Phase 3
Completed N=711
Efficacy and Safety of Oral Semaglutide Versus Liraglutide and Versus Placebo in Subjects With Type 2 Diabetes Mellitus
Source: ClinicalTrials.gov NCT02863419 ↗Enrolled (actual)
711
Serious AEs
9.6%
Results posted
Nov 2019
Primary outcomePrimary: Change in HbA1c (Week 26) — -1.2; -1.1; -0.1; -1.4 Percentage of HbA1c — p=<0.0001
◆ Published Evidence
Highly cited
582citations · ~83 / year
Oral semaglutide versus subcutaneous liraglutide and placebo in type 2 diabetes (PIONEER 4): a randomised, double-blind, phase 3a trial.
Summary
This trial is conducted globally. The aim of this trial is to investigate efficacy and safety of oral Semaglutide versus Liraglutide and versus Placebo in Subjects with Type 2 Diabetes Mellitus.
Linked Publications (5)
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Oral semaglutide versus subcutaneous liraglutide and placebo in type 2 diabetes (PIONEER 4): a randomised, double-blind, phase 3a trial.
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Efficacy and safety of oral semaglutide by subgroups of patient characteristics in the PIONEER phase 3 programme.
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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.
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Oral Semaglutide Reduces HbA<sub>1c</sub> and Body Weight in Patients with Type 2 Diabetes Regardless of Background Glucose-Lowering Medication: PIONEER Subgroup Analyses.
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Early use of oral semaglutide in the UK: A cost-effectiveness analysis versus continuing metformin and SGLT-2 inhibitor therapy.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in HbA1c (Week 26) |
-1.2; -1.1; -0.1; -1.4; -1.2; -0.1 | <0.0001 sig |
| SECONDARY Change in Body Weight (Week 26) |
-4.4; -3.2; -0.6; -4.7; -3.3; -0.7 | 0.0003 sig |
| SECONDARY Change in HbA1c (Week 52) |
-1.2; -0.9; -0.1 | — |
| SECONDARY Change in Body Weight (Week 52) |
-4.4; -3.1; -1.0 | — |
| SECONDARY Change in Body Weight (%) |
-4.89; -3.33; -0.60; -4.94; -3.25; -0.99 | — |
| SECONDARY Change in Fasting Plasma Glucose |
-2.04; -1.91; -0.33; -1.91; -1.54; -0.66 | — |
| SECONDARY Change in Body Mass Index |
-1.6; -1.1; -0.2; -1.6; -1.1; -0.4 | — |
| SECONDARY Change in Waist Circumference |
-4.2; -3.0; -1.2; -4.4; -2.7; -1.7 | — |
| SECONDARY Change in Total Cholesterol - Ratio to Baseline |
0.96; 0.97; 0.99; 0.98; 0.98; 1.02 | — |
| SECONDARY Change in Low-density Lipoprotein (LDL) Cholesterol - Ratio to Baseline |
0.95; 0.97; 0.99; 0.99; 1.00; 1.06 | — |
| SECONDARY Change in Very Low Density Lipoprotein (VLDL) Cholesterol - Ratio to Baseline |
0.90; 0.91; 1.02; 0.87; 0.90; 0.98 | — |
| SECONDARY Change in High-density Lipoprotein (HDL) Cholesterol - Ratio to Baseline |
1.02; 1.02; 1.02; 1.03; 1.01; 1.00 | — |
| SECONDARY Change in Triglycerides - Ratio to Baseline |
0.89; 0.91; 1.01; 0.87; 0.89; 0.97 | — |
| SECONDARY Change in Free Fatty Acids - Ratio to Baseline |
0.94; 0.95; 1.06; 0.83; 0.87; 0.89 | — |
| SECONDARY Change in SMPG - Mean 7-point Profile |
-2.2; -2.0; -0.7; -2.2; -1.8; -0.9 | — |
| SECONDARY Change in SMPG - Mean Postprandial Increment Over All Meals |
-0.7; -0.4; -0.2; -0.5; -0.5; -0.4 | — |
| SECONDARY Participants Who Achieve HbA1c <7.0% (53 mmol/Mol) ADA Target (Yes/no) |
188; 168; 19; 90; 104; 115 | — |
| SECONDARY Participants Who Achieve HbA1c <6.5% (48 mmol/Mol) AACE Target (Yes/no) |
