PIONEER 8

CompletedPhase 3Results posted

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

Efficacy and Safety of Oral Semaglutide Versus Placebo in Subjects With Type 2 Diabetes Mellitus Treated With Insulin. A 52-week, Randomised, Double-blind, Placebo-controlled Trial (PIONEER 8 - Insulin add-on)

Lead sponsor

Novo Nordisk A/S

Asset

Semaglutide

Oral · GLP-1 agonist

Listed sites

118

Recruiting sites

—

Enrollment

731

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 IDNCT03021187

Org study IDNN9924-4280

Secondary ID2016-000988-16

Secondary IDJapicCTI-173508JAPIC

Secondary IDU1111-1180-3637World Health Organization (WHO)

Timeline

Milestones

Study first posted2017-01-13estimated

Study start2017-02-02actual

Primary completion2018-01-18actual

Study completion2018-08-22actual

Results first posted2019-11-07actual

Last update posted2020-03-02actual

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. - Diagnosed with type 2 diabetes mellitus 90 days or more prior to the day of screening. - HbA1c (glycosylated haemoglobin) of 7.0-9.5% (53-80 mmol/mol) (both inclusive). - Stable treatment with one of the following insulin regimens (minimum 10 IU/day) 90 or more days prior to the day of screening. Maximum 20% change in total daily dose is acceptable: (1) Basal insulin alone or (2) Basal and bolus insulin in any combination or (3) Premixed insulin including combinations of soluble insulins 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 Greece only: adequate contraceptive measures are defined as combined hormonal contraception (containing oestrogen and progesterone), which suppress ovulation (oral, intravaginal, percutaneous), progesterone-only hormonal contraception which suppress ovulation (oral, injectable, implantable), intrauterine device, hormone-releasing intrauterine system, bilateral tubal occlusion, partner with vasectomy, sexual abstinence. For Japan only: Adequate contraceptive measures are abstinence (not having sex), diaphragm, condom (by the partner), intrauterine device, sponge, spermicide or oral contraceptives. For Canada only: adequate contraceptive measures are defined as combined hormonal contraception (containing oestrogen and progesterone), which suppress ovulation (oral, intravaginal, percutaneous), progesterone-only hormonal contraception which suppress ovulation (oral, injectable, implantable), intrauterine device, hormone-releasing intrauterine system, bilateral tubal occlusion, partner with vasectomy, sexual abstinence - 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 and randomisation. - 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) less than 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 change of insulin treatment for acute illness for a total of 14 days or less. - Known hypoglycaemic unawareness according to Clarke's questionnaire. - 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). - Subjects with alanine aminotransferase (ALT) more than 2.5 x upper normal limit (UNL).

Endpoints (74)

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

Weight & body composition

Cardiometabolic biomarkers

Patient-reported / QoL

Other clinical outcomes

Weight & body composition

14 endpoints

Secondary/registry result

Change in Body Weight (Week 26)

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	-1.4	—
On-treatment without rescue medication	-1.5	—
Oral Semaglutide 7 mgIn trial	-2.6	—
On-treatment without rescue medication	-3.0	—
Oral Semaglutide 14 mgIn trial	-3.7	—
On-treatment without rescue medication	-3.9	—
PlaceboIn trial	-0.5	—
On-treatment without rescue medication	-0.5	—

Mean treatment difference-0.995% CI-1.8 – -0.0p0.0392Pattern mixture model

Mean treatment difference-2.095% CI-3.0 – -1.0p0.0001Pattern mixture model

Mean treatment difference-3.395% CI-4.2 – -2.3p<0.0001Pattern mixture model

Mean treatment difference-0.995% CI-1.6 – -0.2p0.0111MMRM

Mean treatment difference-2.595% CI-3.2 – -1.8p<0.0001MMRM

Mean treatment difference-3.795% CI-4.4 – -3.0p<0.0001MMRM

Secondary/registry result

Change in Body Weight (kg) (Week 52)

Time frame:Week 0, week 52

Body weight, absolute change (kg)

change from baseline, improvement

Posted result

Group	Value (mean), Kg	95% CI
Oral Semaglutide 3 mg	-0.9	—
Oral Semaglutide 7 mg	-2.2	—
Oral Semaglutide 14 mg	-3.8	—
Placebo	0.5	—

Secondary/registry result

Change in Body Weight (Percentage)

Time frame:Week 0, week 26, week 52

Body weight, % change

percent change from baseline, improvement

Posted result

Group	Value (mean), Percentage change	95% CI
Oral Semaglutide 3 mgWeek 26	-1.73	—
Week 52	-1.18	—
Oral Semaglutide 7 mgWeek 26	-3.11	—
Week 52	-2.54	—
Oral Semaglutide 14 mgWeek 26	-4.30	—
Week 52	-4.42	—
PlaceboWeek 26	-0.47	—
Week 52	0.65	—

Secondary/registry result

Change in Body Mass Index

Time frame:Week 0, week 26, week 52

BMI, change

change from baseline, improvement

Posted result

Group	Value (mean), kg/m^2	95% CI
Oral Semaglutide 3 mgWeek 26	-0.5	—
Week 52	-0.3	—
Oral Semaglutide 7 mgWeek 26	-1.0	—
Week 52	-0.8	—
Oral Semaglutide 14 mgWeek 26	-1.4	—
Week 52	-1.4	—
PlaceboWeek 26	-0.2	—
Week 52	0.2	—

Secondary/registry result

Change in Waist Circumference

Time frame:Week 0, week 26, week 52

Waist circumference, change

change from baseline, improvement

Posted result

Group	Value (mean), cm	95% CI
Oral Semaglutide 3 mgWeek 26	-0.9	—
Week 52	-0.8	—
Oral Semaglutide 7 mgWeek 26	-2.3	—
Week 52	-2.3	—
Oral Semaglutide 14 mgWeek 26	-3.6	—
Week 52	-4.0	—
PlaceboWeek 26	-0.6	—
Week 52	0.3	—

Secondary/registry result

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

Time frame:Week 26, week 52

≥5% weight-loss responders

threshold achievement, improvement

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 3 mgWeek 26	23	—
Week 26	154	—
Week 52	30	—
Week 52	144	—
Oral Semaglutide 7 mgWeek 26	53	—
Week 26	121	—
Week 52	48	—
Week 52	123	—
Oral Semaglutide 14 mgWeek 26	67	—
Week 26	106	—
Week 52	67	—
Week 52	103	—
PlaceboWeek 26	5	—
Week 26	172	—
Week 52	9	—
Week 52	164	—

Secondary/registry result

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

Time frame:Week 26, week 52

≥10% weight-loss responders

threshold achievement, improvement

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 3 mgWeek 26	2	—
Week 26	175	—
Week 52	4	—
Week 52	170	—
Oral Semaglutide 7 mgWeek 26	12	—
Week 26	162	—
Week 52	17	—
Week 52	154	—
Oral Semaglutide 14 mgWeek 26	19	—
Week 26	154	—
Week 52	21	—
Week 52	149	—
PlaceboWeek 26	1	—
Week 26	176	—
Week 52	1	—
Week 52	172	—

Secondary/protocol endpoint

Change in Body Weight (Week 26)

Time frame:Week 0, week 26

Body weight, absolute change (kg)

change from baseline, improvement

Secondary/protocol endpoint

Change in Body Weight (kg) (Week 52)

