Phase 3 · Semaglutide

PIONEER 1 trial results

Efficacy and Safety of Oral Semaglutide Versus Placebo in Subjects With Type 2 Diabetes Mellitus Treated With Diet and Exercise Only.

Participants
703
Status
completed
Completed
2017-12-08
Sponsor
Novo Nordisk A/S

As posted on ClinicalTrials.gov (NCT02906930), 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 1 measured first

Change in HbA1cPercentage of HbA1c · Week 0, week 26 · mean
MeasureOral Semaglutide 3 mgn=175Oral Semaglutide 7 mgn=175Oral Semaglutide 14 mgn=175Placebon=178
In-trial-0.9(1.2)-1.3(1.0)-1.5(1.0)-0.3(1.2)
On-treatment without rescue medication-0.9(1.2)-1.4(0.9)-1.6(1.0)-0.3(1.2)
Side effects by arm

Side effects in PIONEER 1

Percent of participants affected, Week 0 to week 31 (26 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 mgPlacebo
Any serious event2.9%1.7%1.1%4.5%
Nausea8%5.1%16%5.6%
Diarrhoea8.6%5.1%5.1%2.2%
Vomiting2.9%4.6%6.9%2.2%
Nasopharyngitis5.7%6.3%1.7%3.4%
Headache3.4%5.7%5.1%5.1%
Decreased appetite1.1%1.7%5.1%0.6%
Influenza5.1%2.9%2.3%1.1%
Secondary outcomes

What else it measured

Change in Body Weight (kg)kg · Week 0, week 26 · mean
MeasureOral Semaglutide 3 mgn=175Oral Semaglutide 7 mgn=175Oral Semaglutide 14 mgn=175Placebon=178
In-trial-1.5(3.3)-2.6(4.1)-4.0(4.2)-1.4(3.5)
On-treatment without rescue medication-1.8(3.3)-2.8(4.0)-4.3(4.2)-1.6(3.6)
Change in Fasting Plasma Glucosemmol/L · Week 0, week 26 · mean
Oral Semaglutide 3 mgn=166Oral Semaglutide 7 mgn=160Oral Semaglutide 14 mgn=160Placebon=166
-0.89(2.67)-1.52(2.28)-1.92(2.04)-0.18(2.37)
Change in Mean 7-point SMPG Profilemmol/L · Week 0, week 26 · mean
Oral Semaglutide 3 mgn=149Oral Semaglutide 7 mgn=146Oral Semaglutide 14 mgn=141Placebon=147
-1.8(2.3)-2.1(2.0)-2.3(2.4)-0.5(2.6)
Change in Mean Postprandial Increment Over All Meals in SMPGmmol/L · Week 0, week 26 · mean
Oral Semaglutide 3 mgn=149Oral Semaglutide 7 mgn=148Oral Semaglutide 14 mgn=141Placebon=147
-0.4(2.3)-0.8(2.0)-1.2(2.1)-0.3(2.0)
Change in Fasting Insulin - Ratio to BaselineRatio of fasting insulin · Week 0, week 26 · geometric mean
Oral Semaglutide 3 mgn=157Oral Semaglutide 7 mgn=152Oral Semaglutide 14 mgn=159Placebon=163
1.12(59.2)1.07(49.2)0.98(45.0)0.97(59.2)
Change in Fasting Pro-insulin - Ratio to BaselineRatio of fasting pro-insulin · Week 0, week 26 · geometric mean
Oral Semaglutide 3 mgn=162Oral Semaglutide 7 mgn=158Oral Semaglutide 14 mgn=156Placebon=165
0.84(71.5)0.74(74.3)0.62(75.5)0.89(76.5)
Change in Fasting Glucagon - Ratio to BaselineRatio of fasting glucagon · Week 0, week 26 · geometric mean
Oral Semaglutide 3 mgn=161Oral Semaglutide 7 mgn=158Oral Semaglutide 14 mgn=159Placebon=163
1.00(28.2)0.90(27.1)0.89(25.7)0.95(25.4)
Change in HOMA-IR (Insulin Resistance) - Ratio to BaselineRatio of HOMA-IR · Week 0, week 26 · geometric mean
Oral Semaglutide 3 mgn=156Oral Semaglutide 7 mgn=152Oral Semaglutide 14 mgn=159Placebon=161
1.00(74.6)0.88(66.7)0.76(60.4)0.92(75.0)
Change in HOMA-B (Beta-cell Function) - Ratio to BaselineRatio of HOMA-B · Week 0, week 26 · geometric mean
Oral Semaglutide 3 mgn=156Oral Semaglutide 7 mgn=152Oral Semaglutide 14 mgn=159Placebon=160
1.40(73.2)1.51(60.5)1.60(58.4)1.01(61.9)
Change in CRP - Ratio to BaselineRatio of CRP · Week 0, week 26 · geometric mean
Oral Semaglutide 3 mgn=165Oral Semaglutide 7 mgn=159Oral Semaglutide 14 mgn=158Placebon=165
0.89(87.5)0.72(118.2)0.81(123.7)0.99(108.3)
Change in Body Weight (%)Percentage change · Week 0, week 26 · mean
Oral Semaglutide 3 mgn=168Oral Semaglutide 7 mgn=160Oral Semaglutide 14 mgn=160Placebon=168
-1.67(4.08)-2.85(4.57)-4.71(5.00)-1.37(3.58)
Change in BMIkg/m^2 · Week 0, week 26 · mean
Oral Semaglutide 3 mgn=168Oral Semaglutide 7 mgn=160Oral Semaglutide 14 mgn=160Placebon=168
-0.6(1.2)-0.9(1.5)-1.5(1.5)-0.5(1.2)
The trial

How PIONEER 1 was run

This trial is conducted globally. The aim of this trial is to investigate efficacy and safety of oral semaglutide versus placebo in subjects with type 2 diabetes mellitus treated with diet and exercise only.

  • 3 mg oral semaglutide
  • 7 mg oral semaglutide
  • 14 mg oral semaglutide
  • 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 above or equal to 20 years at the time of signing informed consent. For Algeria only: Male or female, age above or equal to 19 years at the time of signing informed consent - Diagnosed with type 2 diabetes mellitus for at least 30 days prior to day of screening - HbA1c (glycosylated haemoglobin) between 7.0-9.5% (53-80 mmol/mol) (both inclusive) - Treatment with diet and exercise for at least 30 days prior to 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 Japan only: Adequate contraceptive measures are abstinence (not having sex), diaphragm, condom (by the partner), intrauterine device, sponge, spermicide or oral contraceptives.For Czech Republic only: Adequate contraceptive measures are always one highly reliable method (such as intrauterine device, sterilisation of one of the partners, hormonal birth control methods) plus one supplementary barrier method (such as condom, diaphragm) with a spermicide. In justified cases, this combination may be replaced with a double-barrier method with a spermicide. Total sexual abstinence may also be considered contraception. (Please note: hormonal contraception should always be discussed with a gynaecologist) - 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 carcinomas - 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 and randomisation - 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 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 - Treatment with any medication for the indication of diabetes or obesity in a period of 90 days before the day of screening. An exception is short-term insulin treatment for acute illness for a...

Published papers

Papers from PIONEER 1

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

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