017
- Primary completion
- 9 Jan 2018
- Completion
- 15 Aug 2018
- First posted
- 11 Jan 2017 (estimated)
- Last update posted
- 15 Jan 2021
- 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 in Asia. The aim of this trial is to investigate the dose-response relationship of once-daily dosing of three dose levels (3, 7 and 14 mg) of oral semaglutide versus placebo as monotherapy on glycaemic control in Japanese subjects with type 2 diabetes mellitus
Interventions
- SemaglutideDrug
- PlaceboDrug
- LiraglutideDrug
Arms5
Experimental
Oral semaglutide 3 mg
Experimental
Oral semaglutide 7 mg
Experimental
Oral semaglutide 14 mg
Placebo comparator
Oral placebo
Active comparator
Liraglutide 0.9 mg
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) to week 26 in glycosylated haemoglobin (HbA1c). The endpoint was analysed based on data from the on-treatment without rescue medication observation period. On-treatment without rescue medication observation period - time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication. The endpoint was also evaluated based on data from the in-trial observation period. In-trial observation period - 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.
Secondary outcomes(20)
Change in HbA1c (Week 52)
Time frame · Week 0, week 52
Registry description
Change from baseline (week 0) to week 52 in HbA1c. Data based on on-treatment without rescue medication observation period is presented. The on-treatment without rescue medication observation period - time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication.
Change in Body Weight (kg)
Time frame · Week 0, week 26, week 52
Registry description
Change from baseline (week 0) in body weight. Data based on on-treatment without rescue medication observation period is presented. The on-treatment without rescue medication observation period - time period when a participant 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, week 52
Registry description
Change from baseline (week 0) in fasting plasma glucose. Data based on on-treatment without rescue medication observation period is presented. The on-treatment without rescue medication observation period - time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication.
Change in Self-measured Plasma Glucose 7-point Profile (SMPG) - Mean 7-point Profile
Time frame · Week 0, week 26, week 52
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. Data based on on-treatment without rescue medication observation period is presented. The on-treatment without rescue medication observation period - time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication.
Change in Mean Postprandial Increment Over All Meals in SMPG
Time frame · Week 0, week 26 and week 52
Registry description
Change from baseline (week 0) in the average of the post-prandial increments over all meals. Data based on on-treatment without rescue medication observation period is presented. The on-treatment without rescue medication observation period - time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication.
Change in Body Weight (%)
Time frame · Week 0, week 26 and week 52
Registry description
Relative change (%) from baseline (week 0) in body weight (kg). Data based on on-treatment without resue medication observation period is presented. The on-treatment without rescue medication observation period - time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication.
Change in Body Mass Index
Time frame · Week 0, week 26 and week 52
Registry description
Change from baseline (week 0) in body mass index (BMI). BMI was calculated based on body weight and height based on the formulae: BMI kg/m\^2 = body weight (kg)/(Height (m) x Height (m)). Data based on on-treatment without rescue medication observation period is presented. The on-treatment without rescue medication observation period - time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication.
Change in Waist Circumference
Time frame · Week 0, week 26 and week 52
Registry description
Change from baseline (week 0) in waist circumference. Data based on on-treatment without rescue medication observation period is presented. The on-treatment without rescue medication observation period - time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication.
Change in Total Cholesterol (Ratio to Baseline)
Time frame · Week 0, week 26 and week 52
Registry description
Change from baseline (week 0) in total cholesterol (measured as mmol/L) is presented as ratio to baseline. Data based on on-treatment without rescue medication observation period is presented. The on-treatment without rescue medication observation period - time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication.
Change in HDL Cholesterol (Ratio to Baseline)
Time frame · Week 0, week 26 and week 52
Registry description
Change from baseline (week 0) in high density lipoprotein (HDL) cholesterol (measured as mmol/L) is presented as ratio to baseline. Data based on on-treatment without rescue medication observation period is presented. The on-treatment without rescue medication observation period - time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication.
Change in LDL Cholesterol (Ratio to Baseline)
Time frame · Week 0, week 26 and week 52
Registry description
Change from baseline (week 0) in low density lipoprotein (LDL) cholesterol (measured as mmol/L) is presented as ratio to baseline. Data based on on-treatment without rescue medication observation period is presented. The on-treatment without rescue medication observation period - time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication.
Change in VLDL Cholesterol (Ratio to Baseline)
Time frame · Week 0, week 26 and week 52
Registry description
Change from baseline (week 0) in very low density lipoprotein (VLDL) cholesterol (measured as mmol/L) is presented as ratio to baseline. Data based on on-treatment without rescue medication observation period is presented. The on-treatment without rescue medication observation period - time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication.
Change in Triglycerides (Ratio to Baseline)
Time frame · Week 0, week 26 and week 52
Registry description
Change from baseline (week 0) in triglycerides (measured as mmol/L) is presented as ratio to baseline. Data based on on-treatment without rescue medication observation period is presented. The on-treatment without rescue medication observation period - time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication.