Time frame:Week 0, week 52

Body weight, absolute change (kg)

change from baseline, improvement

Secondary/protocol endpoint

Change in Body Weight (Percentage)

Time frame:Week 0, week 26, week 52

Body weight, % change

percent change from baseline, improvement

Secondary/protocol endpoint

Change in Body Mass Index

Time frame:Week 0, week 26, week 52

BMI, change

change from baseline, improvement

Secondary/protocol endpoint

Change in Waist Circumference

Time frame:Week 0, week 26, week 52

Waist circumference, change

change from baseline, improvement

Secondary/protocol endpoint

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

Time frame:Week 26, week 52

≥5% weight-loss responders

threshold achievement, improvement

Secondary/protocol endpoint

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

Time frame:Week 26, week 52

≥10% weight-loss responders

threshold achievement, improvement

Glycemic / diabetes

24 endpoints

Primary/registry result

Change in HbA1c (Week 26)

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	-0.5	—
On-treatment without rescue medication	-0.6	—
Oral Semaglutide 7 mgIn-trial	-1.0	—
On-treatment without rescue medication	-1.1	—
Oral Semaglutide 14 mgIn-trial	-1.3	—
On-treatment without rescue medication	-1.4	—
PlaceboIn-trial	-0.1	—
On-treatment without rescue medication	-0.1	—

Mean treatment difference-0.595% CI-0.7 – -0.3p< 0.0001Pattern mixture model

Mean treatment difference-0.995% CI-1.1 – -0.7p< 0.0001Pattern mixture model

Mean treatment difference-1.295% CI-1.4 – -1.0p< 0.0001Pattern mixture model

Mean treatment difference-0.695% CI-0.7 – -0.4p<0.0001MMRM

Mean treatment difference-1.095% CI-1.2 – -0.8p<0.0001MMRM

Mean treatment difference-1.495% CI-1.6 – -1.2p<0.0001MMRM

Primary/protocol endpoint

Change in HbA1c (Week 26)

Time frame:Week 0, week 26

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Secondary/registry result

Change in HbA1c (Week 52)

Time frame:Week 0, week 52

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Posted result

Group	Value (mean), Percentage of HbA1c	95% CI
Oral Semaglutide 3 mg	-0.6	—
Oral Semaglutide 7 mg	-0.9	—
Oral Semaglutide 14 mg	-1.2	—
Placebo	-0.2	—

Secondary/registry result

Change in Fasting Plasma Glucose (FPG)

Time frame:Week 0, week 26, week 52

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Posted result

Group	Value (mean), mmol/L	95% CI
Oral Semaglutide 3 mgWeek 26	-0.45	—
Week 52	-0.81	—
Oral Semaglutide 7 mgWeek 26	-1.14	—
Week 52	-1.12	—
Oral Semaglutide 14 mgWeek 26	-1.36	—
Week 52	-1.60	—
PlaceboWeek 26	0.51	—
Week 52	-0.09	—

Secondary/registry result

Change in Self-measured Plasma Glucose (SMPG) Mean 7-point Profile

Time frame:Week 0, week 26, week 52

Postprandial glucose

change from baseline, improvement

Posted result

Group	Value (mean), mmol/L	95% CI
Oral Semaglutide 3 mgWeek 26	-1.2	—
Week 52	-1.6	—
Oral Semaglutide 7 mgWeek 26	-1.8	—
Week 52	-1.7	—
Oral Semaglutide 14 mgWeek 26	-2.0	—
Week 52	-2.0	—
PlaceboWeek 26	-0.3	—
Week 52	-0.9	—

Secondary/registry result

Change in SMPG Mean Postprandial Increment Over All Meals

Time frame:Week 0, week 26, week 52

Postprandial glucose

change from baseline, improvement

Posted result

Group	Value (mean), mmol/L	95% CI
Oral Semaglutide 3 mgWeek 26	-0.3	—
Week 52	-0.3	—
Oral Semaglutide 7 mgWeek 26	-0.8	—
Week 52	-0.7	—
Oral Semaglutide 14 mgWeek 26	-1.2	—
Week 52	-0.7	—
PlaceboWeek 26	-0.1	—
Week 52	-0.3	—

Secondary/registry result

Change in Total Daily Insulin Dose

Time frame:Week 0, week 26, week 52

change from baseline, improvement

Posted result

Group	Value (mean), Units/day	95% CI
Oral Semaglutide 3 mgWeek 26	-5	—
Week 52	1	—
Oral Semaglutide 7 mgWeek 26	-9	—
Week 52	-8	—
Oral Semaglutide 14 mgWeek 26	-8	—
Week 52	-5	—
PlaceboWeek 26	-2	—
Week 52	8	—

Secondary/registry result

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

Time frame:Week 26, week 52

HbA1c <7.0% achievement

threshold achievement, improvement

LOINC 4548-4

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 3 mgWeek 26	50	—
Week 26	126	—
Week 52	50	—
Week 52	123	—
Oral Semaglutide 7 mgWeek 26	74	—
Week 26	100	—
Week 52	67	—
Week 52	102	—
Oral Semaglutide 14 mgWeek 26	101	—
Week 26	72	—
Week 52	91	—
Week 52	77	—
PlaceboWeek 26	12	—
Week 26	164	—
Week 52	16	—
Week 52	156	—

Secondary/registry result

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

Time frame:Week 26, week 52

HbA1c <6.5% achievement

threshold achievement, improvement

LOINC 4548-4

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 3 mgWeek 26	24	—
Week 26	152	—
Week 52	20	—
Week 52	153	—
Oral Semaglutide 7 mgWeek 26	45	—
Week 26	129	—
Week 52	33	—
Week 52	136	—
Oral Semaglutide 14 mgWeek 26	74	—
Week 26	99	—
Week 52	65	—
Week 52	103	—
PlaceboWeek 26	6	—
Week 26	170	—
Week 52	4	—
Week 52	168	—

Secondary/registry result

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

Time frame:Week 26, week 52

HbA1c <7.0% achievement

threshold achievement, improvement

LOINC 4548-4

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 3 mgWeek 26	32	—
Week 26	144	—
Week 52	27	—
Week 52	146	—
Oral Semaglutide 7 mgWeek 26	47	—
Week 26	127	—
Week 52	43	—
Week 52	126	—
Oral Semaglutide 14 mgWeek 26	76	—
Week 26	97	—
Week 52	61	—
Week 52	107	—
PlaceboWeek 26	4	—
Week 26	172	—
Week 52	8	—
Week 52	164	—

Secondary/registry result

Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no)

Time frame:Week 26, week 52

threshold achievement, improvement

componentsHbA1c, change, Body weight, % change

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 3 mgWeek 26	28	—
Week 26	148	—
Week 52	20	—
Week 52	153	—
Oral Semaglutide 7 mgWeek 26	51	—
Week 26	123	—
Week 52	37	—
Week 52	132	—
Oral Semaglutide 14 mgWeek 26	76	—
Week 26	97	—
Week 52	64	—
Week 52	104	—
PlaceboWeek 26	7	—
Week 26	169	—
Week 52	5	—
Week 52	167	—

Secondary/registry result

Time to Additional Anti-diabetic Medication

Time frame:Weeks 0-52

threshold achievement, event

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 3 mgWeek 0-26	9	—
Week 0-52	61	—
Oral Semaglutide 7 mgWeek 0-26	8	—
Week 0-52	45	—
Oral Semaglutide 14 mgWeek 0-26	8	—
Week 0-52	44	—
PlaceboWeek 0-26	11	—
Week 0-52	75	—

