PIONEER 1

CompletedPhase 3Results posted

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

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

Lead sponsor

Novo Nordisk A/S

Asset

Semaglutide

Oral · GLP-1 agonist

Listed sites

105

Recruiting sites

—

Enrollment

703

actual

Study population

Type 2 diabetes

Key I/E criterion

•HbA1c 7-9.5%

Primary endpoint

•HbA1c, change

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT02906930

Org study IDNN9924-4233

Secondary ID2015-005622-19

Secondary IDJapicCTI-163384JapicCTI

Secondary IDU1111-1177-5112WHO

Timeline

Milestones

Study first posted2016-09-20estimated

Study start2016-09-20actual

Primary completion2017-10-30actual

Study completion2017-12-08actual

Results first posted2020-02-17actual

Last update posted2022-07-20actual

Assets

Investigational agents

Semaglutide

Study populations

Who this study enrolls

Type 2 diabetes

Eligibility

Who can enroll

Minimum age18 Years

SexAll

Healthy volunteersNot accepted

Eligibility 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 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 in-situ carcinomas)

Endpoints (96)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Glycemic / diabetes

Safety / tolerability / PK

Cardiometabolic biomarkers

Weight & body composition

Patient-reported / QoL

Other clinical outcomes

Other (unclassified)

Weight & body composition

12 endpoints

Secondary/registry result

Change in Body Weight (kg)

Time frame:Week 0, week 26

Body weight, absolute change (kg)

change from baseline, improvement

Posted result

Group	Value (mean), kg	95% CI
Oral Semaglutide 3 mgIn-trial	-1.5	—
On-treatment without rescue medication	-1.8	—
Oral Semaglutide 7 mgIn-trial	-2.6	—
On-treatment without rescue medication	-2.8	—
Oral Semaglutide 14 mgIn-trial	-4.0	—
On-treatment without rescue medication	-4.3	—
PlaceboIn-trial	-1.4	—
On-treatment without rescue medication	-1.6	—

Mean treatment difference-2.395% CI-3.1 – -1.5p<0.0001Pattern mixed model

Mean treatment difference-0.995% CI-1.9 – 0.1p0.0866Pattern mixed model

Mean treatment difference-0.195% CI-0.9 – 0.8p0.8692Pattern mixed model

Mean treatment difference-0.295% CI-1.0 – 0.6p0.7075MMRM

Mean treatment difference-1.095% CI-1.8 – -0.2p0.0138MMRM

Mean treatment difference-2.695% CI-3.4 – -1.8p<0.0001MMRM

Secondary/registry result

Change in Body Weight (%)

Time frame:Week 0, week 26

Body weight, % change

percent change from baseline, improvement

Posted result

Group	Value (mean), Percentage change	95% CI
Oral Semaglutide 3 mg	-1.67	—
Oral Semaglutide 7 mg	-2.85	—
Oral Semaglutide 14 mg	-4.71	—
Placebo	-1.37	—

Secondary/registry result

Change in BMI

Time frame:Week 0, week 26

BMI, change

change from baseline, improvement

Posted result

Group	Value (mean), kg/m^2	95% CI
Oral Semaglutide 3 mg	-0.6	—
Oral Semaglutide 7 mg	-0.9	—
Oral Semaglutide 14 mg	-1.5	—
Placebo	-0.5	—

Secondary/registry result

Change in Waist Circumference

Time frame:Week 0, week 26

Waist circumference, change

change from baseline, improvement

Posted result

Group	Value (mean), cm	95% CI
Oral Semaglutide 3 mg	-2.0	—
Oral Semaglutide 7 mg	-2.3	—
Oral Semaglutide 14 mg	-4.1	—
Placebo	-0.9	—

Secondary/registry result

Participants Who Achieve Body Weight Loss ≥ 5 % (Yes/no)

Time frame:Week 26

≥5% weight-loss responders

threshold achievement, improvement

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 3 mgYes	33	—
No	135	—
Oral Semaglutide 7 mgYes	43	—
No	117	—
Oral Semaglutide 14 mgYes	66	—
No	94	—
PlaceboYes	25	—
No	143	—

Secondary/registry result

Participants Who Achieve Body Weight Loss ≥ 10 % (Yes/no)

Time frame:Week 26

≥10% weight-loss responders

threshold achievement, improvement

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 3 mgYes	4	—
No	164	—
Oral Semaglutide 7 mgYes	13	—
No	147	—
Oral Semaglutide 14 mgYes	23	—
No	137	—
PlaceboYes	2	—
No	166	—

Secondary/protocol endpoint

Change in Body Weight (kg)

Time frame:Week 0, week 26

Body weight, absolute change (kg)

change from baseline, improvement

Secondary/protocol endpoint

Change in Body Weight (%)

Time frame:Week 0, week 26

Body weight, % change

percent change from baseline, improvement

Secondary/protocol endpoint

Change in BMI

Time frame:Week 0, week 26

BMI, change

change from baseline, improvement

Secondary/protocol endpoint

Change in Waist Circumference

Time frame:Week 0, week 26

Waist circumference, change

change from baseline, improvement

Secondary/protocol endpoint

Participants Who Achieve Body Weight Loss ≥ 5 % (Yes/no)

Time frame:Week 26

≥5% weight-loss responders

threshold achievement, improvement

Secondary/protocol endpoint

Participants Who Achieve Body Weight Loss ≥ 10 % (Yes/no)

Time frame:Week 26

≥10% weight-loss responders

threshold achievement, improvement

Glycemic / diabetes

29 endpoints

Primary/registry result

Change in HbA1c

Time frame:Week 0, week 26

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Posted result

Group	Value (mean), Percentage of HbA1c	95% CI
Oral Semaglutide 3 mgIn-trial	-0.9	—
On-treatment without rescue medication	-0.9	—
Oral Semaglutide 7 mgIn-trial	-1.3	—
On-treatment without rescue medication	-1.4	—
Oral Semaglutide 14 mgIn-trial	-1.5	—
On-treatment without rescue medication	-1.6	—
PlaceboIn-trial	-0.3	—
On-treatment without rescue medication	-0.3	—

Mean treatment difference-1.195% CI-1.3 – -0.9p<0.0001Pattern mixed model

Mean treatment difference-0.995% CI-1.1 – -0.6p<0.0001Pattern mixed model

Mean treatment difference-0.695% CI-0.8 – -0.4p<0.0001Pattern mixed model

Mean treatment difference-0.795% CI-0.9 – -0.5p<0.0001MMRM

Mean treatment difference-1.295% CI-1.5 – -1.0p<0.0001MMRM

Mean treatment difference-1.495% CI-1.7 – -1.2p<0.0001MMRM

Primary/protocol endpoint

Change in HbA1c

Time frame:Week 0, week 26

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Secondary/registry result

Change in Fasting Plasma Glucose

Time frame:Week 0, week 26

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Posted result

Group	Value (mean), mmol/L	95% CI
Oral Semaglutide 3 mg	-0.89	—
Oral Semaglutide 7 mg	-1.52	—
Oral Semaglutide 14 mg	-1.92	—
Placebo	-0.18	—

Secondary/registry result

Change in Mean 7-point SMPG Profile

Time frame:Week 0, week 26

Postprandial glucose

change from baseline, improvement

Posted result

Group	Value (mean), mmol/L	95% CI
Oral Semaglutide 3 mg	-1.8	—
Oral Semaglutide 7 mg	-2.1	—
Oral Semaglutide 14 mg	-2.3	—
Placebo	-0.5	—

