Phase 3
Completed N=458
Safety and Efficacy of Oral Semaglutide Versus Dulaglutide Both in Combination With One OAD (Oral Antidiabetic Drug) in Japanese Subjects With Type 2 Diabetes
Source: ClinicalTrials.gov NCT03015220 ↗Enrolled (actual)
458
Serious AEs
4.6%
Results posted
Dec 2019
Primary outcomePrimary: Number of Treatment-emergent Adverse Events (TEAEs) — 330; 350; 324; 178 Events
◆ Published Evidence
Highly cited
207citations · ~35 / year
Safety and efficacy of oral semaglutide versus dulaglutide in Japanese patients with type 2 diabetes (PIONEER 10): an open-label, randomised, active-controlled, phase 3a trial.
Summary
This trial is conducted in Asia. The aim of this trial is to investigate Safety and efficacy of oral semaglutide versus dulaglutide both in combination with one OAD (oral antidiabetic drug) in Japanese subjects with type 2 diabetes.
Linked Publications (5)
-
Safety and efficacy of oral semaglutide versus dulaglutide in Japanese patients with type 2 diabetes (PIONEER 10): an open-label, randomised, active-controlled, phase 3a trial.
-
Effect of Orally Administered Semaglutide Versus Dulaglutide on Diabetes-Related Quality of Life in Japanese Patients with Type 2 Diabetes: The PIONEER 10 Randomized, Active-Controlled Trial.
-
Semaglutide (SUSTAIN and PIONEER) reduces cardiovascular events in type 2 diabetes across varying cardiovascular risk.
-
Efficacy, safety and cardiovascular outcomes of once-daily oral semaglutide in patients with type 2 diabetes: The PIONEER programme.
-
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 Number of Treatment-emergent Adverse Events (TEAEs) |
330; 350; 324; 178 | — |
| SECONDARY Change in HbA1c |
-1.1; -1.7; -2.0; -1.6; -0.8; -1.4 | — |
| SECONDARY Change in Fasting Plasma Glucose |
-1.23; -2.25; -2.72; -2.22; -0.95; -1.96 | — |
| SECONDARY Change in Self-measured Plasma Glucose 7-point Profile (SMPG) - Mean 7-point Profile |
-1.8; -2.7; -3.5; -2.9; -1.7; -2.5 | — |
| SECONDARY Change in Self-measured Plasma Glucose (SMPG) - Mean Postprandial Increment Over All Meals |
-0.9; -1.3; -1.2; -0.7; -0.6; -0.8 | — |
| SECONDARY Change in Body Weight (kg) |
-0.1; -1.0; -2.2; 0.3; 0.0; -0.9 | — |
| SECONDARY Change in Body Weight (%) |
-0.28; -1.49; -3.21; 0.25; -0.02; -1.34 | — |
| SECONDARY Change in Body Mass Index (BMI) |
-0.1; -0.4; -0.8; 0.1; -0.0; -0.3 | — |
| SECONDARY Change in Waist Circumference |
0.0; -0.6; -1.2; 0.3; -0.1; -0.8 | — |
| SECONDARY Change in Fasting Total Cholesterol (Ratio to Baseline) |
0.96; 0.91; 0.91; 0.92; 0.98; 0.95 | — |
| SECONDARY Change in Fasting Low-density Lipoprotein (LDL) - Cholesterol (Ratio to Baseline) |
0.92; 0.88; 0.87; 0.88; 0.98; 0.94 | — |
| SECONDARY Change in Fasting High-density Lipoprotein (HDL) - Cholesterol (Ratio to Baseline) |
1.02; 0.99; 1.00; 0.99; 1.03; 0.99 | — |
| SECONDARY Change in Fasting Very-low Density Lipoprotein (VLDL) - Cholesterol (Ratio to Baseline) |
1.03; 0.92; 0.96; 0.93; 0.90; 0.87 | — |
| SECONDARY Change in Fasting Triglyceride (Ratio to Baseline) |
1.03; 0.91; 0.96; 0.93; 0.89; 0.87 | — |
| SECONDARY Participants Who Achieve HbA1c Below 7% (53 mmol/Mol), American Diabetes Association Target (Yes/No) |
59; 96; 105; 45; 69; 32 | — |
| SECONDARY Participants Who Achieve HbA1c Below or Equal to 6.5% (48 mmol/Mol), American Association of Clinical Endocrinologists Target (Yes/No) |
40; 67; 88; 31; 88; 61 | — |