Hazard Ratio (HR)0.7395% CI0.53 – 1.02p0.0627Regression, Cox

Hazard Ratio (HR)0.6395% CI0.44 – 0.89p0.0083Regression, Cox

Hazard Ratio (HR)0.5795% CI0.40 – 0.81p0.0019Regression, Cox

Secondary/registry result

Time to Rescue Medication

Time frame:Weeks 0-52

threshold achievement, event

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 3 mgWeek 0-26	5	—
Week 0-52	54	—
Oral Semaglutide 7 mgWeek 0-26	2	—
Week 0-52	33	—
Oral Semaglutide 14 mgWeek 0-26	4	—
Week 0-52	31	—
PlaceboWeek 0-26	9	—
Week 0-52	67	—

Hazard Ratio (HR)0.7595% CI0.53 – 1.08p0.1210Regression, Cox

Hazard Ratio (HR)0.4895% CI0.32 – 0.74p0.0007Regression, Cox

Hazard Ratio (HR)0.4895% CI0.31 – 0.73p0.0006Regression, Cox

Secondary/protocol endpoint

Change in HbA1c (Week 52)

Time frame:Week 0, week 52

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Secondary/protocol endpoint

Change in Fasting Plasma Glucose (FPG)

Time frame:Week 0, week 26, week 52

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Secondary/protocol endpoint

Change in Self-measured Plasma Glucose (SMPG) Mean 7-point Profile

Time frame:Week 0, week 26, week 52

Postprandial glucose

change from baseline, improvement

Secondary/protocol endpoint

Change in SMPG Mean Postprandial Increment Over All Meals

Time frame:Week 0, week 26, week 52

Postprandial glucose

change from baseline, improvement

Secondary/protocol endpoint

Change in Total Daily Insulin Dose

Time frame:Week 0, week 26, week 52

change from baseline, improvement

Secondary/protocol endpoint

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

Time frame:Week 26, week 52

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, week 52

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 no Weight Gain (Yes/no)

Time frame:Week 26, week 52

HbA1c <7.0% achievement

threshold achievement, improvement

LOINC 4548-4

Secondary/protocol endpoint

Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no)

Time frame:Week 26, week 52

threshold achievement, improvement

componentsHbA1c, change, Body weight, % change

Secondary/protocol endpoint

Time to Additional Anti-diabetic Medication

Time frame:Weeks 0-52

event count, event

Secondary/protocol endpoint

Time to Rescue Medication

Time frame:Weeks 0-52

event count, event

Cardiometabolic biomarkers

12 endpoints

Secondary/registry result

Change in Total Cholesterol - Ratio to Baseline

Time frame:Week 0, week 26, week 52

Total cholesterol, change

ratio, improvement

LOINC 2093-3

Posted result

Group	Value (geometric_mean), Ratio of total cholesterol	95% CI
Oral Semaglutide 3 mgWeek 26	0.99	—
Week 52	0.98	—
Oral Semaglutide 7 mgWeek 26	0.95	—
Week 52	0.97	—
Oral Semaglutide 14 mgWeek 26	0.95	—
Week 52	0.95	—
PlaceboWeek 26	1.03	—
Week 52	1.00	—

Secondary/registry result

Change in LDL Cholesterol - Ratio to Baseline

Time frame:Week 0, week 26, week 52

LDL-C, change

ratio, improvement

LOINC 13457-7

Posted result

Group	Value (geometric_mean), Ratio of LDL cholesterol	95% CI
Oral Semaglutide 3 mgWeek 26	0.98	—
Week 52	0.97	—
Oral Semaglutide 7 mgWeek 26	0.93	—
Week 52	0.96	—
Oral Semaglutide 14 mgWeek 26	0.93	—
Week 52	0.95	—
PlaceboWeek 26	1.03	—
Week 52	1.00	—

Secondary/registry result

Change in HDL Cholesterol - Ratio to Baseline

Time frame:Week 0, week 26, week 52

HDL-C, change

ratio, improvement

LOINC 2085-9

Posted result

Group	Value (geometric_mean), Ratio of HDL cholesterol	95% CI
Oral Semaglutide 3 mgWeek 26	1.00	—
Week 52	1.01	—
Oral Semaglutide 7 mgWeek 26	0.98	—
Week 52	0.98	—
Oral Semaglutide 14 mgWeek 26	0.98	—
Week 52	1.01	—
PlaceboWeek 26	1.01	—
Week 52	1.00	—

Secondary/registry result

Change in Triglycerides - Ratio to Baseline

Time frame:Week 0, week 26, week 52

Triglycerides, change

ratio, improvement

LOINC 2571-8

Posted result

Group	Value (geometric_mean), Ratio of triglycerides	95% CI
Oral Semaglutide 3 mgWeek 26	0.97	—
Week 52	0.93	—
Oral Semaglutide 7 mgWeek 26	0.92	—
Week 52	0.94	—
Oral Semaglutide 14 mgWeek 26	0.91	—
Week 52	0.86	—
PlaceboWeek 26	0.99	—
Week 52	0.97	—

Secondary/registry result

Change in Pulse Rate

Time frame:Week 0, week 26, week 52

Heart rate, change

change from baseline, improvement

Posted result

Group	Value (mean), Beats/minute	95% CI
Oral Semaglutide 3 mgWeek 26	1	—
Week 52	-0	—
Oral Semaglutide 7 mgWeek 26	2	—
Week 52	1	—
Oral Semaglutide 14 mgWeek 26	3	—
Week 52	2	—
PlaceboWeek 26	-0	—
Week 52	0	—

Secondary/registry result

Change in SBP and DBP

Time frame:Week 0, week 26, week 52

change from baseline, improvement

componentsSystolic BP, change, Diastolic BP, change

Posted result

Group	Value (mean), mmHg	95% CI
Oral Semaglutide 3 mgSBP: Week 26	-1	—
SBP: Week 52	-1	—
DBP: Week 26	-0	—
DBP: Week 52	-1	—
Oral Semaglutide 7 mgSBP: Week 26	-3	—
SBP: Week 52	-3	—
DBP: Week 26	-1	—
DBP: Week 52	-2	—
Oral Semaglutide 14 mgSBP: Week 26	-5	—
SBP: Week 52	-6	—
DBP: Week 26	-1	—
DBP: Week 52	-2	—
PlaceboSBP: Week 26	1	—
SBP: Week 52	0	—
DBP: Week 26	0	—
DBP: Week 52	-0	—