Secondary/registry result

Change in Mean Postprandial Increment Over All Meals in SMPG

Time frame:Week 0, week 26

Postprandial glucose

change from baseline, improvement

Posted result

Group	Value (mean), mmol/L	95% CI
Oral Semaglutide 3 mg	-0.4	—
Oral Semaglutide 7 mg	-0.8	—
Oral Semaglutide 14 mg	-1.2	—
Placebo	-0.3	—

Secondary/registry result

Change in Fasting Insulin - Ratio to Baseline

Time frame:Week 0, week 26

ratio, improvement

Posted result

Group	Value (geometric_mean), Ratio of fasting insulin	95% CI
Oral Semaglutide 3 mg	1.12	—
Oral Semaglutide 7 mg	1.07	—
Oral Semaglutide 14 mg	0.98	—
Placebo	0.97	—

Secondary/registry result/low confidence

Change in Fasting Pro-insulin - Ratio to Baseline

Time frame:Week 0, week 26

ratio, improvement

Posted result

Group	Value (geometric_mean), Ratio of fasting pro-insulin	95% CI
Oral Semaglutide 3 mg	0.84	—
Oral Semaglutide 7 mg	0.74	—
Oral Semaglutide 14 mg	0.62	—
Placebo	0.89	—

Secondary/registry result

Change in Fasting Glucagon - Ratio to Baseline

Time frame:Week 0, week 26

ratio, improvement

Posted result

Group	Value (geometric_mean), Ratio of fasting glucagon	95% CI
Oral Semaglutide 3 mg	1.00	—
Oral Semaglutide 7 mg	0.90	—
Oral Semaglutide 14 mg	0.89	—
Placebo	0.95	—

Secondary/registry result

Change in HOMA-IR (Insulin Resistance) - Ratio to Baseline

Time frame:Week 0, week 26

HOMA-IR (insulin sensitivity)

ratio, improvement

Posted result

Group	Value (geometric_mean), Ratio of HOMA-IR	95% CI
Oral Semaglutide 3 mg	1.00	—
Oral Semaglutide 7 mg	0.88	—
Oral Semaglutide 14 mg	0.76	—
Placebo	0.92	—

Secondary/registry result

Change in HOMA-B (Beta-cell Function) - Ratio to Baseline

Time frame:Week 0, week 26

ratio, improvement

Posted result

Group	Value (geometric_mean), Ratio of HOMA-B	95% CI
Oral Semaglutide 3 mg	1.40	—
Oral Semaglutide 7 mg	1.51	—
Oral Semaglutide 14 mg	1.60	—
Placebo	1.01	—

Secondary/registry result

Participants Who Achieve HbA1c < 7.0 % (53 mmol/Mol) ADA Target (Yes/no)

Time frame:Week 26

HbA1c <7.0% achievement

threshold achievement, improvement

LOINC 4548-4

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 3 mgYes	92	—
No	75	—
Oral Semaglutide 7 mgYes	110	—
No	50	—
Oral Semaglutide 14 mgYes	123	—
No	37	—
PlaceboYes	52	—
No	116	—

Secondary/registry result

Participants Who Achieve HbA1c ≤ 6.5 % (48 mmol/Mol) AACE Target (Yes/no)

Time frame:Week 26

HbA1c <6.5% achievement

threshold achievement, improvement

LOINC 4548-4

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 3 mgYes	60	—
No	107	—
Oral Semaglutide 7 mgYes	76	—
No	84	—
Oral Semaglutide 14 mgYes	102	—
No	58	—
PlaceboYes	30	—
No	138	—

Secondary/registry result

Participants Who Achieve HbA1c < 7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG-confirmed Symptomatic Hypoglycaemia) and Without Body Weight Gain (Yes/no)

Time frame:Week 26

HbA1c <7.0% achievement

threshold achievement, improvement

componentsHbA1c <7.0% achievement, Severe hypoglycemia, Body weight, absolute change (kg)

LOINC 4548-4

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 3 mgYes	62	—
No	105	—
Oral Semaglutide 7 mgYes	91	—
No	69	—
Oral Semaglutide 14 mgYes	110	—
No	50	—
PlaceboYes	39	—
No	129	—

Secondary/registry result

Participants Who Achieve HbA1c Reduction ≥ 1.0% (10.9 mmol/Mol) and Weight Loss ≥ 3% (Yes/no)

Time frame:Week 26

threshold achievement, improvement

componentsHbA1c, change, Body weight, % change

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 3 mgYes	30	—
No	137	—
Oral Semaglutide 7 mgYes	59	—
No	101	—
Oral Semaglutide 14 mgYes	81	—
No	79	—
PlaceboYes	18	—
No	150	—

Secondary/registry result

Time to Additional Anti-diabetic Medication

Time frame:Weeks 0-26

threshold achievement, event

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 3 mg	16	—
Oral Semaglutide 7 mg	8	—
Oral Semaglutide 14 mg	7	—
Placebo	35	—

Hazard Ratio (HR)0.4595% CI0.26 – 0.78p0.0043Regression, Cox

Hazard Ratio (HR)0.3395% CI0.18 – 0.59p0.0002Regression, Cox

Hazard Ratio (HR)0.3395% CI0.19 – 0.60p0.0002Regression, Cox

Secondary/registry result

Time to Rescue Medication

Time frame:Weeks 0-26

threshold achievement, event

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 3 mg	13	—
Oral Semaglutide 7 mg	4	—
Oral Semaglutide 14 mg	2	—
Placebo	27	—

Hazard Ratio (HR)0.4895% CI0.25 – 0.93p0.0300Regression, Cox

Hazard Ratio (HR)0.1395% CI0.04 – 0.36p0.0001Regression, Cox

Hazard Ratio (HR)0.0695% CI0.01 – 0.26p0.0001Regression, Cox

Secondary/protocol endpoint

Change in Fasting Plasma Glucose

Time frame:Week 0, week 26

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Secondary/protocol endpoint

Change in Mean 7-point SMPG Profile

Time frame:Week 0, week 26

Postprandial glucose

change from baseline, improvement

Secondary/protocol endpoint

Change in Mean Postprandial Increment Over All Meals in SMPG

Time frame:Week 0, week 26

Postprandial glucose

change from baseline, improvement

Secondary/protocol endpoint

Change in Fasting Insulin - Ratio to Baseline

Time frame:Week 0, week 26

ratio, improvement

Secondary/protocol endpoint

Change in Fasting Pro-insulin - Ratio to Baseline

Time frame:Week 0, week 26

ratio, improvement

Secondary/protocol endpoint

Change in HOMA-IR (Insulin Resistance) - Ratio to Baseline

Time frame:Week 0, week 26

HOMA-IR (insulin sensitivity)

ratio, improvement

Secondary/protocol endpoint

Change in HOMA-B (Beta-cell Function) - Ratio to Baseline

Time frame:Week 0, week 26

ratio, improvement

Secondary/protocol endpoint

Participants Who Achieve HbA1c < 7.0 % (53 mmol/Mol) ADA Target (Yes/no)

Time frame:Week 26

HbA1c <7.0% achievement

threshold achievement, improvement

LOINC 4548-4

Secondary/protocol endpoint

Participants Who Achieve HbA1c ≤ 6.5 % (48 mmol/Mol) AACE Target (Yes/no)

Time frame:Week 26

HbA1c <6.5% achievement

threshold achievement, improvement

LOINC 4548-4

Secondary/protocol endpoint

Participants Who Achieve HbA1c < 7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG-confirmed Symptomatic Hypoglycaemia) and Without Body Weight Gain (Yes/no)

