PIONEER 10

CompletedPhase 3Results posted

Safety and Efficacy of Oral Semaglutide Versus Dulaglutide Both in Combination With One OAD (Oral Antidiabetic Drug) in Japanese Subjects With Type 2 Diabetes

Safety and Efficacy of Oral Semaglutide Versus Dulaglutide Both in Combination With One OAD in Japanese Subjects With Type 2 Diabetes

Lead sponsor

Novo Nordisk A/S

Assets

Dulaglutide / Semaglutide

Listed sites

Recruiting sites

—

Enrollment

458

actual

Study population

Type 2 diabetes

Key I/E criterion

•HbA1c 7-10.5%

Primary endpoint

•Treatment-emergent AEs (any)

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 IDNCT03015220

Org study IDNN9924-4282

Secondary IDJapicCTI-173485Japic

Secondary IDU1111-1181-4133WHO

Timeline

Milestones

Study first posted2017-01-09estimated

Study start2017-01-10actual

Primary completion2018-07-12actual

Study completion2018-07-12actual

Results first posted2019-12-30actual

Last update posted2021-03-02actual

Assets

Investigational agents

Dulaglutide Semaglutide

Study populations

Who this study enrolls

Type 2 diabetes

Eligibility

Who can enroll

Minimum age20 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial

•Japanese male or female, age above or equal to 20 years at the time of signing informed consent

•Diagnosed with type 2 diabetes mellitus for at least 60 days prior to day of screening

•HbA1c (glycosylated haemoglobin) between 7.0%-10.5% (53-91 mmol/mol) (both inclusive)

•OAD (oral antidiabetic drug) monotherapy with stable daily dose for at least 60 days prior to the day of screening of one of SU (sulphonylurea) glinide , TZD (thiazolidinedione), α-GI (alpha-glucosidase inhibitor) or SGLT-2 (sodium-glucose cotransporter-2) inhibitor according to Japanese labelling

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 measures are abstinence (not having sex), diaphragm, condom (by the partner), intrauterine device, sponge, spermicide or oral contraceptives

•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 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 (TIA) within the past 180 days prior to the day of screening and randomisation

•Subjects presently classified as being in New York Heart Association (NYHA) Class IV

•Planned coronary, carotid or peripheral artery revascularisation known on the day of screening

•Subjects with alanine aminotransferase (ALT) above 2.5 x upper normal limit (UNL)

•Renal impairment defined as estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m^2 as per Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI)

•Treatment with once-weekly glucagon-like peptide-1 receptor agonists (GLP-1 RA) or once weekly dipeptidyl peptidase-4 (DPP-4) inhibitor in a period of 90 days before the day of screening

•For subjects treated with an OAD other than TZD at screening: Treatment with TZD in a period of 90 days before the day of screening

•Treatment with any medication for the indication of diabetes or obesity in addition to background OAD medication (SU, glinide, TZD, α-GI or SGLT-2 inhibitor) in a period of 60 days before the day of screening with the exception of short-term insulin treatment for acute illness for a total of at least 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)

•History of diabetic ketoacidosis

Endpoints (66)

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

Cardiometabolic biomarkers

Safety / tolerability / PK

Weight & body composition

Patient-reported / QoL

Other clinical outcomes

Weight & body composition

12 endpoints

Secondary/registry result

Change in Body Weight (kg)

Time frame:Week 0, week 26, week 52

Body weight, absolute change (kg)

change from baseline, improvement

Posted result

Group	Value (mean), kg	95% CI
Oral Semaglutide 3 mgWeek 26	-0.1	—
Week 52	0.0	—
Oral Semaglutide 7 mgWeek 26	-1.0	—
Week 52	-0.9	—
Oral Semaglutide 14 mgWeek 26	-2.2	—
Week 52	-1.7	—
Dulaglutide 0.75 mgWeek 26	0.3	—
Week 52	1.0	—

Secondary/registry result

Change in Body Weight (%)

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	-0.28	—
Week 52	-0.02	—
Oral Semaglutide 7 mgWeek 26	-1.49	—
Week 52	-1.34	—
Oral Semaglutide 14 mgWeek 26	-3.21	—
Week 52	-2.33	—
Dulaglutide 0.75 mgWeek 26	0.25	—
Week 52	1.25	—

Secondary/registry result

Change in Body Mass Index (BMI)