Secondary/protocol endpoint

Change in Total Cholesterol - Ratio to Baseline

Time frame:Week 0, week 26, week 52

Total cholesterol, change

ratio, improvement

LOINC 2093-3

Secondary/protocol endpoint

Change in LDL Cholesterol - Ratio to Baseline

Time frame:Week 0, week 26, week 52

LDL-C, change

ratio, improvement

LOINC 13457-7

Secondary/protocol endpoint

Change in HDL Cholesterol - Ratio to Baseline

Time frame:Week 0, week 26, week 52

HDL-C, change

ratio, improvement

LOINC 2085-9

Secondary/protocol endpoint

Change in Triglycerides - Ratio to Baseline

Time frame:Week 0, week 26, week 52

Triglycerides, change

ratio, improvement

Secondary/protocol endpoint

Change in Pulse Rate

Time frame:Week 0, week 26, week 52

Heart rate, change

change from baseline, improvement

Secondary/protocol endpoint

Change in SBP and DBP

Time frame:Week 0, week 26, week 52

change from baseline, improvement

componentsSystolic BP, change, Diastolic BP, change

Patient-reported / QoL

6 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, week 52

SF-36 total

change from baseline, improvement

Posted result

Group	Value (mean), Score on a scale	95% CI
Oral Semaglutide 3 mg1) Physical functioning (Week 26)	0.53	—
1) Physical functioning (Week 52)	0.51	—
2) Role Physical (Week 26)	-0.32	—
2) Role Physical (Week 52)	0.00	—
3) Bodily Pain (Week 26)	-0.02	—
3) Bodily Pain (Week 52)	-0.40	—
4) General Health (Week 26)	1.43	—
4) General Health (Week 52)	0.92	—
5) Vitality (Week 26)	-0.56	—
5) Vitality (Week 52)	-0.53	—
6) Social functioning (Week 26)	-0.31	—
6) Social functioning (Week 52)	0.11	—
7) Role emotional (Week 26)	-0.94	—
7) Role emotional (Week 52)	0.77	—
8) Mental health (Week 26)	-1.41	—
8) Mental health (Week 52)	-0.48	—
9) Physical component summary (Week 26)	0.94	—
9) Physical component summary (Week 52)	0.26	—
10) Mental component summary (Week 26)	-1.41	—
10) Mental component summary (Week 52)	-0.09	—
Oral Semaglutide 7 mg1) Physical functioning (Week 26)	0.52	—
1) Physical functioning (Week 52)	-0.40	—
2) Role Physical (Week 26)	-0.43	—
2) Role Physical (Week 52)	-0.76	—
3) Bodily Pain (Week 26)	1.47	—
3) Bodily Pain (Week 52)	0.56	—
4) General Health (Week 26)	0.70	—
4) General Health (Week 52)	0.75	—
5) Vitality (Week 26)	-1.27	—
5) Vitality (Week 52)	-1.43	—
6) Social functioning (Week 26)	0.34	—
6) Social functioning (Week 52)	-0.61	—
7) Role emotional (Week 26)	0.62	—
7) Role emotional (Week 52)	-0.34	—
8) Mental health (Week 26)	-0.82	—
8) Mental health (Week 52)	-0.74	—
9) Physical component summary (Week 26)	0.75	—
9) Physical component summary (Week 52)	0.12	—
10) Mental component summary (Week 26)	-0.55	—
10) Mental component summary (Week 52)	-0.89	—
Oral Semaglutide 14 mg1) Physical functioning (Week 26)	-0.07	—
1) Physical functioning (Week 52)	-0.32	—
2) Role Physical (Week 26)	0.04	—
2) Role Physical (Week 52)	-0.87	—
3) Bodily Pain (Week 26)	-0.18	—
3) Bodily Pain (Week 52)	-0.21	—
4) General Health (Week 26)	1.26	—
4) General Health (Week 52)	1.38	—
5) Vitality (Week 26)	0.14	—
5) Vitality (Week 52)	0.70	—
6) Social functioning (Week 26)	-0.51	—
6) Social functioning (Week 52)	0.03	—
7) Role emotional (Week 26)	0.24	—
7) Role emotional (Week 52)	0.09	—
8) Mental health (Week 26)	0.99	—
8) Mental health (Week 52)	0.89	—
9) Physical component summary (Week 26)	-0.02	—
9) Physical component summary (Week 52)	-0.36	—
10) Mental component summary (Week 26)	0.49	—
10) Mental component summary (Week 52)	0.82	—
Placebo1) Physical functioning (Week 26)	-0.82	—
1) Physical functioning (Week 52)	-0.77	—
2) Role Physical (Week 26)	-0.39	—
2) Role Physical (Week 52)	-0.93	—
3) Bodily Pain (Week 26)	-0.72	—
3) Bodily Pain (Week 52)	-0.64	—
4) General Health (Week 26)	-0.36	—
4) General Health (Week 52)	-1.43	—
5) Vitality (Week 26)	-1.69	—
5) Vitality (Week 52)	-1.09	—
6) Social functioning (Week 26)	-1.10	—
6) Social functioning (Week 52)	-1.74	—
7) Role emotional (Week 26)	-1.50	—
7) Role emotional (Week 52)	-2.78	—
8) Mental health (Week 26)	-2.32	—
8) Mental health (Week 52)	-1.30	—
9) Physical component summary (Week 26)	-0.05	—
9) Physical component summary (Week 52)	-0.41	—
10) Mental component summary (Week 26)	-2.16	—
10) Mental component summary (Week 52)	-2.19	—

Secondary/registry result

Change in IWQoL-Lite-CT: Total Score and Scores From the 4 Domains

Time frame:Week 0, week 26, week 52

IWQOL-Lite total

change from baseline, improvement

Posted result

Group	Value (mean), Score on a scale	95% CI
Oral Semaglutide 3 mg1) Psychosocial (Week 26)	1.45	—
1) Psychosocial (Week 52)	1.96	—
2) Physical (Week 26)	2.29	—
2) Physical (Week 52)	3.10	—
3) Physical function(Week 26)	1.88	—
3) Physical function(Week 52)	3.45	—
4) Pain/discomfort (Week 26)	3.30	—
4) Pain/discomfort (Week 52)	2.23	—
5) IWQOL-Lite-CT Total (Week 26)	1.74	—
5) IWQOL-Lite-CT Total (Week 52)	2.35	—
Oral Semaglutide 7 mg1) Psychosocial (Week 26)	-0.32	—
1) Psychosocial (Week 52)	-0.92	—
2) Physical (Week 26)	-0.66	—
2) Physical (Week 52)	-0.53	—
3) Physical function(Week 26)	-0.35	—
3) Physical function(Week 52)	-0.59	—
4) Pain/discomfort (Week 26)	-1.45	—
4) Pain/discomfort (Week 52)	-0.37	—
5) IWQOL-Lite-CT Total (Week 26)	-0.45	—
5) IWQOL-Lite-CT Total (Week 52)	-0.79	—
Oral Semaglutide 14 mg1) Psychosocial (Week 26)	4.10	—
1) Psychosocial (Week 52)	5.35	—
2) Physical (Week 26)	2.15	—
2) Physical (Week 52)	2.50	—
3) Physical function(Week 26)	2.51	—
3) Physical function(Week 52)	2.59	—
4) Pain/discomfort (Week 26)	1.23	—
4) Pain/discomfort (Week 52)	2.28	—
5) IWQOL-Lite-CT Total (Week 26)	3.41	—
5) IWQOL-Lite-CT Total (Week 52)	4.35	—
Placebo1) Psychosocial (Week 26)	-0.49	—
1) Psychosocial (Week 52)	-0.46	—
2) Physical (Week 26)	-1.75	—
2) Physical (Week 52)	-1.24	—
3) Physical function(Week 26)	-1.70	—
3) Physical function(Week 52)	-0.98	—
4) Pain/discomfort (Week 26)	-1.85	—
4) Pain/discomfort (Week 52)	-1.88	—
5) IWQOL-Lite-CT Total (Week 26)	-0.94	—
5) IWQOL-Lite-CT Total (Week 52)	-0.73	—