Time frame:Week 26

HbA1c <7.0% achievement

threshold achievement, improvement

LOINC 4548-4

Secondary/protocol endpoint

Participants Who Achieve HbA1c Reduction ≥ 1.0% (10.9 mmol/Mol) and Weight Loss ≥ 3% (Yes/no)

Time frame:Week 26

threshold achievement, improvement

componentsHbA1c, change, Body weight, % change

Secondary/protocol endpoint

Time to Additional Anti-diabetic Medication

Time frame:Weeks 0-26

event count, event

Secondary/protocol endpoint/low confidence

Time to Rescue Medication

Time frame:Weeks 0-26

time to event, event

Cardiometabolic biomarkers

16 endpoints

Secondary/registry result

Change in CRP - Ratio to Baseline

Time frame:Week 0, week 26

hs-CRP, change

ratio, improvement

LOINC 30522-7

Posted result

Group	Value (geometric_mean), Ratio of CRP	95% CI
Oral Semaglutide 3 mg	0.89	—
Oral Semaglutide 7 mg	0.72	—
Oral Semaglutide 14 mg	0.81	—
Placebo	0.99	—

Secondary/registry result

Change in Fasting Total Cholesterol - Ratio to Baseline

Time frame:Week 0, week 26

Total cholesterol, change

ratio, improvement

LOINC 2093-3

Posted result

Group	Value (geometric_mean), Ratio of fasting total cholesterol	95% CI
Oral Semaglutide 3 mg	0.98	—
Oral Semaglutide 7 mg	0.98	—
Oral Semaglutide 14 mg	0.96	—
Placebo	1.01	—

Secondary/registry result

Change in Fasting LDL Cholesterol - Ratio to Baseline

Time frame:Week 0, week 26

LDL-C, change

ratio, improvement

LOINC 13457-7

Posted result

Group	Value (geometric_mean), Ratio of fasting LDL cholesterol	95% CI
Oral Semaglutide 3 mg	0.95	—
Oral Semaglutide 7 mg	0.97	—
Oral Semaglutide 14 mg	0.95	—
Placebo	1.00	—

Secondary/registry result

Change in Fasting HDL Cholesterol - Ratio to Baseline

Time frame:Week 0, week 26

HDL-C, change

ratio, improvement

LOINC 2085-9

Posted result

Group	Value (geometric_mean), Ratio of fasting HDL cholesterol	95% CI
Oral Semaglutide 3 mg	1.03	—
Oral Semaglutide 7 mg	1.05	—
Oral Semaglutide 14 mg	1.02	—
Placebo	1.03	—

Secondary/registry result

Change in Fasting Triglycerides - Ratio to Baseline

Time frame:Week 0, week 26

Triglycerides, change

ratio, improvement

LOINC 2571-8

Posted result

Group	Value (geometric_mean), Ratio of fasting triglycerides	95% CI
Oral Semaglutide 3 mg	1.01	—
Oral Semaglutide 7 mg	0.90	—
Oral Semaglutide 14 mg	0.91	—
Placebo	1.00	—

Secondary/registry result

Change in Pulse Rate

Time frame:Week 0, week 26

Heart rate, change

change from baseline, improvement

Posted result

Group	Value (mean), beats/min	95% CI
Oral Semaglutide 3 mg	0	—
Oral Semaglutide 7 mg	1	—
Oral Semaglutide 14 mg	3	—
Placebo	1	—

Secondary/registry result

Change in Systolic Blood Pressure (SBP)

Time frame:Week 0, week 26

Systolic BP, change

change from baseline, improvement

LOINC 8480-6

Posted result

Group	Value (mean), mmHg	95% CI
Oral Semaglutide 3 mg	-3	—
Oral Semaglutide 7 mg	-5	—
Oral Semaglutide 14 mg	-5	—
Placebo	-3	—

Secondary/registry result

Change in Diastolic Blood Pressure (DBP)

Time frame:Week 0, week 26

Diastolic BP, change

change from baseline, improvement

LOINC 8462-4

Posted result

Group	Value (mean), mmHg	95% CI
Oral Semaglutide 3 mg	-1	—
Oral Semaglutide 7 mg	-2	—
Oral Semaglutide 14 mg	-1	—
Placebo	-1	—

Secondary/protocol endpoint

Change in CRP - Ratio to Baseline

Time frame:Week 0, week 26

hs-CRP, change

ratio, improvement

LOINC 30522-7

Secondary/protocol endpoint

Change in Fasting Total Cholesterol - Ratio to Baseline

Time frame:Week 0, week 26

Total cholesterol, change

ratio, improvement

LOINC 2093-3

Secondary/protocol endpoint

Change in Fasting LDL Cholesterol - Ratio to Baseline

Time frame:Week 0, week 26

LDL-C, change

ratio, improvement

LOINC 13457-7

Secondary/protocol endpoint

Change in Fasting HDL Cholesterol - Ratio to Baseline

Time frame:Week 0, week 26

HDL-C, change

ratio, improvement

LOINC 2085-9

Secondary/protocol endpoint

Change in Fasting Triglycerides - Ratio to Baseline

Time frame:Week 0, week 26

Triglycerides, change

ratio, improvement

LOINC 2571-8

Secondary/protocol endpoint

Change in Pulse Rate

Time frame:Week 0, week 26

Heart rate, change

change from baseline, improvement

Secondary/protocol endpoint

Change in Systolic Blood Pressure (SBP)

Time frame:Week 0, week 26

Systolic BP, change

change from baseline, improvement

LOINC 8480-6

Secondary/protocol endpoint

Change in Diastolic Blood Pressure (DBP)

Time frame:Week 0, week 26

Diastolic BP, change

change from baseline, improvement

LOINC 8462-4

Patient-reported / QoL

8 endpoints

Secondary/registry result

Change in SF-36v2 (Acute Version) Health Survey: Scores From the 8 Domains, the Physical Component Summary (PCS) and the Mental Component Summary (MCS)

Time frame:Week 0, week 26

SF-36 total

change from baseline, improvement

Posted result

Group	Value (mean), Score on a scale	95% CI
Oral Semaglutide 3 mg1) Physical Functioning	0.14	—
2) Role-Physical	-0.41	—
3) Bodily Pain	1.17	—
4) General Health	0.97	—
5) Vitality	-0.08	—
6) Social Functioning	0.21	—
7) Role-Emotional	-0.05	—
8) Mental Health	0.04	—
Physical component summary	0.52	—
Mental component summary	-0.07	—
Oral Semaglutide 7 mg1) Physical Functioning	1.18	—
2) Role-Physical	-0.08	—
3) Bodily Pain	-0.67	—
4) General Health	0.92	—
5) Vitality	0.77	—
6) Social Functioning	1.00	—
7) Role-Emotional	-0.63	—
8) Mental Health	0.06	—
Physical component summary	0.61	—
Mental component summary	-0.00	—
Oral Semaglutide 14 mg1) Physical Functioning	1.05	—
2) Role-Physical	0.79	—
3) Bodily Pain	-0.14	—
4) General Health	2.07	—
5) Vitality	0.40	—
6) Social Functioning	0.88	—
7) Role-Emotional	0.85	—
8) Mental Health	0.67	—
Physical component summary	0.89	—
Mental component summary	0.67	—
Placebo1) Physical Functioning	0.66	—
2) Role-Physical	-0.25	—
3) Bodily Pain	0.40	—
4) General Health	0.18	—
5) Vitality	-0.47	—
6) Social Functioning	0.18	—
7) Role-Emotional	-1.28	—
8) Mental Health	-0.25	—
Physical component summary	0.65	—
Mental component summary	-0.90	—

