Phase 3
Completed N=243
Dose-response, Safety and Efficacy of Oral Semaglutide Versus Placebo and Versus Liraglutide, All as Monotherapy in Japanese Subjects With Type 2 Diabetes
Source: ClinicalTrials.gov NCT03018028 ↗Enrolled (actual)
243
Serious AEs
3.3%
Results posted
Dec 2019
Primary outcomePrimary: Change in HbA1c (Week 26) — -1.1; -1.7; -1.7; -1.4 Percentage point of HbA1c — p=<0.0001
◆ Published Evidence
Highly cited
220citations · ~37 / year
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.
Summary
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
Linked Publications (4)
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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.
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Semaglutide (SUSTAIN and PIONEER) reduces cardiovascular events in type 2 diabetes across varying cardiovascular risk.
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Efficacy, safety and cardiovascular outcomes of once-daily oral semaglutide in patients with type 2 diabetes: The PIONEER programme.
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Effects of semaglutide on risk of cardiovascular events across a continuum of cardiovascular risk: combined post hoc analysis of the SUSTAIN and PIONEER trials.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in HbA1c (Week 26) |
-1.1; -1.7; -1.7; -1.4; -0.2; -1.1 | <0.0001 sig |
| SECONDARY Change in HbA1c (Week 52) |
-1.0; -1.4; -1.5; -1.3; 0.1 | — |
| SECONDARY Change in Body Weight (kg) |
-0.4; -1.2; -2.4; 0.1; -1.1; 0.0 | — |
| SECONDARY Change in Fasting Plasma Glucose |
-1.62; -1.60; -2.37; -2.48; -0.37; -1.13 | — |
| SECONDARY Change in Self-measured Plasma Glucose 7-point Profile (SMPG) - Mean 7-point Profile |
-2.2; -2.6; -3.1; -2.8; -0.8; -1.7 | — |
| SECONDARY Change in Mean Postprandial Increment Over All Meals in SMPG |
-0.7; -1.2; -2.0; -1.1; -0.5; -0.5 | — |
| SECONDARY Change in Body Weight (%) |
-0.64; -1.63; -3.54; 0.08; -1.58; -0.03 | — |
| SECONDARY Change in Body Mass Index |
-0.1; -0.4; -0.9; 0.0; -0.4; 0.0 | — |
| SECONDARY Change in Waist Circumference |
0.5; -0.6; -1.3; 0.0; -0.5; 0.2 | — |
| SECONDARY Change in Total Cholesterol (Ratio to Baseline) |
0.92; 0.93; 0.89; 0.94; 1.00; 0.99 | — |
| SECONDARY Change in HDL Cholesterol (Ratio to Baseline) |
0.97; 0.98; 0.96; 0.99; 1.03; 1.05 | — |
| SECONDARY Change in LDL Cholesterol (Ratio to Baseline) |
0.87; 0.89; 0.85; 0.91; 1.03; 0.99 | — |
| SECONDARY Change in VLDL Cholesterol (Ratio to Baseline) |
1.02; 0.94; 0.93; 0.99; 0.87; 0.86 | — |
| SECONDARY Change in Triglycerides (Ratio to Baseline) |
1.03; 0.94; 0.93; 0.99; 0.87; 0.86 | — |
| SECONDARY Change in Fasting Insulin (Ratio to Baseline) |
1.19; 1.27; 1.10; 1.14; 0.92; 1.07 | — |
| SECONDARY Change in Fasting C-peptide (Ratio to Baseline) |
1.15; 1.24; 1.17; 1.18; 0.98; 1.12 | — |
| SECONDARY Change in Fasting Glucagon (Ratio to Baseline) |
0.95; 0.89; 0.85; 0.91; 0.95; 0.97 | — |
| SECONDARY Change in Fasting Pro-insulin (Ratio to Baseline) |
0.69; 0.68; 0.51; 0.61; 0.85; 0.83 | — |
| SECONDARY Change in Fasting Pro-insulin/Insulin Ratio (Ratio to Baseline) |
0.59; 0.54; 0.49; 0.55; 0.92; 0.78 | — |
| SECONDARY Change in Insulin Resistance (HOMA-IR) (Ratio to Baseline) |