Change in Fasting Insulin (Ratio to Baseline)
Time frame · Week 0, week 26 and week 52
Registry description
Change from baseline (week 0) in fasting insulin (measured as picomoles per liter \[pmol/L\]) is presented as ratio to baseline. Data based on on-treatment without rescue medication observation period is presented. The on-treatment without rescue medication observation period - time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication.
Change in Fasting C-peptide (Ratio to Baseline)
Time frame · Week 0, week 26 and week 52
Registry description
Change from baseline (week 0) in fasting C-peptide (measured as nanomoles per liter \[nmol/L\]) is presented as ratio to baseline. Data based on on-treatment without rescue medication observation period is presented. The on-treatment without rescue medication observation period - time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication.
Change in Fasting Glucagon (Ratio to Baseline)
Time frame · Week 0, week 26 and week 52
Registry description
Change from baseline (week 0) in fasting glucagon (measured as picograms per milliliter \[pg/mL\]) is presented as ratio to baseline. Data based on on-treatment without rescue medication observation period is presented. The on-treatment without rescue medication observation period - time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication.
Change in Fasting Pro-insulin (Ratio to Baseline)
Time frame · Week 0, week 26 and week 52
Registry description
Change from baseline (week 0) in fasting pro-insulin (measured as pmol/L) is presented as ratio to baseline. Data based on on-treatment without rescue medication observation period is presented. The on-treatment without rescue medication observation period - time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication.
Change in Fasting Pro-insulin/Insulin Ratio (Ratio to Baseline)
Time frame · Week 0, week 26 and week 52
Registry description
Change from baseline (week 0) in fasting pro-insulin/insulin ratio is presented as ratio to baseline. Data based on on-treatment without rescue medication observation period is presented. The on-treatment without rescue medication observation period - time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication.
Change in Insulin Resistance (HOMA-IR) (Ratio to Baseline)
Time frame · Week 0, week 26 and week 52
Registry description
Change from baseline (week 0) in insulin resistance (measured as percentage of insulin resistance) by homeostatic model assessment index of insulin resistance (HOMA-IR) is presented as ratio to baseline. Data based on on-treatment without rescue medication observation period is presented. The on-treatment without rescue medication observation period - time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication.
Change in Beta-cell Function (HOMA-B) (Ratio to Baseline)
Time frame · Week 0, week 26 and week 52
Registry description
Change from baseline (week 0) in beta-cell function (measured as percentage of beta-cell function) by homeostatic model assessment index of beta-cell function is presented as ratio to baseline. Data based on on-treatment without rescue medication observation period is presented. The on-treatment without rescue medication observation period - time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication.
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 52
Change in HbA1c (Week 52)
| Group | Value (Percentage of HbA1c) | Spread |
|---|---|---|
| Oral Semaglutide 3 mg | -1.0 | 0.9 |
| Oral Semaglutide 7 mg | -1.4 | 0.9 |
| Oral Semaglutide 14 mg | -1.5 | 0.8 |
| Liraglutide 0.9 mg | -1.3 | 1.0 |
| Placebo | 0.1 | 0.7 |
Secondary outcomeMean· Week 0, week 26, week 52
Change in Body Weight (kg)
| Group | Value (Kilogram (kg)) | Spread |
|---|---|---|
| Oral Semaglutide 3 mg | -0.4 | 1.9 |
| Oral Semaglutide 7 mg | -1.2 | 1.9 |
| Oral Semaglutide 14 mg | -2.4 | 3.0 |
| Liraglutide 0.9 mg | 0.1 | 1.6 |
| Placebo | -1.1 | 1.6 |
Secondary outcomeMean· Week 0, week 26, week 52
Change in Fasting Plasma Glucose
| Group | Value (Millimoles per liter (mmol/L)) | Spread |
|---|---|---|
| Oral Semaglutide 3 mg | -1.62 | 1.74 |
| Oral Semaglutide 7 mg | -1.60 | 1.74 |
| Oral Semaglutide 14 mg | -2.37 | 1.84 |
| Liraglutide 0.9 mg | -2.48 | 1.76 |
| Placebo | -0.37 | 1.50 |
Secondary outcomeMean· Week 0, week 26, week 52
Change in Self-measured Plasma Glucose 7-point Profile (SMPG) - Mean 7-point Profile
| Group | Value (mmol/L) | Spread |
|---|---|---|
| Oral Semaglutide 3 mg | -2.2 | 2.2 |
| Oral Semaglutide 7 mg | -2.6 | 1.8 |
| Oral Semaglutide 14 mg | -3.1 | 2.1 |
| Liraglutide 0.9 mg | -2.8 | 2.1 |
| Placebo | -0.8 | 1.7 |
Secondary outcomeMean· Week 0, week 26 and week 52
Change in Mean Postprandial Increment Over All Meals in SMPG
| Group | Value (mmol/L) | Spread |
|---|---|---|
| Oral Semaglutide 3 mg | -0.7 | 2.1 |
| Oral Semaglutide 7 mg | -1.2 | 2.3 |
| Oral Semaglutide 14 mg | -2.0 | 2.3 |
| Liraglutide 0.9 mg | -1.1 | 2.1 |
| Placebo | -0.5 | 2.4 |
Secondary outcomeMean· Week 0, week 26 and week 52
Change in Body Weight (%)
| Group | Value (Percentage change) | Spread |
|---|---|---|