Time frame:Week 0, week 26, week 52

BMI, change

change from baseline, improvement

Posted result

Group	Value (mean), Kilogram per square meter (kg/m^2)	95% CI
Oral Semaglutide 3 mgWeek 26	-0.1	—
Week 52	-0.0	—
Oral Semaglutide 7 mgWeek 26	-0.4	—
Week 52	-0.3	—
Oral Semaglutide 14 mgWeek 26	-0.8	—
Week 52	-0.6	—
Dulaglutide 0.75 mgWeek 26	0.1	—
Week 52	0.3	—

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), Centimeters (cm)	95% CI
Oral Semaglutide 3 mgWeek 26	0.0	—
Week 52	-0.1	—
Oral Semaglutide 7 mgWeek 26	-0.6	—
Week 52	-0.8	—
Oral Semaglutide 14 mgWeek 26	-1.2	—
Week 52	-1.7	—
Dulaglutide 0.75 mgWeek 26	0.3	—
Week 52	0.7	—

Secondary/registry result

Participants Who Achieve Weight Loss More Than or Equal to 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	6	—
Week 26	122	—
Week 52	7	—
Week 52	120	—
Oral Semaglutide 7 mgWeek 26	23	—
Week 26	105	—
Week 52	21	—
Week 52	108	—
Oral Semaglutide 14 mgWeek 26	39	—
Week 26	89	—
Week 52	28	—
Week 52	99	—
Dulaglutide 0.75 mgWeek 26	4	—
Week 26	60	—
Week 52	4	—
Week 52	59	—

Secondary/registry result

Participants Who Achieve Weight Loss More Than or Equal to 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	0	—
Week 26	128	—
Week 52	0	—
Week 52	127	—
Oral Semaglutide 7 mgWeek 26	6	—
Week 26	122	—
Week 52	9	—
Week 52	120	—
Oral Semaglutide 14 mgWeek 26	8	—
Week 26	120	—
Week 52	7	—
Week 52	120	—
Dulaglutide 0.75 mgWeek 26	1	—
Week 26	63	—
Week 52	0	—
Week 52	63	—

Secondary/protocol endpoint

Change in Body Weight (kg)

Time frame:Week 0, week 26, week 52

Body weight, absolute change (kg)

change from baseline, improvement

Secondary/protocol endpoint

Change in Body Weight (%)

Time frame:Week 0, week 26, week 52

Body weight, % change

percent change from baseline, improvement

Secondary/protocol endpoint

Change in Body Mass Index (BMI)

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 Weight Loss More Than or Equal to 5% (Yes/No).

Time frame:Week 26, week 52

≥5% weight-loss responders

threshold achievement, improvement

Secondary/protocol endpoint

Participants Who Achieve Weight Loss More Than or Equal to 10% (Yes/No)

Time frame:Week 26, week 52

≥10% weight-loss responders

threshold achievement, improvement

Glycemic / diabetes

20 endpoints

Secondary/registry result

Change in HbA1c

Time frame:Week 0, week 26, week 52

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Posted result

Group	Value (mean), Percentage of HbA1c	95% CI
Oral Semaglutide 3 mgWeek 26	-1.1	—
Week 52	-0.8	—
Oral Semaglutide 7 mgWeek 26	-1.7	—
Week 52	-1.4	—
Oral Semaglutide 14 mgWeek 26	-2.0	—
Week 52	-1.8	—
Dulaglutide 0.75 mgWeek 26	-1.6	—
Week 52	-1.4	—

Secondary/registry result

Change in Fasting Plasma Glucose

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	-1.23	—
Week 52	-0.95	—
Oral Semaglutide 7 mgWeek 26	-2.25	—
Week 52	-1.96	—
Oral Semaglutide 14 mgWeek 26	-2.72	—
Week 52	-2.18	—
Dulaglutide 0.75 mgWeek 26	-2.22	—
Week 52	-1.80	—

Secondary/registry result

Change in Self-measured Plasma Glucose 7-point Profile (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	-1.8	—
Week 52	-1.7	—
Oral Semaglutide 7 mgWeek 26	-2.7	—
Week 52	-2.5	—
Oral Semaglutide 14 mgWeek 26	-3.5	—
Week 52	-3.3	—
Dulaglutide 0.75 mgWeek 26	-2.9	—
Week 52	-2.6	—