Secondary/registry result

Change in DTSQs: Individual Items and Treatment Satisfaction Score (6 of the 8 Items Summed)

Time frame:Week 0, week 26, week 52

change from baseline, improvement

Posted result

Group	Value (mean), Score on a scale	95% CI
Oral Semaglutide 3 mgSatisfaction with treatment: wk 26	0.47	—
Satisfaction with treatment: wk 52	0.53	—
Feeling of unacceptably high blood sugars: wk 26	-0.62	—
Feeling of unacceptably high blood sugars: wk 52	-0.70	—
Feeling of unacceptably low blood sugars: wk 26	0.07	—
Feeling of unacceptably low blood sugars: wk 52	0.04	—
Convenience of treatment: wk 26	0.51	—
Convenience of treatment: wk 52	0.38	—
Flexibility of treatment: wk 26	0.31	—
Flexibility of treatment: wk 52	0.25	—
Satisfaction with understading of diabetes: wk 26	0.24	—
Satisfaction with understading of diabetes: wk 52	0.25	—
Recommending treatment to others: wk 26	0.20	—
Recommending treatment to others: wk 52	0.32	—
Satisfaction to continue present treatment: wk 26	0.40	—
Satisfaction to continue present treatment: wk 52	0.41	—
Total treatment satisfaction: wk 26	2.12	—
Total treatmemt satisfaction: wk 52	2.14	—
Oral Semaglutide 7 mgSatisfaction with treatment: wk 26	0.59	—
Satisfaction with treatment: wk 52	0.51	—
Feeling of unacceptably high blood sugars: wk 26	-1.23	—
Feeling of unacceptably high blood sugars: wk 52	-1.15	—
Feeling of unacceptably low blood sugars: wk 26	-0.06	—
Feeling of unacceptably low blood sugars: wk 52	-0.10	—
Convenience of treatment: wk 26	0.50	—
Convenience of treatment: wk 52	0.52	—
Flexibility of treatment: wk 26	0.37	—
Flexibility of treatment: wk 52	0.42	—
Satisfaction with understading of diabetes: wk 26	0.31	—
Satisfaction with understading of diabetes: wk 52	0.35	—
Recommending treatment to others: wk 26	0.66	—
Recommending treatment to others: wk 52	0.63	—
Satisfaction to continue present treatment: wk 26	0.57	—
Satisfaction to continue present treatment: wk 52	0.56	—
Total treatment satisfaction: wk 26	3.00	—
Total treatmemt satisfaction: wk 52	2.99	—
Oral Semaglutide 14 mgSatisfaction with treatment: wk 26	0.63	—
Satisfaction with treatment: wk 52	0.78	—
Feeling of unacceptably high blood sugars: wk 26	-1.29	—
Feeling of unacceptably high blood sugars: wk 52	-1.34	—
Feeling of unacceptably low blood sugars: wk 26	0.13	—
Feeling of unacceptably low blood sugars: wk 52	-0.06	—
Convenience of treatment: wk 26	0.50	—
Convenience of treatment: wk 52	0.44	—
Flexibility of treatment: wk 26	0.40	—
Flexibility of treatment: wk 52	0.46	—
Satisfaction with understading of diabetes: wk 26	0.27	—
Satisfaction with understading of diabetes: wk 52	0.34	—
Recommending treatment to others: wk 26	0.53	—
Recommending treatment to others: wk 52	0.65	—
Satisfaction to continue present treatment: wk 26	0.58	—
Satisfaction to continue present treatment: wk 52	0.65	—
Total treatment satisfaction: wk 26	2.90	—
Total treatmemt satisfaction: wk 52	3.32	—
PlaceboSatisfaction with treatment: wk 26	0.18	—
Satisfaction with treatment: wk 52	0.20	—
Feeling of unacceptably high blood sugars: wk 26	-0.28	—
Feeling of unacceptably high blood sugars: wk 52	-0.41	—
Feeling of unacceptably low blood sugars: wk 26	-0.15	—
Feeling of unacceptably low blood sugars: wk 52	-0.02	—
Convenience of treatment: wk 26	0.20	—
Convenience of treatment: wk 52	0.19	—
Flexibility of treatment: wk 26	0.23	—
Flexibility of treatment: wk 52	0.23	—
Satisfaction with understading of diabetes: wk 26	0.04	—
Satisfaction with understading of diabetes: wk 52	0.03	—
Recommending treatment to others: wk 26	0.02	—
Recommending treatment to others: wk 52	-0.01	—
Satisfaction to continue present treatment: wk 26	0.09	—
Satisfaction to continue present treatment: wk 52	0.03	—
Total treatment satisfaction: wk 26	0.76	—
Total treatmemt satisfaction: wk 52	0.67	—

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, week 52

SF-36 total

change from baseline, improvement

Secondary/protocol endpoint

Change in IWQoL-Lite-CT: Total Score and Scores From the 4 Domains

Time frame:Week 0, week 26, week 52

IWQOL-Lite total

change from baseline, improvement

Secondary/protocol endpoint

Change in DTSQs: Individual Items and Treatment Satisfaction Score (6 of the 8 Items Summed)

Time frame:Week 0, week 26, week 52

change from baseline, improvement

Safety / tolerability / PK

16 endpoints

Secondary/registry result

Number of Treatment-emergent Adverse Events (TEAEs) During Exposure to Trial Product

Time frame:Weeks 0-57

Treatment-emergent AEs (any)

event count, event

Posted result

Group	Value (number), Events	95% CI
Oral Semaglutide 3 mg	626	—
Oral Semaglutide 7 mg	555	—
Oral Semaglutide 14 mg	586	—
Placebo	464	—

Secondary/registry result

Number of Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes

Time frame:Weeks 0-57

Documented hypoglycemia

event count, event

componentsSevere hypoglycemia, Documented hypoglycemia

Posted result

Group	Value (number), Episodes	95% CI
Oral Semaglutide 3 mg	196	—
Oral Semaglutide 7 mg	180	—
Oral Semaglutide 14 mg	147	—
Placebo	156	—

Secondary/registry result

Participants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes

Time frame:Weeks 0-57

Documented hypoglycemia

threshold achievement, event

componentsSevere hypoglycemia, Documented hypoglycemia

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 3 mg	52	—
Oral Semaglutide 7 mg	47	—
Oral Semaglutide 14 mg	48	—
Placebo	54	—

Secondary/registry result

Change in Amylase - Ratio to Baseline

Time frame:Week 0, week 26, week 52

ratio, descriptive

Posted result

Group	Value (geometric_mean), Ratio of amylase	95% CI
Oral Semaglutide 3 mgWeek 26	1.08	—
Week 52	1.07	—
Oral Semaglutide 7 mgWeek 26	1.12	—
Week 52	1.11	—
Oral Semaglutide 14 mgWeek 26	1.14	—
Week 52	1.17	—
PlaceboWeek 26	1.01	—
Week 52	0.99	—

Secondary/registry result

Change in Lipase - Ratio to Baseline

Time frame:Week 0, week 26, week 52

ratio, descriptive

Posted result

Group	Value (geometric_mean), Ratio of lipase	95% CI
Oral Semaglutide 3 mgWeek 26	1.14	—
Week 52	1.09	—
Oral Semaglutide 7 mgWeek 26	1.34	—
Week 52	1.25	—
Oral Semaglutide 14 mgWeek 26	1.35	—
Week 52	1.35	—
PlaceboWeek 26	0.99	—
Week 52	0.99	—

