Phase 3 · Liraglutide

PIONEER 4 trial results

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

Participants
711
Status
completed
Completed
2018-03-30
Sponsor
Novo Nordisk A/S

As posted on ClinicalTrials.gov (NCT02863419), 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 4 measured first

Change in HbA1c (Week 26)Percentage of HbA1c · Week 0, week 26 · mean
MeasureOral Semaglutide 14 mgn=285Liraglutide 1.8 mgn=284Placebon=142
In-trial-1.2(0.9)-1.1(0.9)-0.1(0.7)
On-treatment without rescue medication-1.4(0.9)-1.2(0.9)-0.1(0.7)
Side effects by arm

Side effects in PIONEER 4

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 mgLiraglutide 1.8 mgPlacebo
Any serious event10.9%7.7%10.6%
Nausea19.3%18%3.5%
Diarrhoea15.1%10.9%7.7%
Nasopharyngitis14.4%13%10.6%
Headache9.5%6%5.6%
Vomiting8.4%4.6%2.1%
Constipation7.7%3.9%2.8%
Decreased appetite5.6%7%0%
Blood glucose increased0%0.7%6.3%
Back pain3.9%6%3.5%
Abdominal pain5.6%2.1%2.1%
Dyspepsia5.6%4.2%0%
Secondary outcomes

What else it measured

Change in Body Weight (Week 26)Kg · Week 0, week 26 · mean
MeasureOral Semaglutide 14 mgn=285Liraglutide 1.8 mgn=284Placebon=142
In-trial-4.4(4.4)-3.2(3.7)-0.6(3.1)
On-treatment without rescue medication-4.7(4.3)-3.3(3.7)-0.7(3.1)
Change in HbA1c (Week 52)Percentage of HbA1c · Week 0, week 52 · mean
Oral Semaglutide 14 mgn=275Liraglutide 1.8 mgn=269Placebon=133
-1.2(1.0)-0.9(1.0)-0.1(0.9)
Change in Body Weight (Week 52)Kg · Week 0, week 52 · mean
Oral Semaglutide 14 mgn=275Liraglutide 1.8 mgn=269Placebon=133
-4.4(5.5)-3.1(4.4)-1.0(3.8)
Change in Body Weight (%)Percentage change · Week 0, Week 26, Week 52 · mean
MeasureOral Semaglutide 14 mgn=285Liraglutide 1.8 mgn=284Placebon=142
Week 26-4.89(4.95)-3.33(3.78)-0.60(3.34)
Week 52-4.94(6.37)-3.25(4.33)-0.99(4.12)
Change in Fasting Plasma Glucosemmol/L · Week 0, week 26, week 52 · mean
MeasureOral Semaglutide 14 mgn=285Liraglutide 1.8 mgn=284Placebon=142
Week 26-2.04(2.28)-1.91(2.05)-0.33(2.03)
Week 52-1.91(2.41)-1.54(2.41)-0.66(1.99)
Change in Body Mass Indexkg/m^2 · Week 0, week 26, week 52 · mean
MeasureOral Semaglutide 14 mgn=285Liraglutide 1.8 mgn=284Placebon=142
Week 26-1.6(1.6)-1.1(1.3)-0.2(1.1)
Week 52-1.6(2.0)-1.1(1.5)-0.4(1.4)
Change in Waist Circumferencecm · Week 0, week 26, week 52 · mean
MeasureOral Semaglutide 14 mgn=285Liraglutide 1.8 mgn=284Placebon=142
Week 26-4.2(5.4)-3.0(4.5)-1.2(3.9)
Week 52-4.4(6.1)-2.7(5.1)-1.7(4.7)
Change in Total Cholesterol - Ratio to BaselineRatio of total cholesterol · Week 0, week 26, week 52 · geometric mean
MeasureOral Semaglutide 14 mgn=285Liraglutide 1.8 mgn=284Placebon=142
Week 260.96(20.3)0.97(21.6)0.99(17.0)
Week 520.98(20.5)0.98(19.6)1.02(18.3)
Change in Low-density Lipoprotein (LDL) Cholesterol - Ratio to BaselineRatio of LDL cholesterol · Week 0, week 26, week 52 · geometric mean
MeasureOral Semaglutide 14 mgn=285Liraglutide 1.8 mgn=284Placebon=142
Week 260.95(29.9)0.97(43.6)0.99(30.8)
Week 520.99(31.6)1.00(38.5)1.06(33.1)
Change in Very Low Density Lipoprotein (VLDL) Cholesterol - Ratio to BaselineRatio of VLDL cholesterol · Week 0, week 26, week 52 · geometric mean
MeasureOral Semaglutide 14 mgn=285Liraglutide 1.8 mgn=284Placebon=142
Week 260.90(43.5)0.91(37.1)1.02(29.4)
Week 520.87(41.9)0.90(37.5)0.98(39.8)
Change in High-density Lipoprotein (HDL) Cholesterol - Ratio to BaselineRatio of HDL-cholesterol · Week 0, week 26, week 52 · geometric mean
MeasureOral Semaglutide 14 mgn=285Liraglutide 1.8 mgn=284Placebon=142
Week 261.02(13.8)1.02(15.2)1.02(12.2)
Week 521.03(13.8)1.01(14.7)1.00(12.7)
Change in Triglycerides - Ratio to BaselineRatio of triglycerides · Week 0, week 26, week 52 · geometric mean
MeasureOral Semaglutide 14 mgn=285Liraglutide 1.8 mgn=284Placebon=142
Week 260.89(48.4)0.91(38.3)1.01(34.7)
Week 520.87(47.0)0.89(41.1)0.97(43.4)
The trial

How PIONEER 4 was run

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.

  • Oral Semaglutide
  • Liraglutide
  • Placebo
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. 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

Published papers

Papers from PIONEER 4

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

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