Secondary/registry result

IWQOL-Lite Clinical Trial Version: Total Score of the 22 Items (Used for Validation of the Questionnaire)

Time frame:Week 0, week 26

IWQOL-Lite total

change from baseline, improvement

Posted result

Group	Value (mean), Score on a scale	95% CI
Oral Semaglutide 3 mg1) Trouble bending over	-0.17	—
2) Tired/winded walking up stairs	-0.13	—
3) Difficulty standing	-0.12	—
4) Uncomfortable in small seats	-0.09	—
5) Bodily pain	-0.27	—
6) Self-conscious eating in social settings	0.00	—
7) Less confident	-0.22	—
8) Feel judged by others	-0.01	—
9) Less important/worthy of respect	-0.05	—
10) Frustrated shopping for clothes	-0.08	—
11) Feel bad or upset in pictures	-0.16	—
12) Feel down or depressed	-0.22	—
13) Less interested in sex	-0.14	—
14) Avoid social gatherings	0.05	—
15) Less productive	-0.09	—
16) Lack energy to do things I would like to do	-0.14	—
17) Not as physically active	-0.09	—
18) Unable to walk far/quickly	-0.08	—
19) Worried about health	-0.32	—
20) Limited self-esteem	-0.03	—
21) Self-conscious about weight	-0.10	—
22) Frustrated/upset with self	-0.12	—
Oral Semaglutide 7 mg1) Trouble bending over	-0.12	—
2) Tired/winded walking up stairs	-0.16	—
3) Difficulty standing	-0.22	—
4) Uncomfortable in small seats	-0.05	—
5) Bodily pain	-0.08	—
6) Self-conscious eating in social settings	0.01	—
7) Less confident	-0.29	—
8) Feel judged by others	-0.23	—
9) Less important/worthy of respect	-0.04	—
10) Frustrated shopping for clothes	-0.10	—
11) Feel bad or upset in pictures	-0.20	—
12) Feel down or depressed	-0.18	—
13) Less interested in sex	0.04	—
14) Avoid social gatherings	-0.07	—
15) Less productive	-0.13	—
16) Lack energy to do things I would like to do	-0.20	—
17) Not as physically active	-0.41	—
18) Unable to walk far/quickly	-0.29	—
19) Worried about health	-0.49	—
20) Limited self-esteem	-0.09	—
21) Self-conscious about weight	-0.12	—
22) Frustrated/upset with self	-0.25	—
Oral Semaglutide 14 mg1) Trouble bending over	-0.13	—
2) Tired/winded walking up stairs	-0.23	—
3) Difficulty standing	-0.08	—
4) Uncomfortable in small seats	-0.09	—
5) Bodily pain	-0.06	—
6) Self-conscious eating in social settings	-0.11	—
7) Less confident	-0.35	—
8) Feel judged by others	-0.20	—
9) Less important/worthy of respect	-0.11	—
10) Frustrated shopping for clothes	-0.19	—
11) Feel bad or upset in pictures	-0.23	—
12) Feel down or depressed	-0.24	—
13) Less interested in sex	-0.03	—
14) Avoid social gatherings	-0.04	—
15) Less productive	-0.10	—
16) Lack energy to do things I would like to do	-0.14	—
17) Not as physically active	-0.04	—
18) Unable to walk far/quickly	0.02	—
19) Worried about health	-0.42	—
20) Limited self-esteem	-0.07	—
21) Self-conscious about weight	0.01	—
22) Frustrated/upset with self	-0.14	—
Placebo1) Trouble bending over	-0.08	—
2) Tired/winded walking up stairs	-0.11	—
3) Difficulty standing	-0.01	—
4) Uncomfortable in small seats	0.03	—
5) Bodily pain	-0.14	—
6) Self-conscious eating in social settings	-0.10	—
7) Less confident	-0.20	—
8) Feel judged by others	-0.13	—
9) Less important/worthy of respect	-0.15	—
10) Frustrated shopping for clothes	-0.14	—
11) Feel bad or upset in pictures	-0.14	—
12) Feel down or depressed	-0.16	—
13) Less interested in sex	-0.06	—
14) Avoid social gatherings	-0.02	—
15) Less productive	-0.07	—
16) Lack energy to do things I would like to do	-0.03	—
17) Not as physically active	-0.08	—
18) Unable to walk far/quickly	-0.19	—
19) Worried about health	-0.30	—
20) Limited self-esteem	-0.09	—
21) Self-conscious about weight	-0.05	—
22) Frustrated/upset with self	0.02	—

Secondary/registry result

PGI-S Item: Scores of the Two Individual Items (Used for Validation of the IWQOL Questionnaire)

Time frame:Week 26

PGI, change

descriptive, improvement

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 3 mg1) Physical functioning status	6	—
1) Physical functioning status	50	—
1) Physical functioning status	67	—
1) Physical functioning status	30	—
1) Physical functioning status	14	—
2) Emotional status	10	—
2) Emotional status	41	—
2) Emotional status	62	—
2) Emotional status	32	—
2) Emotional status	22	—
Oral Semaglutide 7 mg1) Physical functioning status	11	—
1) Physical functioning status	51	—
1) Physical functioning status	53	—
1) Physical functioning status	38	—
1) Physical functioning status	4	—
2) Emotional status	7	—
2) Emotional status	41	—
2) Emotional status	51	—
2) Emotional status	48	—
2) Emotional status	11	—
Oral Semaglutide 14 mg1) Physical functioning status	11	—
1) Physical functioning status	45	—
1) Physical functioning status	56	—
1) Physical functioning status	32	—
1) Physical functioning status	15	—
2) Emotional status	9	—
2) Emotional status	38	—
2) Emotional status	55	—
2) Emotional status	33	—
2) Emotional status	24	—
Placebo1) Physical functioning status	7	—
1) Physical functioning status	59	—
1) Physical functioning status	71	—
1) Physical functioning status	23	—
1) Physical functioning status	7	—
2) Emotional status	9	—
2) Emotional status	42	—
2) Emotional status	59	—
2) Emotional status	41	—
2) Emotional status	15	—

Secondary/registry result

PGI-C Item: Scores of the Two Individual Items (Used for Validation of the IWQOL Questionnaire)

Time frame:Week 26

PGI, change

threshold achievement, improvement

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 3 mg1) Physical functioning change	0	—
1) Physical functioning change	1	—
1) Physical functioning change	6	—
1) Physical functioning change	56	—
1) Physical functioning change	45	—
1) Physical functioning change	23	—
1) Physical functioning change	36	—
2) Emotional change	1	—
2) Emotional change	0	—
2) Emotional change	5	—
2) Emotional change	60	—
2) Emotional change	38	—
2) Emotional change	18	—
2) Emotional change	45	—
Oral Semaglutide 7 mg1) Physical functioning change	0	—
1) Physical functioning change	2	—
1) Physical functioning change	2	—
1) Physical functioning change	44	—
1) Physical functioning change	42	—
1) Physical functioning change	28	—
1) Physical functioning change	40	—
2) Emotional change	0	—
2) Emotional change	0	—
2) Emotional change	2	—
2) Emotional change	53	—
2) Emotional change	32	—
2) Emotional change	27	—
2) Emotional change	44	—
Oral Semaglutide 14 mg1) Physical functioning change	1	—
1) Physical functioning change	0	—
1) Physical functioning change	3	—
1) Physical functioning change	29	—
1) Physical functioning change	48	—
1) Physical functioning change	31	—
1) Physical functioning change	47	—
2) Emotional change	1	—
2) Emotional change	0	—
2) Emotional change	3	—
2) Emotional change	36	—
2) Emotional change	37	—
2) Emotional change	32	—
2) Emotional change	50	—
Placebo1) Physical functioning change	1	—
1) Physical functioning change	1	—
1) Physical functioning change	3	—
1) Physical functioning change	66	—
1) Physical functioning change	36	—
1) Physical functioning change	31	—
1) Physical functioning change	29	—
2) Emotional change	0	—
2) Emotional change	1	—
2) Emotional change	2	—
2) Emotional change	63	—
2) Emotional change	39	—
2) Emotional change	32	—
2) Emotional change	30	—

