Phase 3 · Semaglutide

PIONEER 2 trial results

Efficacy and Safety of Oral Semaglutide Versus Empagliflozin in Subjects With Type 2 Diabetes Mellitus

Participants
822
Status
completed
Completed
2018-03-08
Sponsor
Novo Nordisk A/S

As posted on ClinicalTrials.gov (NCT02863328), updated at source Jul 20, 2022. Read again whenever the registry updates it. Registry figures can differ from a published paper, which may use another analysis.

Primary outcome

What PIONEER 2 measured first

Change in HbA1cPercentage-point of HbA1c · Week 0, week 26 · mean
MeasureOral Semaglutide 14 mgn=411Empagliflozin 25 mgn=410
In-trial-1.3(1.1)-0.9(0.9)
On-treatment without rescue medication-1.5(1.1)-0.9(0.9)
Side effects by arm

Side effects in PIONEER 2

Percent of participants affected, Week 0 to week 57 (52 weeks treatment period + 5 weeks follow-up period). Results are based on the safety analysis set (SAS), which comprised all randomised participants who received at least one.... The most common events the registry lists.

EventOral Semaglutide 14 mgEmpagliflozin 25 mg
Any serious event6.6%9%
Nausea19.8%2.4%
Diarrhoea9.3%3.2%
Vomiting7.3%1.7%
Decreased appetite5.1%0.5%
Influenza2%5.1%
Secondary outcomes

What else it measured

Change in Body Weight (Kg)Kilogram (Kg) · Week 0, week 26 · mean
MeasureOral Semaglutide 14 mgn=411Empagliflozin 25 mgn=410
In-trial-3.9(4.4)-3.8(3.8)
On-treatment without rescue medication-4.3(4.4)-3.9(3.8)
Change in HbA1c (%)Percentage of HbA1c · Week 0, week 52 · mean
Oral Semaglutide 14 mgn=384Empagliflozin 25 mgn=382
-1.3(1.2)-0.9(1.0)
Change in Body Weight (kg)Kg · Week 0, week 52 · mean
Oral Semaglutide 14 mgn=386Empagliflozin 25 mgn=383
-4.0(5.5)-3.7(4.3)
Change in Fasting Plasma GlucoseMillimoles per liter (mmol/L) · Week 0, week 26, week 52 · mean
MeasureOral Semaglutide 14 mgn=411Empagliflozin 25 mgn=410
Week 26-2.01(2.56)-2.08(2.17)
Week 52-2.04(2.50)-2.14(2.36)
Change in SMPG : Mean of the 7-point Profilemmol/L · Week 0, week 26 and week 52 · mean
MeasureOral Semaglutide 14 mgn=411Empagliflozin 25 mgn=410
Week 26-2.3(2.1)-1.9(2.1)
Week 52-2.3(2.3)-2.1(2.3)
Change in SMPG : Mean Postprandial Increment Over All Mealsmmol/L · Week 0, week 26 and week 52 · mean
MeasureOral Semaglutide 14 mgn=411Empagliflozin 25 mgn=410
Week 26-0.5(1.8)-0.4(2.0)
Week 52-0.6(1.8)-0.4(1.9)
Change in Fasting C-peptide (Ratio to Baseline)Ratio of C-peptide · Week 0, week 26 and week 52 · geometric mean
MeasureOral Semaglutide 14 mgn=411Empagliflozin 25 mgn=410
week 261.10(35.7)0.89(29.4)
week 521.09(37.2)0.92(31.6)
Change in Fasting Insulin (Ratio to Baseline)Ratio of insulin · Week 0, week 26 and week 52 · geometric mean
MeasureOral Semaglutide 14 mgn=411Empagliflozin 25 mgn=410
Week 261.06(50.5)0.77(54.1)
Week 521.03(52.8)0.77(53.7)
Change in Fasting Pro-insulin (Ratio to Baseline)Ratio of pro-insulin · Week 0, week 26 and week 52 · geometric mean
MeasureOral Semaglutide 14 mgn=411Empagliflozin 25 mgn=410
Week 260.72(74.6)0.66(61.9)
Week 520.74(80.5)0.69(57.8)
Change in Fasting Glucagon (Ratio to Baseline)Ratio of glucagon · Week 0, week 26 and week 52 · geometric mean
MeasureOral Semaglutide 14 mgn=411Empagliflozin 25 mgn=410
Week 260.91(28.0)1.01(27.5)
Week 520.89(27.8)0.95(27.6)
Change in HOMA-IR (Ratio to Baseline)Ratio of HOMA-IR · Week 0, week 26 and week 52 · geometric mean
MeasureOral Semaglutide 14 mgn=411Empagliflozin 25 mgn=410
Week 260.83(63.8)0.61(58.7)
Week 520.81(64.9)0.60(60.4)
Change in HOMA-B (Ratio to Baseline)Ratio of HOMA-B · Week 0, week 26 and week 52 · geometric mean
MeasureOral Semaglutide 14 mgn=411Empagliflozin 25 mgn=410
Week 261.67(69.5)1.16(65.0)
Week 521.66(72.9)1.17(69.9)
The trial

How PIONEER 2 was run

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.

  • 14 mg oral semaglutide
  • 25 mg empagliflozin
Who could join the trial

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

Published papers

Papers from PIONEER 2

Trial averages do not predict what one person will experience. Results are shown as the registry posts them, without interpretation.

GLPcompare is an informational data platform, not a medical provider or pharmacy. Nothing here is medical advice, a diagnosis, or a recommendation to start, stop, or change any treatment. Data is aggregated from public sources and can be incomplete or out of date. Always confirm with a licensed clinician and the current FDA label.