Secondary/registry result

Change in ECG Evaluation

Time frame:Week 0, week 26, week 52

categorical status, descriptive

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 3 mgNormal (week 0) to Normal (week 26)	101	—
Normal (week 0) to Abnormal NCS (week 26)	10	—
Normal (week 0) to Abnormal CS (week 26)	0	—
Abnormal NCS (week 0) to Normal (week 26)	22	—
Abnormal NCS (week 0) to Abnormal NCS (week 26)	44	—
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	—
Normal (week 0) to Normal (week 52)	95	—
Normal (week 0) to Abnormal NCS (week 52)	14	—
Normal (week 0) to Abnormal CS (week 52)	2	—
Abnormal NCS to Normal (Week 52)	13	—
Abnormal NCS to Abnormal NCS (Week 52)	50	—
Abnormal NCS to Abnormal CS (Week 52)	0	—
Abnormal CS to Normal (Week 52)	0	—
Abnormal CS to Abnormal NCS (Week 52)	0	—
Abnormal CS to Abnormal CS (Week 52)	0	—
Oral Semaglutide 7 mgNormal (week 0) to Normal (week 26)	98	—
Normal (week 0) to Abnormal NCS (week 26)	12	—
Normal (week 0) to Abnormal CS (week 26)	0	—
Abnormal NCS (week 0) to Normal (week 26)	17	—
Abnormal NCS (week 0) to Abnormal NCS (week 26)	42	—
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)	4	—
Normal (week 0) to Normal (week 52)	91	—
Normal (week 0) to Abnormal NCS (week 52)	15	—
Normal (week 0) to Abnormal CS (week 52)	2	—
Abnormal NCS to Normal (Week 52)	17	—
Abnormal NCS to Abnormal NCS (Week 52)	40	—
Abnormal NCS to Abnormal CS (Week 52)	1	—
Abnormal CS to Normal (Week 52)	0	—
Abnormal CS to Abnormal NCS (Week 52)	0	—
Abnormal CS to Abnormal CS (Week 52)	4	—
Oral Semaglutide 14 mgNormal (week 0) to Normal (week 26)	90	—
Normal (week 0) to Abnormal NCS (week 26)	17	—
Normal (week 0) to Abnormal CS (week 26)	0	—
Abnormal NCS (week 0) to Normal (week 26)	16	—
Abnormal NCS (week 0) to Abnormal NCS (week 26)	47	—
Abnormal NCS (week 0) to Abnormal CS (week 26)	0	—
Abnormal CS (week 0) to Normal (week 26)	1	—
Abnormal CS (week 0) to Abnormal NCS (week 26)	1	—
Abnormal CS (week 0) to Abnormal CS (week 26)	1	—
Normal (week 0) to Normal (week 52)	85	—
Normal (week 0) to Abnormal NCS (week 52)	20	—
Normal (week 0) to Abnormal CS (week 52)	1	—
Abnormal NCS to Normal (Week 52)	19	—
Abnormal NCS to Abnormal NCS (Week 52)	42	—
Abnormal NCS to Abnormal CS (Week 52)	0	—
Abnormal CS to Normal (Week 52)	0	—
Abnormal CS to Abnormal NCS (Week 52)	2	—
Abnormal CS to Abnormal CS (Week 52)	1	—
PlaceboNormal (week 0) to Normal (week 26)	93	—
Normal (week 0) to Abnormal NCS (week 26)	12	—
Normal (week 0) to Abnormal CS (week 26)	0	—
Abnormal NCS (week 0) to Normal (week 26)	19	—
Abnormal NCS (week 0) to Abnormal NCS (week 26)	51	—
Abnormal NCS (week 0) to Abnormal CS (week 26)	0	—
Abnormal CS (week 0) to Normal (week 26)	1	—
Abnormal CS (week 0) to Abnormal NCS (week 26)	0	—
Abnormal CS (week 0) to Abnormal CS (week 26)	1	—
Normal (week 0) to Normal (week 52)	84	—
Normal (week 0) to Abnormal NCS (week 52)	17	—
Normal (week 0) to Abnormal CS (week 52)	1	—
Abnormal NCS to Normal (Week 52)	21	—
Abnormal NCS to Abnormal NCS (Week 52)	47	—
Abnormal NCS to Abnormal CS (Week 52)	1	—
Abnormal CS to Normal (Week 52)	0	—
Abnormal CS to Abnormal NCS (Week 52)	1	—
Abnormal CS to Abnormal CS (Week 52)	1	—