133; 116; 7; 145; 156; 127 | — |
| SECONDARY Participants Who Achieve Weight Loss ≥5% (Yes/no) |
121; 75; 10; 157; 196; 124 | — |
| SECONDARY Participants Who Achieve Weight Loss ≥ 10% (Yes/no) |
39; 16; 0; 239; 255; 134 | — |
| SECONDARY Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no) |
169; 145; 15; 109; 126; 119 | — |
| SECONDARY Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no) |
130; 93; 5; 148; 178; 129 | — |
| SECONDARY Time to Additional Anti-diabetic Medication |
20; 16; 12; 39; 29; 46 | 0.4915 |
| SECONDARY Time to Rescue Medication |
10; 9; 11; 20; 18; 43 | 0.6252 |
| SECONDARY Number of Treatment-emergent Adverse Events (TEAEs) During Exposure to Trial Product |
973; 927; 300 | — |
| SECONDARY Change in Amylase - Ratio to Baseline |
1.13; 1.11; 0.99; 1.14; 1.10; 0.98 | — |
| SECONDARY Change in Lipase - Ratio to Baseline |
1.33; 1.40; 0.99; 1.28; 1.32; 0.96 | — |
| SECONDARY Change in Pulse Rate |
2; 3; 0; 2; 3; 0 | — |
| SECONDARY Change in SBP and DBP |
-4; -4; -2; -3; -3; -0 | — |
| SECONDARY Change in ECG Evaluation |
130; 123; 67; 19; 20; 6 | — |
| SECONDARY Change in Physical Examination |
260; 249; 128; 23; 26; 12 | — |
| SECONDARY Change in Eye Examination Category |
130; 144; 57; 10; 15; 5 | — |
| SECONDARY Occurrence of Anti-semaglutide Binding Antibodies (Yes/no) |
— | — |
| SECONDARY Occurrence of Anti-semaglutide Neutralising Antibodies (Yes/no) |
— | — |
| SECONDARY Occurrence of Anti-semaglutide Binding Antibodies Cross Reacting With Native GLP-1 (Yes/no) |
— | — |
| SECONDARY Occurrence of Anti-semaglutide Neutralising Antibodies Cross Reacting With Native GLP-1 (Yes/no) |
— | — |
| SECONDARY Anti-semaglutide Binding Antibody Levels |
— | — |
| SECONDARY Number of Treatment-emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemic Episodes |
2; 9; 3 | — |
| SECONDARY Participants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes |
2; 7; 3 | — |
| SECONDARY Change in DTSQs: Individual Items and Total Treatment Satisfaction Score (6 of the 8 Items Summed) |
0.72; 0.73; 0.28; 0.67; 0.70; 0.48 | — |
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
- Male or female, age above or equal to 18 years at the time of signing informed consent. For Japan only: Male or female, age at least 20 years at the time of signing informed consent
- Diagnosed with type 2 diabetes mellitus for at least 90 days prior to day of screening.
- HbA1c (glycosylated haemoglobin) of 7.0-9.5 % (53-80.3 mmol/mol) (both inclusive)
- Stable daily dose of metformin (above or equal to 1500 mg or maximum tolerated dose as documented in the subject medical record) alone or in combination with a stable daily dose of a SGLT-2 (sodium-glucose co-transporter-2) inhibitor for at least 90 days prior to day of screening (fixed-dose combinations are allowed)
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 certain specific countries: Additional specific requirements apply
- 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
- 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 ALT (alanine aminotransferase) above 2.5 × upper normal limit (UNL)
- Renal impairment defined as estimated Glomerular Filtration Rate (eGFR) below 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 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 carcinoma in situ)
- History of diabetic ketoacidosis
Data sourced from ClinicalTrials.gov (NCT02863419) 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.