| Oral Semaglutide 3 mg | -0.64 | 2.65 |
| Oral Semaglutide 7 mg | -1.63 | 2.78 |
| Oral Semaglutide 14 mg | -3.54 | 4.33 |
| Liraglutide 0.9 mg | 0.08 | 2.23 |
| Placebo | -1.58 | 2.27 |
Secondary outcomeMean· Week 0, week 26 and week 52
Change in Body Mass Index
| Group | Value (Kilogram per square meter (kg/m^2)) | Spread |
|---|---|---|
| Oral Semaglutide 3 mg | -0.1 | 0.7 |
| Oral Semaglutide 7 mg | -0.4 | 0.7 |
| Oral Semaglutide 14 mg | -0.9 | 1.1 |
| Liraglutide 0.9 mg | 0.0 | 0.6 |
| Placebo | -0.4 | 0.6 |
Adverse events, as posted
| Group | Deaths | Serious events | Other events |
|---|---|---|---|
| Oral Semaglutide 3 mgParticipants received 3.0 mg of oral semaglutide tablets once daily in the morning in fasted state for 52 weeks. The oral semaglutide tablet was taken once daily in a fasting state at least 30 min before the first meal of the day with up to half a glass of water. | 0 / 49 | 2 / 49 | 29 / 49 |
| Oral Semaglutide 7 mgParticipants received oral semaglutide tablets once daily in the morning in fasted state for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 7 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 52). The oral semaglutide tablet was taken once daily in a fasting state at least 30 min before the first meal of the day with up to half a glass of water. | 0 / 49 | 3 / 49 | 21 / 49 |
| Oral Semaglutide 14 mgParticipants received oral semaglutide tablets once daily in the morning in fasted state for 52 weeks. Participants started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52). The oral semaglutide tablet was taken once daily in a fasting state at least 30 min before the first meal of the day with up to half a glass of water. | 0 / 48 | 0 / 48 | 25 / 48 |
| Liraglutide 0.9 mgParticipants received liraglutide for 52 weeks. Liraglutide was administered once-daily as subcutaneous injection (under the skin) in the abdomen, thigh or upper arm and was taken with or without food, preferably at the same time in the morning or evening. Participants initiated liraglutide at 0.3 mg once-daily, and were dose escalated after 1 week to 0.6 mg, and then dose escalated after 1 week to the recommended maximum dose of 0.9 mg. | 0 / 48 | 0 / 48 | 23 / 48 |
| PlaceboParticipants received placebo (for oral semaglutide) tablets once daily for 52 weeks. The placebo tablet was taken once daily in the morning in a fasting state at least 30 min before the first meal of the day with up to half a glass of water. | 0 / 49 | 3 / 49 | 27 / 49 |
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
Studies4
Studies that cite this trial.
Studies with results
1 study on this page
Indexing hint: Randomized controlled trial · 2020
13 results
Dose-response, efficacy, and safety of oral semaglutide monotherapy in Japanese patients with type 2 diabetes (PIONEER 9): a 52-week, phase 2/3a, randomised, controlled trial.
Yamada et al. 2020The lancet. Diabetes & endocrinologycited by 170
PMID 32333875DOI 10.1016/s2213-8587(20)30075-9PUB-32333875
Rights unknown13 results
More studies
3 studies on this page
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 20 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
* Japanese male or female, age above or equal to 20 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 6.5%-9.5% (48-80 mmol/mol) (both inclusive) for subjects treated with oral antidiabetic drug as monotherapy and 7.0%-10.0% (53-86 mmol/mol) (both inclusive) for subjects treated with diet and exercise therapy alone
* Treatment for at least 30 days prior to day of screening with;- stable daily dose of oral anti-diabetic drug as monotherapy (allowed oral anti-diabetic drugs are: metformin, sulphonylurea, glinide, α-glucosidase inhibitor, dipeptidyl peptidase-4 inhibitor and sodium-glucose cotransporter-2 inhibitor) at a half-maximum approved dose or below according to Japanese labelling in addition to diet and exercise therapy. or - diet and exercise therapy alone
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 measures are abstinence (not having sex), diaphragm, condom (by the partner), intrauterine device, sponge, spermicide or oral contraceptives
* 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, stroke or hospitalisation for unstable angina or transient ischaemic attack within the past 180 days prior to the day of screening and randomisation
* Subject 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
* Subjects with alanine aminotransferase (ALT) above 2.5 x upper normal limit (UNL)
* Renal impairment defined as estimated Glomerular Filtration Rate (eGFR) below 30 mL/min/1.73 m\^2 as per Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI)
* Treatment with once-weekly glucagon-like peptide-1 receptor agonist (GLP-1 RA), once weekly dipeptidyl peptidase-4 (DPP-4) inhibitor or thiazolidinedione in a period of 90 days before the day of screening
* Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria in a period of 60 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)
* Initiation of anti-diabetic medication between the day of screening and the day of randomisation
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