Phase 3 · Semaglutide

PIONEER 3 trial results

Efficacy and Long-term Safety of Oral Semaglutide Versus Sitagliptin in Subjects With Type 2 Diabetes

Participants
1,864
Status
completed
Completed
2018-03-28
Sponsor
Novo Nordisk A/S

As posted on ClinicalTrials.gov (NCT02607865), 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 3 measured first

Change in HbA1c: Week 26Percentage of HbA1c · Week 0, week 26 · mean
MeasureOral Semaglutide 3 mgn=466Oral Semaglutide 7 mgn=465Oral Semaglutide 14 mgn=465Sitagliptin 100 mgn=467
In-trial-0.6(1.0)-1.1(1.1)-1.3(1.0)-0.8(0.9)
On-treatment without rescue medication-0.6(1.0)-1.2(1.1)-1.4(1.0)-0.8(0.9)
Side effects by arm

Side effects in PIONEER 3

Percent of participants affected, Week 0 to week 83 (78 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 3 mgOral Semaglutide 7 mgOral Semaglutide 14 mgSitagliptin 100 mg
Any serious event13.7%10.1%9.5%12.4%
Nausea7.3%13.4%15.1%6.7%
Diarrhoea9.4%11.4%12%7.9%
Nasopharyngitis11.4%10.6%10.1%10.1%
Vomiting2.8%5.8%9%4.1%
Headache6.2%6.5%7.7%7.7%
Upper respiratory tract infection7.7%7.5%5.6%6.9%
Decreased appetite1.7%3%6.9%3%
Influenza6.2%5.2%3.9%6.4%
Arthralgia4.5%2.8%4.3%6.2%
Back pain5.2%5.4%5.2%6.2%
Hypertension6.2%5.2%5.6%6.2%
Urinary tract infection6.2%4.5%4.9%5.6%
Diabetic retinopathy5.8%5.2%3.4%5.6%
Secondary outcomes