Secondary/registry result

Change in Self-measured Plasma Glucose (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	-0.9	—
Week 52	-0.6	—
Oral Semaglutide 7 mgWeek 26	-1.3	—
Week 52	-0.8	—
Oral Semaglutide 14 mgWeek 26	-1.2	—
Week 52	-0.9	—
Dulaglutide 0.75 mgWeek 26	-0.7	—
Week 52	-0.7	—

Secondary/registry result

Participants Who Achieve HbA1c Below 7% (53 mmol/Mol), American Diabetes Association 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	59	—
Week 26	69	—
Week 52	43	—
Week 52	83	—
Oral Semaglutide 7 mgWeek 26	96	—
Week 26	32	—
Week 52	77	—
Week 52	52	—
Oral Semaglutide 14 mgWeek 26	105	—
Week 26	23	—
Week 52	90	—
Week 52	37	—
Dulaglutide 0.75 mgWeek 26	45	—
Week 26	19	—
Week 52	32	—
Week 52	31	—

Secondary/registry result

Participants Who Achieve HbA1c Below or Equal to 6.5% (48 mmol/Mol), American Association of Clinical Endocrinologists 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	40	—
Week 26	88	—
Week 52	22	—
Week 52	104	—
Oral Semaglutide 7 mgWeek 26	67	—
Week 26	61	—
Week 52	50	—
Week 52	79	—
Oral Semaglutide 14 mgWeek 26	88	—
Week 26	40	—
Week 52	69	—
Week 52	58	—
Dulaglutide 0.75 mgWeek 26	31	—
Week 26	33	—
Week 52	23	—
Week 52	40	—

Secondary/registry result

Participants Who Achieve HbA1c Below 7.0% (53 mmol/Mol) Without Severe or Blood Glucose Confirmed Symptomatic Hypoglycaemia Episodes and no Weight Gain (Yes/No)

Time frame:Week 26, week 52

HbA1c <7.0% achievement

threshold achievement, improvement

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

LOINC 4548-4

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 3 mgWeek 26	39	—
Week 26	89	—
Week 52	23	—
Week 52	103	—
Oral Semaglutide 7 mgWeek 26	63	—
Week 26	65	—
Week 52	53	—
Week 52	76	—
Oral Semaglutide 14 mgWeek 26	84	—
Week 26	44	—
Week 52	71	—
Week 52	56	—
Dulaglutide 0.75 mgWeek 26	25	—
Week 26	39	—
Week 52	16	—
Week 52	47	—

Secondary/registry result

Participants Who Achieve HbA1c Reduction More Than or Equal to 1% (10.9 mmol/Mol) and Weight Loss More Than or Equal to 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	15	—
Week 26	113	—
Week 52	11	—
Week 52	115	—
Oral Semaglutide 7 mgWeek 26	34	—
Week 26	94	—
Week 52	32	—
Week 52	97	—
Oral Semaglutide 14 mgWeek 26	62	—
Week 26	66	—
Week 52	42	—
Week 52	85	—
Dulaglutide 0.75 mgWeek 26	8	—
Week 26	56	—
Week 52	7	—
Week 52	56	—

Secondary/registry result

Time to Additional Anti-diabetic Medication

Time frame:Weeks 0-52

time to event, event

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 3 mgWeek 0 to week 26	1	—
Week 0 to week 52	24	—
Oral Semaglutide 7 mgWeek 0 to week 26	3	—
Week 0 to week 52	13	—
Oral Semaglutide 14 mgWeek 0 to week 26	6	—
Week 0 to week 52	8	—
Dulaglutide 0.75 mgWeek 0 to week 26	1	—
Week 0 to week 52	8	—

Hazard Ratio (HR)1.5095% CI0.70 – 3.20p0.2963Regression, Cox

Hazard Ratio (HR)0.8095% CI0.35 – 1.83p0.5997Regression, Cox

Hazard Ratio (HR)0.5595% CI0.23 – 1.33p0.1871Regression, 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 to week 26	0	—
Week 0 to week 52	22	—
Oral Semaglutide 7 mgWeek 0 to week 26	0	—
Week 0 to week 52	8	—
Oral Semaglutide 14 mgWeek 0 to week 26	1	—
Week 0 to week 52	2	—
Dulaglutide 0.75 mgWeek 0 to week 26	1	—
Week 0 to week 52	6	—