Secondary/protocol endpoint

Change in SF-36v2 (Acute Version) Health Survey: Scores From the 8 Domains, the Physical Component Summary (PCS) and the Mental Component Summary (MCS)

Time frame:Week 0, week 26

SF-36 total

change from baseline, improvement

Secondary/protocol endpoint

IWQOL-Lite Clinical Trial Version: Total Score of the 22 Items (Used for Validation of the Questionnaire)

Time frame:Week 0, week 26

IWQOL-Lite total

change from baseline, improvement

Secondary/protocol endpoint

PGI-S Item: Scores of the Two Individual Items (Used for Validation of the IWQOL Questionnaire)

Time frame:Week 26

PGI, change

change from baseline, improvement

Secondary/protocol endpoint

PGI-C Item: Scores of the Two Individual Items (Used for Validation of the IWQOL Questionnaire)

Time frame:Week 26

PGI, change

change from baseline, improvement

Safety / tolerability / PK

28 endpoints

Secondary/registry result

Number of Treatment-emergent Adverse Events (TEAEs)

Time frame:Approximately upto week 31

Treatment-emergent AEs (any)

event count, event

Posted result

Group	Value (number), Events	95% CI
Oral Semaglutide 3 mg	290	—
Oral Semaglutide 7 mg	258	—
Oral Semaglutide 14 mg	304	—
Placebo	263	—

Secondary/registry result

Change in Amylase - Ratio to Baseline

Time frame:Week 0, week 26

ratio, descriptive

Posted result

Group	Value (geometric_mean), Ratio	95% CI
Oral Semaglutide 3 mg	1.05	—
Oral Semaglutide 7 mg	1.09	—
Oral Semaglutide 14 mg	1.12	—
Placebo	0.99	—

Secondary/registry result

Change in Lipase - Ratio to Baseline

Time frame:Week 0, week 26

ratio, descriptive

Posted result

Group	Value (geometric_mean), Ratio	95% CI
Oral Semaglutide 3 mg	1.14	—
Oral Semaglutide 7 mg	1.27	—
Oral Semaglutide 14 mg	1.33	—
Placebo	0.99	—

Secondary/registry result

Change in Electrocardiogram (ECG) Evaluation

Time frame:Week 0, week 26

categorical status, descriptive

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 3 mgNormal (week 0) to normal (week 26)	102	—
Normal (week 0) to abnormal NCS (week 26)	11	—
Normal (week 0) to abnormal CS (week 26)	1	—
Abnormal NCS (week 0) to normal (week 26)	12	—
Abnormal NCS (week 0) to abnormal NCS (week 26)	40	—
Abnormal NCS (week 0) to abnormal CS (week 26)	0	—
Abnormal CS (week 0) to normal (week 26)	0	—
Abnormal CS (week 0) to abnormal NCS (week 26)	1	—
Abnormal CS (week 0) to abnormal CS (week 26)	0	—
Oral Semaglutide 7 mgNormal (week 0) to normal (week 26)	88	—
Normal (week 0) to abnormal NCS (week 26)	13	—
Normal (week 0) to abnormal CS (week 26)	1	—
Abnormal NCS (week 0) to normal (week 26)	12	—
Abnormal NCS (week 0) to abnormal NCS (week 26)	39	—
Abnormal NCS (week 0) to abnormal CS (week 26)	1	—
Abnormal CS (week 0) to normal (week 26)	1	—
Abnormal CS (week 0) to abnormal NCS (week 26)	3	—
Abnormal CS (week 0) to abnormal CS (week 26)	1	—
Oral Semaglutide 14 mgNormal (week 0) to normal (week 26)	96	—
Normal (week 0) to abnormal NCS (week 26)	4	—
Normal (week 0) to abnormal CS (week 26)	0	—
Abnormal NCS (week 0) to normal (week 26)	20	—
Abnormal NCS (week 0) to abnormal NCS (week 26)	39	—
Abnormal NCS (week 0) to abnormal CS (week 26)	0	—
Abnormal CS (week 0) to normal (week 26)	0	—
Abnormal CS (week 0) to abnormal NCS (week 26)	0	—
Abnormal CS (week 0) to abnormal CS (week 26)	0	—
PlaceboNormal (week 0) to normal (week 26)	97	—
Normal (week 0) to abnormal NCS (week 26)	13	—
Normal (week 0) to abnormal CS (week 26)	0	—
Abnormal NCS (week 0) to normal (week 26)	14	—
Abnormal NCS (week 0) to abnormal NCS (week 26)	40	—
Abnormal NCS (week 0) to abnormal CS (week 26)	0	—
Abnormal CS (week 0) to normal (week 26)	0	—
Abnormal CS (week 0) to abnormal NCS (week 26)	2	—
Abnormal CS (week 0) to abnormal CS (week 26)	0	—