Secondary/registry result

Change in Physical Examination

Time frame:Week -2, week 52

descriptive

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 3 mg1) Cardiovascular system (week -2)	166	—
1) Cardiovascular system (week -2)	18	—
1) Cardiovascular system (week -2)	0	—
1) Cardiovascular system (week 52)	157	—
1) Cardiovascular system (week 52)	17	—
1) Cardiovascular system (week 52)	0	—
2) Central and peripheral nervous system (week -2)	158	—
2) Central and peripheral nervous system (week -2)	26	—
2) Central and peripheral nervous system (week -2)	0	—
2) Central and peripheral nervous system (week 52)	149	—
2) Central and peripheral nervous system (week 52)	25	—
2) Central and peripheral nervous system (week 52)	0	—
3) Gastrointestinal system, incl. mouth (week -2)	173	—
3) Gastrointestinal system, incl. mouth (week -2)	11	—
3) Gastrointestinal system, incl. mouth (week -2)	0	—
3) Gastrointestinal system, incl. mouth (week 52)	163	—
3) Gastrointestinal system, incl. mouth (week 52)	9	—
3) Gastrointestinal system, incl. mouth (week 52)	2	—
4) General appearance (week -2)	159	—
4) General appearance (week -2)	25	—
4) General appearance (week -2)	0	—
4) General appearance (week 52)	151	—
4) General appearance (week 52)	23	—
4) General appearance (week 52)	0	—
5) Head, ears, eyes, nose, throat, neck (week -2)	168	—
5) Head, ears, eyes, nose, throat, neck (week -2)	15	—
5) Head, ears, eyes, nose, throat, neck (week -2)	1	—
5) Head, ears, eyes, nose, throat, neck (week 52)	161	—
5) Head, ears, eyes, nose, throat, neck (week 52)	13	—
5) Head, ears, eyes, nose, throat, neck (week 52)	0	—
6) Lymph node palpation (week -2)	184	—
6) Lymph node palpation (week -2)	0	—
6) Lymph node palpation (week -2)	0	—
6) Lymph node palpation (week 52)	172	—
6) Lymph node palpation (week 52)	0	—
6) Lymph node palpation (week 52)	0	—
7) Musculoskeletal system (week -2)	171	—
7) Musculoskeletal system (week -2)	13	—
7) Musculoskeletal system (week -2)	0	—
7) Musculoskeletal system (week 52)	160	—
7) Musculoskeletal system (week 52)	11	—
7) Musculoskeletal system (week 52)	3	—
8) Respiratory system (week -2)	182	—
8) Respiratory system (week -2)	1	—
8) Respiratory system (week -2)	1	—
8) Respiratory system (week 52)	173	—
8) Respiratory system (week 52)	1	—
8) Respiratory system (week 52)	0	—
9) Skin (week -2)	156	—
9) Skin (week -2)	27	—
9) Skin (week -2)	1	—
9) Skin (week 52)	152	—
9) Skin (week 52)	20	—
9) Skin (week 52)	2	—
10) Thyroid gland (week -2)	177	—
10) Thyroid gland (week -2)	7	—
10) Thyroid gland (week -2)	0	—
10) Thyroid gland (week 52)	166	—
10) Thyroid gland (week 52)	8	—
10) Thyroid gland (week 52)	0	—
Oral Semaglutide 7 mg1) Cardiovascular system (week -2)	166	—
1) Cardiovascular system (week -2)	15	—
1) Cardiovascular system (week -2)	0	—
1) Cardiovascular system (week 52)	158	—
1) Cardiovascular system (week 52)	12	—
1) Cardiovascular system (week 52)	0	—
2) Central and peripheral nervous system (week -2)	157	—
2) Central and peripheral nervous system (week -2)	24	—
2) Central and peripheral nervous system (week -2)	0	—
2) Central and peripheral nervous system (week 52)	150	—
2) Central and peripheral nervous system (week 52)	20	—
2) Central and peripheral nervous system (week 52)	0	—
3) Gastrointestinal system, incl. mouth (week -2)	175	—
3) Gastrointestinal system, incl. mouth (week -2)	6	—
3) Gastrointestinal system, incl. mouth (week -2)	0	—
3) Gastrointestinal system, incl. mouth (week 52)	164	—
3) Gastrointestinal system, incl. mouth (week 52)	6	—
3) Gastrointestinal system, incl. mouth (week 52)	0	—
4) General appearance (week -2)	162	—
4) General appearance (week -2)	18	—
4) General appearance (week -2)	1	—
4) General appearance (week 52)	148	—
4) General appearance (week 52)	21	—
4) General appearance (week 52)	1	—
5) Head, ears, eyes, nose, throat, neck (week -2)	173	—
5) Head, ears, eyes, nose, throat, neck (week -2)	8	—
5) Head, ears, eyes, nose, throat, neck (week -2)	0	—
5) Head, ears, eyes, nose, throat, neck (week 52)	164	—
5) Head, ears, eyes, nose, throat, neck (week 52)	6	—
5) Head, ears, eyes, nose, throat, neck (week 52)	0	—
6) Lymph node palpation (week -2)	181	—
6) Lymph node palpation (week -2)	0	—
6) Lymph node palpation (week -2)	0	—
6) Lymph node palpation (week 52)	170	—
6) Lymph node palpation (week 52)	0	—
6) Lymph node palpation (week 52)	0	—
7) Musculoskeletal system (week -2)	170	—
7) Musculoskeletal system (week -2)	10	—
7) Musculoskeletal system (week -2)	1	—
7) Musculoskeletal system (week 52)	160	—
7) Musculoskeletal system (week 52)	9	—
7) Musculoskeletal system (week 52)	1	—
8) Respiratory system (week -2)	177	—
8) Respiratory system (week -2)	4	—
8) Respiratory system (week -2)	0	—
8) Respiratory system (week 52)	164	—
8) Respiratory system (week 52)	6	—
8) Respiratory system (week 52)	0	—
9) Skin (week -2)	153	—
9) Skin (week -2)	28	—
9) Skin (week -2)	0	—
9) Skin (week 52)	144	—
9) Skin (week 52)	26	—
9) Skin (week 52)	0	—
10) Thyroid gland (week -2)	176	—
10) Thyroid gland (week -2)	5	—
10) Thyroid gland (week -2)	0	—
10) Thyroid gland (week 52)	165	—
10) Thyroid gland (week 52)	5	—
10) Thyroid gland (week 52)	0	—
Oral Semaglutide 14 mg1) Cardiovascular system (week -2)	157	—
1) Cardiovascular system (week -2)	24	—
1) Cardiovascular system (week -2)	0	—
1) Cardiovascular system (week 52)	145	—
1) Cardiovascular system (week 52)	24	—
1) Cardiovascular system (week 52)	1	—
2) Central and peripheral nervous system (week -2)	158	—
2) Central and peripheral nervous system (week -2)	21	—
2) Central and peripheral nervous system (week -2)	2	—
2) Central and peripheral nervous system (week 52)	147	—
2) Central and peripheral nervous system (week 52)	22	—
2) Central and peripheral nervous system (week 52)	1	—
3) Gastrointestinal system, incl. mouth (week -2)	177	—
3) Gastrointestinal system, incl. mouth (week -2)	4	—
3) Gastrointestinal system, incl. mouth (week -2)	0	—
3) Gastrointestinal system, incl. mouth (week 52)	166	—
3) Gastrointestinal system, incl. mouth (week 52)	3	—
3) Gastrointestinal system, incl. mouth (week 52)	1	—
4) General appearance (week -2)	160	—
4) General appearance (week -2)	21	—
4) General appearance (week -2)	0	—
4) General appearance (week 52)	153	—
4) General appearance (week 52)	17	—
4) General appearance (week 52)	0	—
5) Head, ears, eyes, nose, throat, neck (week -2)	172	—
5) Head, ears, eyes, nose, throat, neck (week -2)	7	—
5) Head, ears, eyes, nose, throat, neck (week -2)	2	—
5) Head, ears, eyes, nose, throat, neck (week 52)	165	—
5) Head, ears, eyes, nose, throat, neck (week 52)	3	—
5) Head, ears, eyes, nose, throat, neck (week 52)	2	—
6) Lymph node palpation (week -2)	181	—
6) Lymph node palpation (week -2)	0	—
6) Lymph node palpation (week -2)	0	—
6) Lymph node palpation (week 52)	170	—
6) Lymph node palpation (week 52)	0	—
6) Lymph node palpation (week 52)	0	—
7) Musculoskeletal system (week -2)	169	—
7) Musculoskeletal system (week -2)	9	—
7) Musculoskeletal system (week -2)	3	—
7) Musculoskeletal system (week 52)	159	—
7) Musculoskeletal system (week 52)	8	—
7) Musculoskeletal system (week 52)	3	—
8) Respiratory system (week -2)	180	—
8) Respiratory system (week -2)	1	—
8) Respiratory system (week -2)	0	—
8) Respiratory system (week 52)	170	—
8) Respiratory system (week 52)	0	—
8) Respiratory system (week 52)	0	—
9) Skin (week -2)	159	—
9) Skin (week -2)	22	—
9) Skin (week -2)	0	—
9) Skin (week 52)	151	—
9) Skin (week 52)	18	—
9) Skin (week 52)	1	—
10) Thyroid gland (week -2)	176	—
10) Thyroid gland (week -2)	5	—
10) Thyroid gland (week -2)	0	—
10) Thyroid gland (week 52)	168	—
10) Thyroid gland (week 52)	2	—
10) Thyroid gland (week 52)	0	—
Placebo1) Cardiovascular system (week -2)	170	—
1) Cardiovascular system (week -2)	14	—
1) Cardiovascular system (week -2)	0	—
1) Cardiovascular system (week 52)	160	—
1) Cardiovascular system (week 52)	12	—
1) Cardiovascular system (week 52)	1	—
2) Central and peripheral nervous system (week -2)	163	—
2) Central and peripheral nervous system (week -2)	21	—
2) Central and peripheral nervous system (week -2)	0	—
2) Central and peripheral nervous system (week 52)	155	—
2) Central and peripheral nervous system (week 52)	18	—
2) Central and peripheral nervous system (week 52)	0	—
3) Gastrointestinal system, incl. mouth (week -2)	180	—
3) Gastrointestinal system, incl. mouth (week -2)	4	—
3) Gastrointestinal system, incl. mouth (week -2)	0	—
3) Gastrointestinal system, incl. mouth (week 52)	171	—
3) Gastrointestinal system, incl. mouth (week 52)	1	—
3) Gastrointestinal system, incl. mouth (week 52)	1	—
4) General appearance (week -2)	162	—
4) General appearance (week -2)	22	—
4) General appearance (week -2)	0	—
4) General appearance (week 52)	152	—
4) General appearance (week 52)	21	—
4) General appearance (week 52)	0	—
5) Head, ears, eyes, nose, throat, neck (week -2)	178	—
5) Head, ears, eyes, nose, throat, neck (week -2)	5	—
5) Head, ears, eyes, nose, throat, neck (week -2)	1	—
5) Head, ears, eyes, nose, throat, neck (week 52)	166	—
5) Head, ears, eyes, nose, throat, neck (week 52)	5	—
5) Head, ears, eyes, nose, throat, neck (week 52)	2	—
6) Lymph node palpation (week -2)	184	—
6) Lymph node palpation (week -2)	0	—
6) Lymph node palpation (week -2)	0	—
6) Lymph node palpation (week 52)	172	—
6) Lymph node palpation (week 52)	1	—
6) Lymph node palpation (week 52)	0	—
7) Musculoskeletal system (week -2)	175	—
7) Musculoskeletal system (week -2)	9	—
7) Musculoskeletal system (week -2)	0	—
7) Musculoskeletal system (week 52)	164	—
7) Musculoskeletal system (week 52)	8	—
7) Musculoskeletal system (week 52)	1	—
8) Respiratory system (week -2)	184	—
8) Respiratory system (week -2)	0	—
8) Respiratory system (week -2)	0	—
8) Respiratory system (week 52)	173	—
8) Respiratory system (week 52)	0	—
8) Respiratory system (week 52)	0	—
9) Skin (week -2)	162	—
9) Skin (week -2)	21	—
9) Skin (week -2)	1	—
9) Skin (week 52)	155	—
9) Skin (week 52)	18	—
9) Skin (week 52)	0	—
10) Thyroid gland (week -2)	177	—
10) Thyroid gland (week -2)	5	—
10) Thyroid gland (week -2)	2	—
10) Thyroid gland (week 52)	166	—
10) Thyroid gland (week 52)	6	—
10) Thyroid gland (week 52)	1	—