Hazard Ratio (HR)1.9095% CI0.76 – 4.72p0.1672Regression, Cox

Hazard Ratio (HR)0.6095% CI0.21 – 1.72p0.3391Regression, Cox

Hazard Ratio (HR)0.1295% CI0.02 – 0.62p0.0110Regression, Cox

Secondary/protocol endpoint

Change in HbA1c

Time frame:Week 0, week 26, week 52

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Secondary/protocol endpoint

Change in Fasting Plasma Glucose

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 7-point Profile (SMPG) - Mean 7-point Profile

Time frame:Week 0, week 26, week 52

Postprandial glucose

change from baseline, improvement

Secondary/protocol endpoint

Change in Self-measured Plasma Glucose (SMPG) - Mean Postprandial Increment Over All Meals

Time frame:Week 0, week 26, week 52

Postprandial glucose

change from baseline, improvement

Secondary/protocol endpoint

Participants Who Achieve HbA1c Below 7% (53 mmol/Mol), American Diabetes Association 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 Below or Equal to 6.5% (48 mmol/Mol), American Association of Clinical Endocrinologists 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 Below 7.0% (53 mmol/Mol) Without Severe or Blood Glucose Confirmed Symptomatic Hypoglycaemia Episodes 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 More Than or Equal to 1% (10.9 mmol/Mol) and Weight Loss More Than or Equal to 3% (Yes/No)

Time frame:Week 26, week 52

threshold achievement, improvement

componentsHbA1c, change, Body weight, % change

Secondary/protocol endpoint/low confidence

Time to Additional Anti-diabetic Medication

Time frame:Weeks 0-52

time to event, event

Secondary/protocol endpoint

Time to Rescue Medication

Time frame:Weeks 0-52

time to event, event

Cardiometabolic biomarkers

14 endpoints

Secondary/registry result

Change in Fasting 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 fasting total cholesterol	95% CI
Oral Semaglutide 3 mgWeek 26	0.96	—
Week 52	0.98	—
Oral Semaglutide 7 mgWeek 26	0.91	—
Week 52	0.95	—
Oral Semaglutide 14 mgWeek 26	0.91	—
Week 52	0.94	—
Dulaglutide 0.75 mgWeek 26	0.92	—
Week 52	0.93	—

Secondary/registry result

Change in Fasting Low-density Lipoprotein (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 fasting LDL	95% CI
Oral Semaglutide 3 mgWeek 26	0.92	—
Week 52	0.98	—
Oral Semaglutide 7 mgWeek 26	0.88	—
Week 52	0.94	—
Oral Semaglutide 14 mgWeek 26	0.87	—
Week 52	0.92	—
Dulaglutide 0.75 mgWeek 26	0.88	—
Week 52	0.91	—

Secondary/registry result

Change in Fasting High-density Lipoprotein (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 fasting HDL	95% CI
Oral Semaglutide 3 mgWeek 26	1.02	—
Week 52	1.03	—
Oral Semaglutide 7 mgWeek 26	0.99	—
Week 52	0.99	—
Oral Semaglutide 14 mgWeek 26	1.00	—
Week 52	1.01	—
Dulaglutide 0.75 mgWeek 26	0.99	—
Week 52	1.00	—

Secondary/registry result

Change in Fasting Very-low Density Lipoprotein (VLDL) - Cholesterol (Ratio to Baseline)

Time frame:Week 0, week 26, week 52

VLDL, change

ratio, improvement

Posted result

Group	Value (geometric_mean), Ratio of fasting VLDL	95% CI
Oral Semaglutide 3 mgWeek 26	1.03	—
Week 52	0.90	—
Oral Semaglutide 7 mgWeek 26	0.92	—
Week 52	0.87	—
Oral Semaglutide 14 mgWeek 26	0.96	—
Week 52	0.86	—
Dulaglutide 0.75 mgWeek 26	0.93	—
Week 52	0.88	—

Secondary/registry result

Change in Fasting Triglyceride (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 fasting triglycerides	95% CI
Oral Semaglutide 3 mgWeek 26	1.03	—
Week 52	0.89	—
Oral Semaglutide 7 mgWeek 26	0.91	—
Week 52	0.87	—
Oral Semaglutide 14 mgWeek 26	0.96	—
Week 52	0.87	—
Dulaglutide 0.75 mgWeek 26	0.93	—
Week 52	0.88	—

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 per minute (beats/min)	95% CI
Oral Semaglutide 3 mgWeek 26	3	—
Week 52	3	—
Oral Semaglutide 7 mgWeek 26	4	—
Week 52	3	—
Oral Semaglutide 14 mgWeek 26	4	—
Week 52	3	—
Dulaglutide 0.75 mgWeek 26	4	—
Week 52	2	—