Secondary/registry result

Change in Physical Examination

Time frame:Week 0, week 26

descriptive

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 3 mg1) Cardiovascular system (week -2)	163	—
1) Cardiovascular system (week -2)	12	—
1) Cardiovascular system (week -2)	0	—
1) Cardiovascular system (week 26)	157	—
1) Cardiovascular system (week 26)	10	—
1) Cardiovascular system (week 26)	0	—
2) Central and peripheral nervous system (week -2)	165	—
2) Central and peripheral nervous system (week -2)	10	—
2) Central and peripheral nervous system (week -2)	0	—
2) Central and peripheral nervous system (week 26)	157	—
2) Central and peripheral nervous system (week 26)	10	—
2) Central and peripheral nervous system (week 26)	0	—
3) Gastrointestinal system, incl. mouth (week -2)	164	—
3) Gastrointestinal system, incl. mouth (week -2)	11	—
3) Gastrointestinal system, incl. mouth (week -2)	0	—
3) Gastrointestinal system, incl. mouth (week 26)	153	—
3) Gastrointestinal system, incl. mouth (week 26)	13	—
3) Gastrointestinal system, incl. mouth (week 26)	1	—
4) General appearance (week -2)	143	—
4) General appearance (week -2)	32	—
4) General appearance (week -2)	0	—
4) General appearance (week 26)	138	—
4) General appearance (week 26)	29	—
4) General appearance (week 26)	0	—
5) Head, ears, eyes, nose, throat, neck (week -2)	163	—
5) Head, ears, eyes, nose, throat, neck (week -2)	12	—
5) Head, ears, eyes, nose, throat, neck (week -2)	0	—
5) Head, ears, eyes, nose, throat, neck (week 26)	155	—
5) Head, ears, eyes, nose, throat, neck (week 26)	12	—
5) Head, ears, eyes, nose, throat, neck (week 26)	0	—
6) Lymph node palpation (week -2)	175	—
6) Lymph node palpation (week -2)	0	—
6) Lymph node palpation (week -2)	0	—
6) Lymph node palpation (week 26)	167	—
6) Lymph node palpation (week 26)	0	—
6) Lymph node palpation (week 26)	0	—
7) Musculoskeletal system (week -2)	164	—
7) Musculoskeletal system (week -2)	11	—
7) Musculoskeletal system (week -2)	0	—
7) Musculoskeletal system (week 26)	155	—
7) Musculoskeletal system (week 26)	11	—
7) Musculoskeletal system (week 26)	1	—
8) Respiratory system (week -2)	173	—
8) Respiratory system (week -2)	2	—
8) Respiratory system (week -2)	0	—
8) Respiratory system (week 26)	163	—
8) Respiratory system (week 26)	4	—
8) Respiratory system (week 26)	0	—
9) Skin (week -2)	137	—
9) Skin (week -2)	36	—
9) Skin (week -2)	2	—
9) Skin (week 26)	136	—
9) Skin (week 26)	30	—
9) Skin (week 26)	1	—
10) Thyroid gland (week -2)	173	—
10) Thyroid gland (week -2)	1	—
10) Thyroid gland (week -2)	1	—
10) Thyroid gland (week 26)	165	—
10) Thyroid gland (week 26)	1	—
10) Thyroid gland (week 26)	1	—
Oral Semaglutide 7 mg1) Cardiovascular system (week -2)	167	—
1) Cardiovascular system (week -2)	8	—
1) Cardiovascular system (week -2)	0	—
1) Cardiovascular system (week 26)	149	—
1) Cardiovascular system (week 26)	9	—
1) Cardiovascular system (week 26)	1	—
2) Central and peripheral nervous system (week -2)	171	—
2) Central and peripheral nervous system (week -2)	4	—
2) Central and peripheral nervous system (week -2)	0	—
2) Central and peripheral nervous system (week 26)	157	—
2) Central and peripheral nervous system (week 26)	2	—
2) Central and peripheral nervous system (week 26)	0	—
3) Gastrointestinal system, incl. mouth (week -2)	169	—
3) Gastrointestinal system, incl. mouth (week -2)	6	—
3) Gastrointestinal system, incl. mouth (week -2)	0	—
3) Gastrointestinal system, incl. mouth (week 26)	154	—
3) Gastrointestinal system, incl. mouth (week 26)	5	—
3) Gastrointestinal system, incl. mouth (week 26)	0	—
4) General appearance (week -2)	152	—
4) General appearance (week -2)	23	—
4) General appearance (week -2)	0	—
4) General appearance (week 26)	141	—
4) General appearance (week 26)	17	—
4) General appearance (week 26)	1	—
5) Head, ears, eyes, nose, throat, neck (week -2)	165	—
5) Head, ears, eyes, nose, throat, neck (week -2)	10	—
5) Head, ears, eyes, nose, throat, neck (week -2)	0	—
5) Head, ears, eyes, nose, throat, neck (week 26)	149	—
5) Head, ears, eyes, nose, throat, neck (week 26)	10	—
5) Head, ears, eyes, nose, throat, neck (week 26)	0	—
6) Lymph node palpation (week -2)	175	—
6) Lymph node palpation (week -2)	0	—
6) Lymph node palpation (week -2)	0	—
6) Lymph node palpation (week 26)	159	—
6) Lymph node palpation (week 26)	0	—
6) Lymph node palpation (week 26)	0	—
7) Musculoskeletal system (week -2)	169	—
7) Musculoskeletal system (week -2)	6	—
7) Musculoskeletal system (week -2)	0	—
7) Musculoskeletal system (week 26)	154	—
7) Musculoskeletal system (week 26)	5	—
7) Musculoskeletal system (week 26)	0	—
8) Respiratory system (week -2)	172	—
8) Respiratory system (week -2)	3	—
8) Respiratory system (week -2)	0	—
8) Respiratory system (week 26)	157	—
8) Respiratory system (week 26)	2	—
8) Respiratory system (week 26)	0	—
9) Skin (week -2)	156	—
9) Skin (week -2)	18	—
9) Skin (week -2)	1	—
9) Skin (week 26)	145	—
9) Skin (week 26)	13	—
9) Skin (week 26)	1	—
10) Thyroid gland (week -2)	170	—
10) Thyroid gland (week -2)	4	—
10) Thyroid gland (week -2)	1	—
10) Thyroid gland (week 26)	155	—
10) Thyroid gland (week 26)	4	—
10) Thyroid gland (week 26)	0	—
Oral Semaglutide 14 mg1) Cardiovascular system (week -2)	167	—
1) Cardiovascular system (week -2)	8	—
1) Cardiovascular system (week -2)	0	—
1) Cardiovascular system (week 26)	155	—
1) Cardiovascular system (week 26)	4	—
1) Cardiovascular system (week 26)	0	—
2) Central and peripheral nervous system (week -2)	168	—
2) Central and peripheral nervous system (week -2)	7	—
2) Central and peripheral nervous system (week -2)	0	—
2) Central and peripheral nervous system (week 26)	153	—
2) Central and peripheral nervous system (week 26)	6	—
2) Central and peripheral nervous system (week 26)	0	—
3) Gastrointestinal system, incl. mouth (week -2)	159	—
3) Gastrointestinal system, incl. mouth (week -2)	16	—
3) Gastrointestinal system, incl. mouth (week -2)	0	—
3) Gastrointestinal system, incl. mouth (week 26)	148	—
3) Gastrointestinal system, incl. mouth (week 26)	11	—
3) Gastrointestinal system, incl. mouth (week 26)	0	—
4) General appearance (week -2)	153	—
4) General appearance (week -2)	20	—
4) General appearance (week -2)	2	—
4) General appearance (week 26)	141	—
4) General appearance (week 26)	17	—
4) General appearance (week 26)	1	—
5) Head, ears, eyes, nose, throat, neck (week -2)	165	—
5) Head, ears, eyes, nose, throat, neck (week -2)	10	—
5) Head, ears, eyes, nose, throat, neck (week -2)	0	—
5) Head, ears, eyes, nose, throat, neck (week 26)	149	—
5) Head, ears, eyes, nose, throat, neck (week 26)	10	—
5) Head, ears, eyes, nose, throat, neck (week 26)	0	—
6) Lymph node palpation (week -2)	175	—
6) Lymph node palpation (week -2)	0	—
6) Lymph node palpation (week -2)	0	—
6) Lymph node palpation (week 26)	159	—
6) Lymph node palpation (week 26)	0	—
6) Lymph node palpation (week 26)	0	—
7) Musculoskeletal system (week -2)	167	—
7) Musculoskeletal system (week -2)	8	—
7) Musculoskeletal system (week -2)	0	—
7) Musculoskeletal system (week 26)	152	—
7) Musculoskeletal system (week 26)	6	—
7) Musculoskeletal system (week 26)	1	—
8) Respiratory system (week -2)	173	—
8) Respiratory system (week -2)	2	—
8) Respiratory system (week -2)	0	—
8) Respiratory system (week 26)	159	—
8) Respiratory system (week 26)	0	—
8) Respiratory system (week 26)	0	—
9) Skin (week -2)	150	—
9) Skin (week -2)	24	—
9) Skin (week -2)	1	—
9) Skin (week 26)	140	—
9) Skin (week 26)	18	—
9) Skin (week 26)	1	—
10) Thyroid gland (week -2)	169	—
10) Thyroid gland (week -2)	6	—
10) Thyroid gland (week -2)	0	—
10) Thyroid gland (week 26)	156	—
10) Thyroid gland (week 26)	3	—
10) Thyroid gland (week 26)	0	—
Placebo1) Cardiovascular system (week -2)	172	—
1) Cardiovascular system (week -2)	6	—
1) Cardiovascular system (week -2)	0	—
1) Cardiovascular system (week 26)	162	—
1) Cardiovascular system (week 26)	4	—
1) Cardiovascular system (week 26)	1	—
2) Central and peripheral nervous system (week -2)	169	—
2) Central and peripheral nervous system (week -2)	9	—
2) Central and peripheral nervous system (week -2)	0	—
2) Central and peripheral nervous system (week 26)	159	—
2) Central and peripheral nervous system (week 26)	8	—
2) Central and peripheral nervous system (week 26)	0	—
3) Gastrointestinal system, incl. mouth (week -2)	168	—
3) Gastrointestinal system, incl. mouth (week -2)	10	—
3) Gastrointestinal system, incl. mouth (week -2)	0	—
3) Gastrointestinal system, incl. mouth (week 26)	157	—
3) Gastrointestinal system, incl. mouth (week 26)	10	—
3) Gastrointestinal system, incl. mouth (week 26)	0	—
4) General appearance (week -2)	157	—
4) General appearance (week -2)	21	—
4) General appearance (week -2)	0	—
4) General appearance (week 26)	148	—
4) General appearance (week 26)	19	—
4) General appearance (week 26)	0	—
5) Head, ears, eyes, nose, throat, neck (week -2)	168	—
5) Head, ears, eyes, nose, throat, neck (week -2)	9	—
5) Head, ears, eyes, nose, throat, neck (week -2)	1	—
5) Head, ears, eyes, nose, throat, neck (week 26)	155	—
5) Head, ears, eyes, nose, throat, neck (week 26)	11	—
5) Head, ears, eyes, nose, throat, neck (week 26)	1	—
6) Lymph node palpation (week -2)	178	—
6) Lymph node palpation (week -2)	0	—
6) Lymph node palpation (week -2)	0	—
6) Lymph node palpation (week 26)	167	—
6) Lymph node palpation (week 26)	0	—
6) Lymph node palpation (week 26)	0	—
7) Musculoskeletal system (week -2)	167	—
7) Musculoskeletal system (week -2)	11	—
7) Musculoskeletal system (week -2)	0	—
7) Musculoskeletal system (week 26)	157	—
7) Musculoskeletal system (week 26)	10	—
7) Musculoskeletal system (week 26)	0	—
8) Respiratory system (week -2)	174	—
8) Respiratory system (week -2)	4	—
8) Respiratory system (week -2)	0	—
8) Respiratory system (week 26)	166	—
8) Respiratory system (week 26)	1	—
8) Respiratory system (week 26)	0	—
9) Skin (week -2)	150	—
9) Skin (week -2)	27	—
9) Skin (week -2)	1	—
9) Skin (week 26)	140	—
9) Skin (week 26)	24	—
9) Skin (week 26)	3	—
10) Thyroid gland (week -2)	176	—
10) Thyroid gland (week -2)	2	—
10) Thyroid gland (week -2)	0	—
10) Thyroid gland (week 26)	165	—
10) Thyroid gland (week 26)	2	—
10) Thyroid gland (week 26)	0	—