What else it measured

Change in Body Weight: Week 26Kg · Week 0, week 26 · mean
MeasureOral Semaglutide 3 mgn=466Oral Semaglutide 7 mgn=465Oral Semaglutide 14 mgn=465Sitagliptin 100 mgn=467
In-trial-1.2(3.2)-2.2(3.9)-3.1(3.8)-0.6(3.2)
on-treatment without rescue medication-1.2(3.3)-2.2(4.0)-3.2(3.8)-0.6(3.2)
Change in HbA1c: Weeks 52 and 78Percentage of HbA1c · Week 0, week 52, week 78 · mean
MeasureOral Semaglutide 3 mgn=466Oral Semaglutide 7 mgn=465Oral Semaglutide 14 mgn=465Sitagliptin 100 mgn=467
Week 52-0.6(1.1)-1.0(1.2)-1.2(1.1)-0.7(1.1)
Week 78-0.6(1.1)-0.9(1.3)-1.1(1.1)-0.7(1.1)
Change in Body Weight (kg): Weeks 52 and 78Kg · Week 0, week 52, week 78 · mean
MeasureOral Semaglutide 3 mgn=466Oral Semaglutide 7 mgn=465Oral Semaglutide 14 mgn=465Sitagliptin 100 mgn=467
Week 52-1.6(4.1)-2.5(4.9)-3.5(4.7)-0.7(3.7)
Week 78-1.8(4.9)-2.8(5.4)-3.2(4.9)-1.0(4.1)
Change in Body Weight (%)Percentage change · Week 0, week 26, week 52, week 78 · mean
MeasureOral Semaglutide 3 mgn=466Oral Semaglutide 7 mgn=465Oral Semaglutide 14 mgn=465Sitagliptin 100 mgn=467
Week 26-1.23(3.57)-2.36(4.09)-3.44(4.21)-0.64(3.38)
Week 52-1.65(4.28)-2.63(5.09)-3.83(5.14)-0.76(3.91)
Week 78-1.87(4.87)-2.92(5.67)-3.47(5.34)-0.99(4.39)
Change in FPGmmol/L · Week 0, week 26, week 52, week 78 · mean
MeasureOral Semaglutide 3 mgn=466Oral Semaglutide 7 mgn=465Oral Semaglutide 14 mgn=465Sitagliptin 100 mgn=467
Week 26-0.83(2.69)-1.17(2.54)-1.67(2.60)-0.90(2.32)
Week 52-0.98(2.78)-1.28(2.62)-1.75(2.57)-1.03(2.60)
Week 78-1.07(3.21)-1.11(2.92)-1.65(2.71)-0.91(2.59)
Change in BMIKg/m^2 · Week 0, week 26, week 52, week 78 · mean
MeasureOral Semaglutide 3 mgn=466Oral Semaglutide 7 mgn=465Oral Semaglutide 14 mgn=465Sitagliptin 100 mgn=467
Week 26-0.4(1.2)-0.8(1.4)-1.1(1.4)-0.2(1.1)
Week 52-0.6(1.5)-0.9(1.7)-1.2(1.7)-0.3(1.3)
Week 78-0.7(1.8)-1.0(1.9)-1.1(1.7)-0.4(1.5)
Change in Waist Circumferencecm · Week 0, week 26, week 52, week 78 · mean
MeasureOral Semaglutide 3 mgn=466Oral Semaglutide 7 mgn=465Oral Semaglutide 14 mgn=465Sitagliptin 100 mgn=467
Week 26-0.7(5.0)-1.8(5.2)-2.3(5.2)-0.6(4.4)
Week 52-1.3(5.7)-2.3(6.8)-2.6(6.2)-0.5(5.1)
Week 78-1.2(6.0)-2.4(7.2)-2.4(6.1)-0.7(5.6)
Change in Total Cholesterol (Ratio to Baseline)Ratio of total cholesterol · Week 0, week 26, week 52, week 78 · geometric mean
MeasureOral Semaglutide 3 mgn=466Oral Semaglutide 7 mgn=465Oral Semaglutide 14 mgn=465Sitagliptin 100 mgn=467
Week 261.00(16.8)0.98(17.5)0.97(17.1)1.00(16.4)
Week 521.00(17.5)0.99(18.5)0.98(17.0)1.01(16.9)
Week 781.00(18.3)0.99(19.3)0.99(18.7)1.00(19.4)
Change in LDL Cholesterol (Ratio to Baseline)Ratio of LDL cholesterol · Week 0, week 26, week 52, week 78 · geometric mean
MeasureOral Semaglutide 3 mgn=466Oral Semaglutide 7 mgn=465Oral Semaglutide 14 mgn=465Sitagliptin 100 mgn=467
Week 261.02(28.2)0.98(28.0)0.98(28.6)1.02(26.4)
Week 521.02(28.1)0.99(29.7)0.99(27.4)1.03(27.7)
Week 781.03(30.8)1.00(30.2)1.00(30.2)1.03(32.6)
Change in VLDL Cholesterol (Ratio to Baseline)Ratio of VLDL cholesterol · Week 0, week 26, week 52, week 78 · geometric mean
MeasureOral Semaglutide 3 mgn=466Oral Semaglutide 7 mgn=465Oral Semaglutide 14 mgn=465Sitagliptin 100 mgn=467
Week 260.99(36.4)0.96(36.1)0.91(36.3)0.97(34.1)
Week 521.00(35.0)0.98(39.1)0.93(39.6)0.98(34.4)
Week 780.95(41.7)0.94(41.5)0.91(40.4)0.94(39.6)
Change in HDL Cholesterol (Ratio to Baseline)Ratio of HDL cholesterol · Week 0, week 26, week 52, week 78 · geometric mean
MeasureOral Semaglutide 3 mgn=466Oral Semaglutide 7 mgn=465Oral Semaglutide 14 mgn=465Sitagliptin 100 mgn=467
Week 260.97(13.6)0.99(14.8)0.98(14.9)0.99(12.6)
Week 520.99(13.9)1.01(14.3)1.01(15.2)0.99(15.9)
Week 780.97(15.3)0.99(15.6)1.00(15.5)0.99(14.2)
Change in Triglycerides (Ratio to Baseline)Ratio of triglycerides · Week 0, week 26, week 52, week 78 · geometric mean
MeasureOral Semaglutide 3 mgn=466Oral Semaglutide 7 mgn=465Oral Semaglutide 14 mgn=465Sitagliptin 100 mgn=467
Week 260.99(38.1)0.96(39.2)0.92(39.8)0.97(36.2)
Week 521.00(35.7)0.97(41.3)0.93(42.3)0.98(37.8)
Week 780.95(43.9)0.94(43.7)0.92(43.1)0.93(41.6)
The trial

How PIONEER 3 was run

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.

  • Semaglutide 3 mg
  • Semaglutide 7 mg
  • Semaglutide 14 mg
  • Sitagliptin 100 mg
Who could join the trial

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)

Published papers

Papers from PIONEER 3

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

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