Secondary/registry result

Change in Blood Pressure

Time frame:Week 0, week 26, week 52

change from baseline, improvement

Posted result

Group	Value (mean), Millimeters of mercury (mmHg)	95% CI
Oral Semaglutide 3 mgWeek 26: SBP	-3.0	—
Week 52: SBP	-2.0	—
Week 26: DBP	-1.0	—
Week 52: DBP	0.0	—
Oral Semaglutide 7 mgWeek 26: SBP	-5.0	—
Week 52: SBP	-2.0	—
Week 26: DBP	-1.0	—
Week 52: DBP	0.0	—
Oral Semaglutide 14 mgWeek 26: SBP	-6.0	—
Week 52: SBP	-2.0	—
Week 26: DBP	-2.0	—
Week 52: DBP	-1.0	—
Dulaglutide 0.75 mgWeek 26: SBP	-4.0	—
Week 52: SBP	-3.0	—
Week 26: DBP	-1.0	—
Week 52: DBP	0.0	—

Secondary/protocol endpoint

Change in Fasting 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 Fasting Low-density Lipoprotein (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 Fasting High-density Lipoprotein (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 Fasting Very-low Density Lipoprotein (VLDL) - Cholesterol (Ratio to Baseline)

Time frame:Week 0, week 26, week 52

VLDL, change

ratio, improvement

Secondary/protocol endpoint

Change in Fasting Triglyceride (Ratio to Baseline)

Time frame:Week 0, week 26, week 52

Triglycerides, change

ratio, improvement

LOINC 2571-8

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 Blood Pressure

Time frame:Week 0, week 26, week 52

change from baseline, improvement

Patient-reported / QoL

4 endpoints

Secondary/registry result

Change in SF-36v2 (Acute Version) Health Survey Scores: 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)	-0.18	—
1) Physical functioning (week 52)	-0.37	—
2) Role Physical (week 26)	-0.58	—
2) Role Physical (week 52)	-0.92	—
3) Bodily Pain (week 26)	-0.88	—
3) Bodily Pain (week 52)	-2.72	—
4)General Health (week 26)	0.42	—
4)General Health (week 52)	-0.34	—
5) Vitality (week 26)	-1.62	—
5) Vitality (week 52)	-0.90	—
6) Social functioning (week 26)	-0.77	—
6) Social functioning (week 52)	-1.98	—
7) Role emotional (week 26)	-0.54	—
7) Role emotional (week 52)	-1.02	—
8) Mental health (week 26)	-1.03	—
8) Mental health (week 52)	-1.64	—
Physical component summary (week 26)	-0.17	—
Physical component summary (week 52)	-0.88	—
Mental component summary (week 26)	-1.13	—
Mental component summary (week 52)	-1.52	—
Oral Semaglutide 7 mg1) Physical functioning (week 26)	0.08	—
1) Physical functioning (week 52)	0.70	—
2) Role Physical (week 26)	0.59	—
2) Role Physical (week 52)	0.05	—
3) Bodily Pain (week 26)	0.05	—
3) Bodily Pain (week 52)	-0.27	—
4)General Health (week 26)	0.09	—
4)General Health (week 52)	0.01	—
5) Vitality (week 26)	-0.79	—
5) Vitality (week 52)	-0.11	—
6) Social functioning (week 26)	-0.15	—
6) Social functioning (week 52)	-0.42	—
7) Role emotional (week 26)	0.42	—
7) Role emotional (week 52)	0.59	—
8) Mental health (week 26)	0.16	—
8) Mental health (week 52)	-0.35	—
Physical component summary (week 26)	0.14	—
Physical component summary (week 52)	0.19	—
Mental component summary (week 26)	-0.07	—
Mental component summary (week 52)	-0.19	—
Oral Semaglutide 14 mg1) Physical functioning (week 26)	-0.06	—
1) Physical functioning (week 52)	-0.02	—
2) Role Physical (week 26)	-1.01	—
2) Role Physical (week 52)	-0.92	—
3) Bodily Pain (week 26)	-0.99	—
3) Bodily Pain (week 52)	0.01	—
4)General Health (week 26)	0.71	—
4)General Health (week 52)	0.59	—
5) Vitality (week 26)	-0.83	—
5) Vitality (week 52)	0.09	—
6) Social functioning (week 26)	-0.15	—
6) Social functioning (week 52)	-0.12	—
7) Role emotional (week 26)	-1.16	—
7) Role emotional (week 52)	-1.05	—
8) Mental health (week 26)	-0.41	—
8) Mental health (week 52)	0.27	—
Physical component summary (week 26)	-0.23	—
Physical component summary (week 52)	-0.03	—
Mental component summary (week 26)	-0.71	—
Mental component summary (week 52)	-0.23	—
Dulaglutide 0.75 mg1) Physical functioning (week 26)	-0.24	—
1) Physical functioning (week 52)	-0.61	—
2) Role Physical (week 26)	-0.48	—
2) Role Physical (week 52)	-0.28	—
3) Bodily Pain (week 26)	-0.44	—
3) Bodily Pain (week 52)	0.24	—
4)General Health (week 26)	-1.03	—
4)General Health (week 52)	-0.97	—
5) Vitality (week 26)	-1.40	—
5) Vitality (week 52)	-0.86	—
6) Social functioning (week 26)	0.15	—
6) Social functioning (week 52)	-0.08	—
7) Role emotional (week 26)	-1.01	—
7) Role emotional (week 52)	-1.21	—
8) Mental health (week 26)	0.27	—
8) Mental health (week 52)	-0.31	—
Physical component summary (week 26)	-0.57	—
Physical component summary (week 52)	-0.24	—
Mental component summary (week 26)	-0.42	—
Mental component summary (week 52)	-0.74	—