Secondary/registry result

Occurrence of Anti-semaglutide Binding Antibodies (Yes/no)

Time frame:Weeks 0-31

Immunogenicity (ADA)

categorical status, event

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 3 mg	2	—
Oral Semaglutide 7 mg	1	—
Oral Semaglutide 14 mg	0	—

Secondary/registry result

Occurrence of Anti-semaglutide Neutralising Antibodies (Yes/no)

Time frame:Weeks 0-31

Immunogenicity (ADA)

threshold achievement, event

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 3 mg	1	—
Oral Semaglutide 7 mg	0	—
Oral Semaglutide 14 mg	0	—

Secondary/registry result

Occurrence of Anti-semaglutide Binding Antibodies Cross Reacting With Native GLP-1 (Yes/no)

Time frame:Weeks 0-31

Immunogenicity (ADA)

categorical status, event

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 3 mg	2	—
Oral Semaglutide 7 mg	1	—
Oral Semaglutide 14 mg	0	—

Secondary/registry result

Occurrence of Anti-semaglutide Neutralising Antibodies Cross Reacting With Native GLP-1 (Yes/no)

Time frame:Weeks 0-31

Immunogenicity (ADA)

threshold achievement, event

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 3 mg	0	—
Oral Semaglutide 7 mg	0	—
Oral Semaglutide 14 mg	0	—

Secondary/registry result

Anti-semaglutide Binding Antibody Levels

Time frame:Weeks 0-31

Immunogenicity (ADA)

descriptive

Posted result

Group	Value (mean), %B/T	95% CI
Oral Semaglutide 3 mgWeek 4	15	—
Week 8	7	—
Week 31	3	—
Oral Semaglutide 7 mgWeek 4	2	—
Week 14	3	—

Secondary/registry result

Number of Treatment-emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemic Episodes During Exposure to Trial Product

Time frame:Weeks 0-31

Documented hypoglycemia

event count, event

componentsSevere hypoglycemia, Documented hypoglycemia

Posted result

Group	Value (number), Episodes	95% CI
Oral Semaglutide 3 mg	5	—
Oral Semaglutide 7 mg	2	—
Oral Semaglutide 14 mg	1	—
Placebo	1	—

Secondary/registry result

Participants With Treatment-emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemic Episodes During Exposure to Trial Product

Time frame:Weeks 0-31

Severe hypoglycemia

event count, event

componentsSevere hypoglycemia, Documented hypoglycemia

Posted result

Group	Value (number), Participants	95% CI
Oral Semaglutide 3 mg	5	—
Oral Semaglutide 7 mg	2	—
Oral Semaglutide 14 mg	1	—
Placebo	1	—

Secondary/registry result

SNAC Plasma Concentrations

Time frame:Weeks 0-26

Plasma concentration (steady state)

concentration, descriptive

Posted result

Group	Value (geometric_mean), Nanograms per milliliter (ng/mL)	95% CI
Oral Semaglutide 3 mgWeek 4: 25 minutes post-dose	443.5	—
Week 4: 40 minutes post-dose	381.7	—
Week 14: 25 minutes post-dose	384.6	—
Week 14: 40 minutes post-dose	361.0	—
Week 26: 25 minutes post-dose	412.4	—
Week 26: 40 minutes post-dose	299.1	—
Oral Semaglutide 7 mgWeek 4: 25 minutes post-dose	446.0	—
Week 4: 40 minutes post-dose	367.3	—
Week 14: 25 minutes post-dose	380.6	—
Week 14: 40 minutes post-dose	326.4	—
Week 26: 25 minutes post-dose	479.6	—
Week 26: 40 minutes post-dose	401.0	—
Oral Semaglutide 14 mgWeek 4: 25 minutes post-dose	449.4	—
Week 4: 40 minutes post-dose	387.7	—
Week 14: 25 minutes post-dose	338.2	—
Week 14: 40 minutes post-dose	262.2	—
Week 26: 25 minutes post-dose	330.9	—
Week 26: 40 minutes post-dose	300.9	—

Secondary/registry result

Semaglutide Plasma Concentrations for Population PK Analysis

Time frame:Weeks 0 - 26

Plasma concentration (steady state)

concentration, descriptive

Posted result

Group	Value (geometric_mean), Nanomoles per litre (nmol/L)	95% CI
Oral Semaglutide 3 mgWeek 4	3.120	—
Week 8	3.073	—
Week 14	2.716	—
Week 26	2.466	—
Oral Semaglutide 7 mgWeek 4	2.765	—
Week 8	6.216	—
Week 14	6.375	—
Week 26	5.016	—
Oral Semaglutide 14 mgWeek 4	2.829	—
Week 8	6.461	—
Week 14	12.69	—
Week 26	11.07	—

Secondary/protocol endpoint

Number of Treatment-emergent Adverse Events (TEAEs)

