Phase 3
Completed N=1,864
Efficacy and Long-term Safety of Oral Semaglutide Versus Sitagliptin in Subjects With Type 2 Diabetes
Source: ClinicalTrials.gov NCT02607865 ↗Enrolled (actual)
1,864
Serious AEs
11.5%
Results posted
Feb 2020
Primary outcomePrimary: Change in HbA1c: Week 26 — -0.6; -1.1; -1.3; -0.8 Percentage of HbA1c — p=< 0.0001
◆ Published Evidence
Highly cited
393citations · ~56 / year
Effect of Additional Oral Semaglutide vs Sitagliptin on Glycated Hemoglobin in Adults With Type 2 Diabetes Uncontrolled With Metformin Alone or With Sulfonylurea: The PIONEER 3 Randomized Clinical Trial.
Summary
This trial is conducted globally. The aim of the trial is to investigate efficacy and long-term safety of oral semaglutide versus sitagliptin in subjects with type 2 diabetes.
Linked Publications (5)
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Effect of Additional Oral Semaglutide vs Sitagliptin on Glycated Hemoglobin in Adults With Type 2 Diabetes Uncontrolled With Metformin Alone or With Sulfonylurea: The PIONEER 3 Randomized Clinical 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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Long-Term Cost Effectiveness of Oral Semaglutide Versus Empagliflozin and Sitagliptin for the Treatment of Type 2 Diabetes in the Swedish Setting.
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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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Cost-Effectiveness of Semaglutide vs. Empagliflozin, Canagliflozin, and Sitagliptin for Treatment of Patients with Type 2 Diabetes in Denmark: A Decision-Analytic Modelling Study.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in HbA1c: Week 26 |
-0.6; -1.1; -1.3; -0.8; -0.6; -1.2 | < 0.0001 sig |
| SECONDARY Change in Body Weight: Week 26 |
-1.2; -2.2; -3.1; -0.6; -1.2; -2.2 | < 0.0001 sig |
| SECONDARY Change in HbA1c: Weeks 52 and 78 |
-0.6; -1.0; -1.2; -0.7; -0.6; -0.9 | — |
| SECONDARY Change in Body Weight (kg): Weeks 52 and 78 |
-1.6; -2.5; -3.5; -0.7; -1.8; -2.8 | — |
| SECONDARY Change in Body Weight (%) |
-1.23; -2.36; -3.44; -0.64; -1.65; -2.63 | — |
| SECONDARY Change in FPG |
-0.83; -1.17; -1.67; -0.90; -0.98; -1.28 | — |
| SECONDARY Change in BMI |
-0.4; -0.8; -1.1; -0.2; -0.6; -0.9 | — |
| SECONDARY Change in Waist Circumference |
-0.7; -1.8; -2.3; -0.6; -1.3; -2.3 | — |
| SECONDARY Change in Total Cholesterol (Ratio to Baseline) |
1.00; 0.98; 0.97; 1.00; 1.00; 0.99 | — |
| SECONDARY Change in LDL Cholesterol (Ratio to Baseline) |
1.02; 0.98; 0.98; 1.02; 1.02; 0.99 | — |
| SECONDARY Change in VLDL Cholesterol (Ratio to Baseline) |
0.99; 0.96; 0.91; 0.97; 1.00; 0.98 | — |
| SECONDARY Change in HDL Cholesterol (Ratio to Baseline) |
0.97; 0.99; 0.98; 0.99; 0.99; 1.01 | — |
| SECONDARY Change in Triglycerides (Ratio to Baseline) |
0.99; 0.96; 0.92; 0.97; 1.00; 0.97 | — |
| SECONDARY Change in Free Fatty Acids (Ratio to Baseline) |
0.96; 0.91; 0.88; 0.90; 1.03; 1.00 | — |
| SECONDARY Change in SMPG - Mean 7-point Profile |
-1.1; -1.5; -1.7; -1.2; -1.3; -1.5 | — |
| SECONDARY Change in SMPG - Mean Postprandial Increment Over All Meals |
-0.4; -0.4; -0.6; -0.6; -0.4; -0.4 | — |
| SECONDARY Participants Who Achieve HbA1c <7.0% (53 mmol/Mol) ADA Target (Yes/no) |
116; 192; 246; 144; 319; 246 | — |
| SECONDARY Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol) AACE Target (Yes/no) |
55; 116; 161; 61; 380; 322 | — |
| SECONDARY Participants Who Achieve Weight Loss ≥5% (Yes/no) |
53; 81; 131; 45; 385; 359 | — |
| SECONDARY Participants Who Achieve Weight Loss ≥10% (Yes/no) |
5; 23; 29; 8; 433; 417 | — |
| SECONDARY Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no) |
