Phase 3
Completed N=821
Efficacy and Safety of Oral Semaglutide Versus Empagliflozin in Subjects With Type 2 Diabetes Mellitus
Source: ClinicalTrials.gov NCT02863328 ↗Enrolled (actual)
821
Serious AEs
7.8%
Results posted
Dec 2019
Primary outcomePrimary: Change in HbA1c — -1.3; -0.9; -1.5; -0.9 Percentage-point of HbA1c — p=< 0.0001
◆ Published Evidence
Highly cited
438citations · ~63 / year
Oral Semaglutide Versus Empagliflozin in Patients With Type 2 Diabetes Uncontrolled on Metformin: The PIONEER 2 Trial.
Summary
This trial is conducted globally. The aim of this trial is to investigate Efficacy and Safety of Oral Semaglutide versus Empagliflozin in Subjects with Type 2 Diabetes Mellitus.
Linked Publications (5)
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Oral Semaglutide Versus Empagliflozin in Patients With Type 2 Diabetes Uncontrolled on Metformin: The PIONEER 2 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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Impact of semaglutide on high-sensitivity C-reactive protein: exploratory patient-level analyses of SUSTAIN and PIONEER randomized clinical 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 |
-1.3; -0.9; -1.5; -0.9 | < 0.0001 sig |
| SECONDARY Change in Body Weight (Kg) |
-4.0; -3.7 | — |
| SECONDARY Change in HbA1c (%) |
-1.3; -0.9 | — |
| SECONDARY Change in Body Weight (kg) |
-4.0; -3.7 | — |
| SECONDARY Change in Fasting Plasma Glucose |
-2.01; -2.08; -2.04; -2.14 | — |
| SECONDARY Change in SMPG : Mean of the 7-point Profile |
-2.3; -1.9; -2.3; -2.1 | — |
| SECONDARY Change in SMPG : Mean Postprandial Increment Over All Meals |
-0.5; -0.4; -0.6; -0.4 | — |
| SECONDARY Change in Fasting C-peptide (Ratio to Baseline) |
1.10; 0.89; 1.09; 0.92 | — |
| SECONDARY Change in Fasting Insulin (Ratio to Baseline) |
1.06; 0.77; 1.03; 0.77 | — |
| SECONDARY Change in Fasting Pro-insulin (Ratio to Baseline) |
0.72; 0.66; 0.74; 0.69 | — |
| SECONDARY Change in Fasting Glucagon (Ratio to Baseline) |
0.91; 1.01; 0.89; 0.95 | — |
| SECONDARY Change in HOMA-IR (Ratio to Baseline) |
0.83; 0.61; 0.81; 0.60 | — |
| SECONDARY Change in HOMA-B (Ratio to Baseline) |
1.67; 1.16; 1.66; 1.17 | — |
| SECONDARY Change in C-reactive Protein (Ratio to Baseline) |
0.69; 0.98; 0.68; 0.90 | — |
| SECONDARY Change in Body Weight (%) |
-4.34; -4.14; -4.38; -4.09 | — |
| SECONDARY Change in Body Mass Index |
-1.4; -1.4; -1.5; -1.4 | — |
| SECONDARY Change in Waist Circumference |
-3.9; -2.9; -3.7; -2.9 | — |
| SECONDARY Change in Fasting Total Cholesterol (Ratio to Baseline) |
0.96; 1.02; 0.97; 1.01 | — |
| SECONDARY Change in Fasting LDL Cholesterol (Ratio to Baseline) |
0.96; 1.03; 0.97; 1.03 | — |
| SECONDARY Change in Fasting HDL Cholesterol (Ratio to Baseline) |
1.01; 1.07; 1.01; 1.06 | — |
| SECONDARY Change in Fasting VLDL Cholesterol (Ratio to Baseline) |
0.89; 0.91; 0.89; 0.90 | — |
| SECONDARY Change in Fasting Free Fatty Acids (Ratio to Baseline) |
0.95; 1.05; 0.88; 0.97 | — |
| SECONDARY Change in Fasting Triglycerides (Ratio to Baseline) |
0.88; 0.90; 0.89; 0.90 | — |
| SECONDARY Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) ADA Target (Yes/no) |
262; 158; 130; 237; 254; 165 | — |
| SECONDARY Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol), AACE Target (Yes/no) |
186; 68; 206; 327; 182; 83 | — |
| SECONDARY Participants Who Achieve Weight Loss ≥5% (Yes/no) |
162; 143; 231; 253; 156; 150 | — |
| SECONDARY Participants Who Achieve Weight Loss ≥10% (Yes/no) |
49; 27; 344; 369; 58; 30 | — |
| SECONDARY Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no) |
237; 141; 155; 254; 214; 149 | — |
| SECONDARY Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no) |
177; 111; 215; 284; 164; 101 | — |
| SECONDARY Time to Additional Anti-diabetic Medication |
17; 13; 52; 56 | 0.3552 |
| SECONDARY Time to Rescue Medication |
8; 5; 31; 44 | 0.2250 |
| SECONDARY Number of Treatment-emergent Adverse Events (TEAE) |
1022; 948 | — |
| SECONDARY Change in Amylase (Ratio to Baseline) |
1.15; 1.10; 1.13; 1.11 | — |
| SECONDARY Change in Lipase (Ratio to Baseline) |
1.37; 1.10; 1.27; 1.07 | — |
| SECONDARY Change in Pulse Rate |
1; -2; 1; -2 | — |
| SECONDARY Change in Blood Pressure (Systolic and Diastolic Blood Pressure) |
-5; -5; -5; -4; -2; -3 | — |
| SECONDARY Change in ECG |
207; 203; 30; 37; 1; 2 | — |
| SECONDARY Change in Physical Examination |
381; 372; 24; 34; 5; 3 | — |
| SECONDARY Change in Eye Examination |
295; 295; 107; 102; 7; 10 | — |
| SECONDARY Occurrence of Anti-semaglutide Binding Antibodies (Yes/no) |
2 | — |
| 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 |
2.75; 2.17 | — |
| SECONDARY Number of Treatment-emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemic Episodes |
10; 9 | — |
| SECONDARY Participants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes (Yes/no) |
7; 8 | — |
| SECONDARY Semaglutide Plasma Concentrations for Population PK Analyses |
3.5; 15.6; 14.4 | — |
| SECONDARY SNAC Plasma Concentrations |
559; 375; 474; 373; 448; 301 | — |
| SECONDARY Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) |
0.87; 0.99; 0.57; 0.84; 0.07; 0.56 | — |
| SECONDARY Change in CoEQ: Scores From the 4 Domains and the 19 Items |
0.46; 0.21; 0.44; 0.18; 0.08; 0.19 | — |
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
- Diagnosed with type 2 diabetes mellitus at least 90 days prior to day of screening
- HbA1c (glycosylated haemoglobin) of 7.0-10.5 % (53-91 mmol/mol) (both inclusive)
- Stable daily dose of metformin (at least 1500 mg or maximum tolerated dose as documented in the subject medical record) at least 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 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 or Medullary Thyroid Carcinoma
- 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 within the past 180 days prior to the day of screening
- Subjects presently classified as being in New York Heart Association Class IV
- Planned coronary, carotid or peripheral artery revascularisation known on the day of screening
- Subjects with ALT (alanine aminotransferase) above 2.5 x upper normal limit
- Renal impairment defined as Estimated Glomerular Filtration Rate 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 (NCT02863328) 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.