Time frame:Approximately upto week 31

Treatment-emergent AEs (any)

event count, event

Secondary/protocol endpoint

Change in Amylase - Ratio to Baseline

Time frame:Week 0, week 26

ratio, descriptive

Secondary/protocol endpoint

Change in Lipase - Ratio to Baseline

Time frame:Week 0, week 26

ratio, descriptive

Secondary/protocol endpoint

Change in Electrocardiogram (ECG) Evaluation

Time frame:Week 0, week 26

categorical status, descriptive

Secondary/protocol endpoint

Change in Physical Examination

Time frame:Week 0, week 26

descriptive

Secondary/protocol endpoint

Occurrence of Anti-semaglutide Binding Antibodies (Yes/no)

Time frame:Weeks 0-31

Immunogenicity (ADA)

categorical status, event

Secondary/protocol endpoint

Occurrence of Anti-semaglutide Neutralising Antibodies (Yes/no)

Time frame:Weeks 0-31

Immunogenicity (ADA)

categorical status, event

Secondary/protocol endpoint

Occurrence of Anti-semaglutide Binding Antibodies Cross Reacting With Native GLP-1 (Yes/no)

Time frame:Weeks 0-31

Immunogenicity (ADA)

categorical status, event

Secondary/protocol endpoint

Occurrence of Anti-semaglutide Neutralising Antibodies Cross Reacting With Native GLP-1 (Yes/no)

Time frame:Weeks 0-31

Immunogenicity (ADA)

categorical status, event

Secondary/protocol endpoint

Anti-semaglutide Binding Antibody Levels

Time frame:Weeks 0-31

Immunogenicity (ADA)

descriptive

Secondary/protocol endpoint

Number of Treatment-emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemic Episodes During Exposure to Trial Product

Time frame:Weeks 0-31

Severe hypoglycemia

event count, event

componentsSevere hypoglycemia, Documented hypoglycemia

Secondary/protocol endpoint

Participants With Treatment-emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemic Episodes During Exposure to Trial Product

Time frame:Weeks 0-31

Severe hypoglycemia

event count, event

componentsSevere hypoglycemia, Documented hypoglycemia

Secondary/protocol endpoint

SNAC Plasma Concentrations

Time frame:Weeks 0-26

Plasma concentration (steady state)

concentration, descriptive

Secondary/protocol endpoint

Semaglutide Plasma Concentrations for Population PK Analysis

Time frame:Weeks 0 - 26

Plasma concentration (steady state)

concentration, descriptive

Other clinical outcomes

2 endpoints

Secondary/registry result

Change in Eye Examination Category

Time frame:Week 0, week 26

categorical status, descriptive

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 3 mgLeft eye (week -2)	109	—
Left eye (week -2)	59	—
Left eye (week -2)	5	—
Left eye (week 26)	101	—
Left eye (week 26)	55	—
Left eye (week 26)	2	—
Right eye (week -2)	111	—
Right eye (week -2)	58	—
Right eye (week -2)	5	—
Right eye (week 26)	103	—
Right eye (week 26)	52	—
Right eye (week 26)	2	—
Oral Semaglutide 7 mgLeft eye (week -2)	112	—
Left eye (week -2)	59	—
Left eye (week -2)	4	—
Left eye (week 26)	94	—
Left eye (week 26)	55	—
Left eye (week 26)	4	—
Right eye (week -2)	116	—
Right eye (week -2)	55	—
Right eye (week -2)	4	—
Right eye (week 26)	93	—
Right eye (week 26)	56	—
Right eye (week 26)	4	—
Oral Semaglutide 14 mgLeft eye (week -2)	109	—
Left eye (week -2)	63	—
Left eye (week -2)	3	—
Left eye (week 26)	99	—
Left eye (week 26)	54	—
Left eye (week 26)	3	—
Right eye (week -2)	108	—
Right eye (week -2)	63	—
Right eye (week -2)	4	—
Right eye (week 26)	98	—
Right eye (week 26)	55	—
Right eye (week 26)	3	—
PlaceboLeft eye (week -2)	122	—
Left eye (week -2)	54	—
Left eye (week -2)	2	—
Left eye (week 26)	105	—
Left eye (week 26)	54	—
Left eye (week 26)	3	—
Right eye (week -2)	120	—
Right eye (week -2)	55	—
Right eye (week -2)	3	—
Right eye (week 26)	106	—
Right eye (week 26)	53	—
Right eye (week 26)	3	—

Secondary/protocol endpoint

Change in Eye Examination Category

Time frame:Week 0, week 26

categorical status, improvement

Other (unclassified)

1 endpoint

Secondary/protocol endpoint/low confidence

Change in Fasting Glucagon - Ratio to Baseline

Time frame:Week 0, week 26

ratio, improvement

Publications (10)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Fast tipping point sensitivity analyses in clinical trials with missing continuous outcomes under multiple imputation.
Journal of biopharmaceutical statistics2022 Nov 2PMID35653556doi:10.1080/10543406.2022.2058525via CT.gov reference
Impact of semaglutide on high-sensitivity C-reactive protein: exploratory patient-level analyses of SUSTAIN and PIONEER randomized clinical trials.
Cardiovascular diabetology2022 Sep 2PMID36056351doi:10.1186/s12933-022-01585-7via clinicaltrials gov reference derived + pubmed nct search
Efficacy and safety of oral semaglutide by subgroups of patient characteristics in the PIONEER phase 3 programme.
Diabetes, obesity & metabolism2022 Jul (month)PMID35373893doi:10.1111/dom.14710via CT.gov reference
Efficacy and safety of oral semaglutide in Japanese patients with type 2 diabetes: A post hoc subgroup analysis of the PIONEER 1, 3, 4 and 8 trials.
Diabetes, obesity & metabolism2021 Dec (month)PMID34472698doi:10.1111/dom.14536via CT.gov reference
Effects of semaglutide on risk of cardiovascular events across a continuum of cardiovascular risk: combined post hoc analysis of the SUSTAIN and PIONEER trials.
Cardiovascular diabetology2020 Sep 30PMID32998732doi:10.1186/s12933-020-01106-4via clinicaltrials gov reference derived + pubmed nct search
Efficacy, safety and cardiovascular outcomes of once-daily oral semaglutide in patients with type 2 diabetes: The PIONEER programme.
Diabetes, obesity & metabolism2020 Aug (month)PMID32267058doi:10.1111/dom.14054via clinicaltrials gov reference derived + pubmed nct search
Semaglutide (SUSTAIN and PIONEER) reduces cardiovascular events in type 2 diabetes across varying cardiovascular risk.
Diabetes, obesity & metabolism2020 Mar (month)PMID31903692doi:10.1111/dom.13955via clinicaltrials gov reference derived + pubmed nct search
Incorporating and interpreting regulatory guidance on estimands in diabetes clinical trials: The PIONEER 1 randomized clinical trial as an example.
Diabetes, obesity & metabolism2019 Oct (month)PMID31168921doi:10.1111/dom.13804via CT.gov background
PIONEER 1: Randomized Clinical Trial of the Efficacy and Safety of Oral Semaglutide Monotherapy in Comparison With Placebo in Patients With Type 2 Diabetes.
Diabetes care2019 Sep (month)PMID31186300doi:10.2337/dc19-0749via CT.gov reference + pubmed nct search
Validation of a new measure of quality of life in obesity trials: Impact of Weight on Quality of Life-Lite Clinical Trials Version.
Clinical obesity2019 Jun (month)PMID30993900doi:10.1111/cob.12310via CT.gov background + pubmed nct search

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 1, 2026

Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.