Secondary/registry result

Diabetes Therapy-Related Quality of Life (DTR-QoL): Total Score and Scores for the 4 Domains

Time frame:week 0, week 26, week 52

descriptive, improvement

Posted result

Group	Value (mean), Score on a scale	95% CI
Oral Semaglutide 3 mg1.Burden on social and daily activities (W26)	6.44	—
1.Burden on social and daily activities (W52)	4.73	—
2.Anxiety and dissatisfaction with treatment(W26)	6.54	—
2.Anxiety and dissatisfaction with treatment(W52)	0.98	—
3.Hypoglycemia (W26)	5.18	—
3.Hypoglycemia (W52)	4.20	—
4.Satisfaction with treatment(W26)	9.67	—
4.Satisfaction with treatment(W52)	2.46	—
Total score(W26)	6.74	—
Total score(W52)	3.31	—
Oral Semaglutide 7 mg1.Burden on social and daily activities (W26)	6.93	—
1.Burden on social and daily activities (W52)	6.81	—
2.Anxiety and dissatisfaction with treatment(W26)	10.94	—
2.Anxiety and dissatisfaction with treatment(W52)	9.93	—
3.Hypoglycemia (W26)	1.95	—
3.Hypoglycemia (W52)	1.94	—
4.Satisfaction with treatment(W26)	10.81	—
4.Satisfaction with treatment(W52)	7.88	—
Total score(W26)	7.88	—
Total score(W52)	7.15	—
Oral Semaglutide 14 mg1.Burden on social and daily activities (W26)	4.88	—
1.Burden on social and daily activities (W52)	5.44	—
2.Anxiety and dissatisfaction with treatment(W26)	12.24	—
2.Anxiety and dissatisfaction with treatment(W52)	11.37	—
3.Hypoglycemia (W26)	2.67	—
3.Hypoglycemia (W52)	3.87	—
4.Satisfaction with treatment(W26)	14.29	—
4.Satisfaction with treatment(W52)	15.49	—
Total score(W26)	7.90	—
Total score(W52)	8.25	—
Dulaglutide 0.75 mg1.Burden on social and daily activities (W26)	5.29	—
1.Burden on social and daily activities (W52)	3.99	—
2.Anxiety and dissatisfaction with treatment(W26)	9.24	—
2.Anxiety and dissatisfaction with treatment(W52)	3.14	—
3.Hypoglycemia (W26)	3.26	—
3.Hypoglycemia (W52)	-0.66	—
4.Satisfaction with treatment(W26)	13.15	—
4.Satisfaction with treatment(W52)	6.35	—
Total score(W26)	7.18	—
Total score(W52)	3.44	—

Secondary/protocol endpoint

Change in SF-36v2 (Acute Version) Health Survey Scores: 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

Diabetes Therapy-Related Quality of Life (DTR-QoL): Total Score and Scores for the 4 Domains