87; 155; 208; 90; 348; 283 | — |
| SECONDARY Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no) |
55; 117; 166; 43; 380; 321 | — |
| SECONDARY Time to Additional Anti-diabetic Medication |
33; 20; 15; 20; 137; 86 | =0.0063 sig |
| SECONDARY Time to Rescue Medication |
25; 11; 5; 13; 121; 73 | =0.0160 sig |
| SECONDARY Number of TEAEs During Exposure to Trial Product |
1774; 1686; 1824; 1852 | — |
| SECONDARY Change in Amylase (Ratio to Baseline) |
1.03; 1.07; 1.14; 1.08; 1.03; 1.09 | — |
| SECONDARY Change in Lipase (Ratio to Baseline) |
1.07; 1.13; 1.26; 1.14; 1.06; 1.15 | — |
| SECONDARY Change in Pulse Rate |
1; 2; 3; 0; 0; 2 | — |
| SECONDARY Change in SBP and DBP |
-2; -2; -3; -2; -2; -4 | — |
| SECONDARY Change in ECG Evaluation |
211; 214; 230; 204; 38; 42 | — |
| SECONDARY Change in Physical Examination |
431; 425; 432; 424; 30; 38 | — |
| SECONDARY Change in Eye Examination Category |
302; 299; 305; 297; 130; 138 | — |
| SECONDARY Occurrence of Anti-semaglutide Binding Antibodies (Yes/no) |
1; 2; 3 | — |
| SECONDARY Occurrence of Anti-semaglutide Neutralising Antibodies (Yes/no) |
0; 0; 0 | — |
| SECONDARY Occurrence of Anti-semaglutide Binding Antibodies Cross Reacting With Native GLP-1 (Yes/no) |
0; 1; 1 | — |
| SECONDARY Occurrence of Anti-semaglutide Neutralising Antibodies Cross Reacting With Native GLP-1 (Yes/no) |
0; 0; 0 | — |
| SECONDARY Anti-semaglutide Binding Antibody Levels |
9.82; 1.93; 3.28; 2.39; 2.05; 2.24 | — |
| SECONDARY Number of Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes |
56; 42; 60; 76 | — |
| SECONDARY Participants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes |
23; 24; 36; 39 | — |
| SECONDARY Semaglutide Plasma Concentration in a Subset of the Participants for Population PK Analyses |
0.4; 0.4; 0.4; 1.5; 1.5; 1.6 | — |
| SECONDARY Change in SF-36v2 (Acute Version) Health Survey: Scores From the 8 Domains, the Physical Component Summary (PCS) and the Mental Component Summary (MCS) |
0.37; 1.12; 0.63; 0.46; 0.29; 0.64 | — |
| SECONDARY Change in IWQoL-Lite-CT: Total Score and Scores From the 4 Domains |
3.25; 2.38; 2.87; 1.97; 1.84; 3.03 | — |
| SECONDARY Change in CoEQ: Scores From the 4 Domains and the 19 Items |
-0.41; -0.37; -0.54; -0.18; -0.28; -0.23 | — |
Eligibility Criteria
Inclusion Criteria
- Male or female, age at least 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 T2DM (type 2 diabetes mellitus) for at least 90 days prior to day of screening
- HbA1c (glycosylated haemoglobin) 7.0-10.5 % (53-91 mmol/mol) (both inclusive).
- Stable daily dose of metformin (equal or above 1500 mg or maximum tolerated dose as documented in subject medical record) alone or in combination with SU (= half of the maximum approved dose according to local label or maximum tolerated dose as documented in subject medical record) within 90 days prior to the day of screening
Exclusion Criteria
- Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using adequate contraceptive methods (adequate contraceptive measures as required by local regulation or practice). For certain specific countries: Additional specific requirements apply
- 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 hospitalization for unstable angina and/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.
- Renal impairment defined as estimated Glomerular Filtration Rate (eGFR) below 60 mL/min/1.73 m^2 as per Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
- History or presence of malignant neoplasms within the last 5 years (except basal and squamous cell skin cancer and in-situ carcinomas)
Data sourced from ClinicalTrials.gov (NCT02607865) 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.