| SECONDARY Participants Who Achieve HbA1c Below 7.0% (53 mmol/Mol) Without Severe or Blood Glucose Confirmed Symptomatic Hypoglycaemia Episodes and no Weight Gain (Yes/No) |
39; 63; 84; 25; 89; 65 | — |
| SECONDARY Participants Who Achieve HbA1c Reduction More Than or Equal to 1% (10.9 mmol/Mol) and Weight Loss More Than or Equal to 3% (Yes/No) |
15; 34; 62; 8; 113; 94 | — |
| SECONDARY Participants Who Achieve Weight Loss More Than or Equal to 5% (Yes/No). |
6; 23; 39; 4; 122; 105 | — |
| SECONDARY Participants Who Achieve Weight Loss More Than or Equal to 10% (Yes/No) |
0; 6; 8; 1; 128; 122 | — |
| SECONDARY Time to Additional Anti-diabetic Medication |
1; 3; 6; 1; 24; 13 | 0.2963 |
| SECONDARY Time to Rescue Medication |
0; 0; 1; 1; 22; 8 | 0.1672 |
| SECONDARY Change in Amylase (Ratio to Baseline) |
1.01; 1.07; 1.10; 1.05; 1.03; 1.10 | — |
| SECONDARY Change in Lipase (Ratio to Baseline) |
1.15; 1.27; 1.40; 1.14; 1.11; 1.36 | — |
| SECONDARY Change in Pulse Rate |
3; 4; 4; 4; 3; 3 | — |
| SECONDARY Change in Blood Pressure |
-3.0; -5.0; -6.0; -4.0; -2.0; -2.0 | — |
| SECONDARY Change in ECG Evaluation |
103; 110; 99; 54; 4; 3 | — |
| SECONDARY Change in Physical Examination |
128; 132; 128; 60; 1; 0 | — |
| SECONDARY Change in Eye Examination Category |
96; 97; 90; 48; 7; 2 | — |
| SECONDARY Number of Treatment-emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemic Episodes |
4; 4; 4; 0 | — |
| SECONDARY Participants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes |
3; 3; 4; 0 | — |
| SECONDARY Change in SF-36v2 (Acute Version) Health Survey Scores: Scores From the 8 Domains, the Physical Component Summary (PCS) and the Mental Component Summary (MCS) |
-0.18; 0.08; -0.06; -0.24; -0.37; 0.70 | — |
| SECONDARY Diabetes Therapy-Related Quality of Life (DTR-QoL): Total Score and Scores for the 4 Domains |
6.44; 6.93; 4.88; 5.29; 4.73; 6.81 | — |
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 60 days prior to day of screening
- HbA1c (glycosylated haemoglobin) between 7.0%-10.5% (53-91 mmol/mol) (both inclusive)
- OAD (oral antidiabetic drug) monotherapy with stable daily dose for at least 60 days prior to the day of screening of one of SU (sulphonylurea) glinide , TZD (thiazolidinedione), α-GI (alpha-glucosidase inhibitor) or SGLT-2 (sodium-glucose cotransporter-2) inhibitor according to Japanese labelling
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 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 (TIA) within the past 180 days prior to the day of screening and randomisation
- 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
- 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 agonists (GLP-1 RA) or once weekly dipeptidyl peptidase-4 (DPP-4) inhibitor in a period of 90 days before the day of screening
- For subjects treated with an OAD other than TZD at screening: Treatment with TZD in a period of 90 days before the day of screening
- Treatment with any medication for the indication of diabetes or obesity in addition to background OAD medication (SU, glinide, TZD, α-GI or SGLT-2 inhibitor) in a period of 60 days before the day of screening with the exception of short-term insulin treatment for acute illness for a total of at least 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)
- History of diabetic ketoacidosis
Data sourced from ClinicalTrials.gov (NCT03015220) 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.