0.98; 1.02; 0.83; 0.86; 0.88; 0.93 | — |
| SECONDARY Change in Beta-cell Function (HOMA-B) (Ratio to Baseline) |
1.71; 1.93; 1.95; 1.89; 1.00; 1.36 | — |
| SECONDARY Participants Who Achieved HbA1c < 7.0% (53 mmol/Mol) ADA Target (Yes/no) |
24; 33; 35; 24; 6; 19 | — |
| SECONDARY Participants Who Achieved HbA1c Below or Equal to 6.5% (48 mmol/Mol), AACE Target (Yes/No) |
13; 24; 28; 16; 2; 30 | — |
| SECONDARY Participants Who Achieved HbA1c Below 7.0% (53 mmol/Mol) Without Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemia Episodes and no Weight Gain (Yes/No) |
15; 26; 30; 15; 4; 28 | — |
| SECONDARY Participants Who Achieved HbA1c Reduction Above or Equal to 1% (10.9 mmol/Mol) and Weight Loss Above or Equal to 3% |
7; 11; 21; 5; 3; 36 | — |
| SECONDARY Participants Who Achieved Weight Loss Above or Equal to 5% (Yes/No) |
1; 5; 16; 0; 3; 42 | — |
| SECONDARY Participants Who Achieved Weight Loss Above or Equal to 10% (Yes/No) |
0; 0; 3; 0; 0; 43 | — |
| SECONDARY Time to Additional Anti-diabetic Medication |
3; 3; 1; 0; 7; 8 | 0.2579 |
| SECONDARY Time to Rescue Medication |
2; 2; 1; 0; 7; 7 | 0.0219 sig |
| SECONDARY Number of Treatment-emergent Adverse Events (TEAEs) |
119; 111; 96; 116; 106 | — |
| SECONDARY Change in Amylase (Ratio to Baseine) |
1.03; 1.10; 1.16; 1.07; 1.02; 1.06 | — |
| SECONDARY Change in Lipase (Ratio to Baseine) |
1.25; 1.35; 1.61; 1.47; 1.04; 1.29 | — |
| SECONDARY Change in Pulse Rate |
1; 2; 2; 2; 0; 1 | — |
| SECONDARY Change in Blood Pressure |
-3; -5; -2; -1; -4; -0 | — |
| SECONDARY Change in ECG Evaluation |
34; 41; 39; 38; 39; 4 | — |
| SECONDARY Change in Physical Examination |
49; 49; 48; 48; 49; 0 | — |
| SECONDARY Change in Eye Examination Category |
39; 45; 37; 37; 39; 4 | — |
| SECONDARY Anti-semaglutide Binding Antibodies (Yes/no) |
0; 1; 1; 49; 48; 47 | — |
| SECONDARY Anti-semaglutide Neutralising Antibodies (Yes/no) |
0; 0; 0; 49; 49; 48 | — |
| SECONDARY Anti-semaglutide Binding Antibodies Cross Reacting With Native GLP-1 (Yes/no) |
0; 0; 1; 49; 49; 47 | — |
| SECONDARY Anti-semaglutide Neutralising Antibodies Cross Reacting With Native GLP-1 (Yes/no) |
0; 0; 0; 49; 49; 48 | — |
| SECONDARY Anti-semaglutide Binding Antibody Levels |
1.58; 2.40 | — |
| SECONDARY Number of Treatment-emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemic Episodes |
0; 0; 0; 2; 0 | — |
| SECONDARY Participants With Treatment-emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemic Episodes |
0; 0; 0; 2; 0 | — |
| SECONDARY Semaglutide Plasma Concentration |
3.7; 9.5; 20.6; 5.3; 13.9; 30.7 | — |
| SECONDARY Change in SF-36: Sub-domains |
-0.22; -0.09; 0.04; 0.09; -0.14; -0.31 | — |
| SECONDARY Change in SF-36: Physical Component Summary (PCS) |
-1.33; -0.38; 0.93; -0.14; 0.20; -1.28 | — |
| SECONDARY Change in SF-36: Mental Component Summary (MCS) |
-1.81; 0.56; -1.61; 0.49; -2.18; -1.56 | — |
| SECONDARY Change From Baseline in DTR-QOL: Total Score |
6.67; 7.98; 11.22; 9.77; 4.18; 6.97 | — |
| SECONDARY Change From Baseline in DTR-QOL: Sub-domains |
5.75; 5.87; 7.90; 10.11; 6.91; 9.31 | — |
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT03018028) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.