Secondary/registry result

Semaglutide Plasma Concentrations for Population PK Analyses

Time frame:Weeks 0-52

Plasma concentration (steady state)

concentration, descriptive

Posted result

Group	Value (geometric_mean), nmol/L	95% CI
Oral Semaglutide 3 mgWeek 4	2.9	—
Week 14	2.9	—
Week 26	2.7	—
Week 38	2.5	—
Week 52	2.4	—
Oral Semaglutide 7 mgWeek 4	2.9	—
Week 14	7.5	—
Week 26	7.2	—
Week 38	6.9	—
Week 52	5.8	—
Oral Semaglutide 14 mgWeek 4	2.9	—
Week 14	14.5	—
Week 26	12.6	—
Week 38	10.8	—
Week 52	11.9	—

Secondary/protocol endpoint

Number of Treatment-emergent Adverse Events (TEAEs) During Exposure to Trial Product

Time frame:Weeks 0-57

Treatment-emergent AEs (any)

event count, event

Secondary/protocol endpoint

Number of Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes

Time frame:Weeks 0-57

Documented hypoglycemia

event count, event

componentsSevere hypoglycemia, Documented hypoglycemia

Secondary/protocol endpoint

Participants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes

Time frame:Weeks 0-57

Severe hypoglycemia

threshold achievement, event

componentsSevere hypoglycemia, Documented hypoglycemia

Secondary/protocol endpoint

Change in Amylase - Ratio to Baseline

Time frame:Week 0, week 26, week 52

ratio, descriptive

Secondary/protocol endpoint

Change in Lipase - Ratio to Baseline

Time frame:Week 0, week 26, week 52

ratio, descriptive

Secondary/protocol endpoint

Change in ECG Evaluation

Time frame:Week 0, week 26, week 52

categorical status, descriptive

Secondary/protocol endpoint

Change in Physical Examination

Time frame:Week -2, week 52

descriptive

Secondary/protocol endpoint

Semaglutide Plasma Concentrations for Population PK Analyses

Time frame:Weeks 0-52

Plasma concentration (steady state)

concentration, descriptive

Other clinical outcomes

2 endpoints

Secondary/registry result

Change in Eye Examination Category

Time frame:Week -2, week 52

categorical status, improvement

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 3 mgLeft eye (week -2)	89	—
Left eye (week -2)	76	—
Left eye (week -2)	19	—
Left eye (week 52)	83	—
Left eye (week 52)	65	—
Left eye (week 52)	22	—
Right eye (week -2)	85	—
Right eye (week -2)	76	—
Right eye (week -2)	23	—
Right eye (week 52)	79	—
Right eye (week 52)	67	—
Right eye (week 52)	23	—
Oral Semaglutide 7 mgLeft eye (week -2)	102	—
Left eye (week -2)	64	—
Left eye (week -2)	14	—
Left eye (week 52)	102	—
Left eye (week 52)	51	—
Left eye (week 52)	14	—
Right eye (week -2)	104	—
Right eye (week -2)	63	—
Right eye (week -2)	13	—
Right eye (week 52)	99	—
Right eye (week 52)	54	—
Right eye (week 52)	14	—
Oral Semaglutide 14 mgLeft eye (week -2)	99	—
Left eye (week -2)	64	—
Left eye (week -2)	18	—
Left eye (week 52)	92	—
Left eye (week 52)	52	—
Left eye (week 52)	18	—
Right eye (week -2)	99	—
Right eye (week -2)	64	—
Right eye (week -2)	18	—
Right eye (week 52)	97	—
Right eye (week 52)	51	—
Right eye (week 52)	15	—
PlaceboLeft eye (week -2)	108	—
Left eye (week -2)	55	—
Left eye (week -2)	21	—
Left eye (week 52)	88	—
Left eye (week 52)	53	—
Left eye (week 52)	25	—
Right eye (week -2)	106	—
Right eye (week -2)	58	—
Right eye (week -2)	20	—
Right eye (week 52)	90	—
Right eye (week 52)	50	—
Right eye (week 52)	26	—

Secondary/protocol endpoint

Change in Eye Examination Category

Time frame:Week -2, week 52

categorical status, improvement

Publications (5)

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

Oral Semaglutide Reduces HbA(1c) and Body Weight in Patients with Type 2 Diabetes Regardless of Background Glucose-Lowering Medication: PIONEER Subgroup Analyses.
Diabetes therapy : research, treatment and education of diabetes and related disorders2021 Apr (month)PMID33660198doi:10.1007/s13300-020-00994-9via clinicaltrials gov reference derived + pubmed nct search
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
Efficacy, Safety, and Tolerability of Oral Semaglutide Versus Placebo Added to Insulin With or Without Metformin in Patients With Type 2 Diabetes: The PIONEER 8 Trial.
Diabetes care2019 Dec (month)PMID31530667doi:10.2337/dc19-0898via CT.gov reference + 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.