Time frame:week 0, week 26, week 52

change from baseline, improvement

Safety / tolerability / PK

14 endpoints

Primary/registry result

Number of Treatment-emergent Adverse Events (TEAEs)

Time frame:Weeks 0-57

Treatment-emergent AEs (any)

event count, event

Posted result

Group	Value (number), Events	95% CI
Oral Semaglutide 3 mg	330	—
Oral Semaglutide 7 mg	350	—
Oral Semaglutide 14 mg	324	—
Dulaglutide 0.75 mg	178	—

Primary/protocol endpoint

Number of Treatment-emergent Adverse Events (TEAEs)

Time frame:Weeks 0-57

Treatment-emergent AEs (any)

event count, event

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	1.01	—
Week 52	1.03	—
Oral Semaglutide 7 mgWeek 26	1.07	—
Week 52	1.10	—
Oral Semaglutide 14 mgWeek 26	1.10	—
Week 52	1.11	—
Dulaglutide 0.75 mgWeek 26	1.05	—
Week 52	1.07	—

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	1.15	—
Week 52	1.11	—
Oral Semaglutide 7 mgWeek 26	1.27	—
Week 52	1.36	—
Oral Semaglutide 14 mgWeek 26	1.40	—
Week 52	1.40	—
Dulaglutide 0.75 mgWeek 26	1.14	—
Week 52	1.15	—

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)	103	—
Normal (week 0) to abnormal NCS (week 26)	4	—
Normal (week 0) to abnormal CS (week 26)	2	—
Abnormal NCS (week 0) to normal (week 26)	0	—
Abnormal NCS (week 0) to abnormal NCS (week 26)	16	—
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)	2	—
Normal (week 0) to normal (week 52)	103	—
Normal (week 0) to abnormal NCS (week 52)	3	—
Normal (week 0) to abnormal CS (week 52)	2	—
Abnormal (week 0) NCS to normal (week 52)	2	—
Abnormal (week 0) NCS to abnormal NCS (week 52)	13	—
Abnormal (week 0) NCS to abnormal CS (week 52)	0	—
Abnormal (week 0) CS to normal (week 52)	1	—
Abnormal (week 0) CS to abnormal NCS (week 52)	0	—
Abnormal (week 0) CS to abnormal CS (week 52)	3	—
Oral Semaglutide 7 mgNormal (week 0) to normal (week 26)	110	—
Normal (week 0) to abnormal NCS (week 26)	3	—
Normal (week 0) to abnormal CS (week 26)	0	—
Abnormal NCS (week 0) to normal (week 26)	3	—
Abnormal NCS (week 0) to abnormal NCS (week 26)	12	—
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)	1	—
Normal (week 0) to normal (week 52)	108	—
Normal (week 0) to abnormal NCS (week 52)	5	—
Normal (week 0) to abnormal CS (week 52)	0	—
Abnormal (week 0) NCS to normal (week 52)	5	—
Abnormal (week 0) NCS to abnormal NCS (week 52)	10	—
Abnormal (week 0) NCS to abnormal CS (week 52)	0	—
Abnormal (week 0) CS to normal (week 52)	1	—
Abnormal (week 0) CS to abnormal NCS (week 52)	0	—
Abnormal (week 0) CS to abnormal CS (week 52)	0	—
Oral Semaglutide 14 mgNormal (week 0) to normal (week 26)	99	—
Normal (week 0) to abnormal NCS (week 26)	3	—
Normal (week 0) to abnormal CS (week 26)	0	—
Abnormal NCS (week 0) to normal (week 26)	4	—
Abnormal NCS (week 0) to abnormal NCS (week 26)	18	—
Abnormal NCS (week 0) to abnormal CS (week 26)	2	—
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)	2	—
Normal (week 0) to normal (week 52)	95	—
Normal (week 0) to abnormal NCS (week 52)	6	—
Normal (week 0) to abnormal CS (week 52)	1	—
Abnormal (week 0) NCS to normal (week 52)	6	—
Abnormal (week 0) NCS to abnormal NCS (week 52)	18	—
Abnormal (week 0) NCS to abnormal CS (week 52)	0	—
Abnormal (week 0) CS to normal (week 52)	0	—
Abnormal (week 0) CS to abnormal NCS (week 52)	0	—
Abnormal (week 0) CS to abnormal CS (week 52)	1	—
Dulaglutide 0.75 mgNormal (week 0) to normal (week 26)	54	—
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)	2	—
Abnormal NCS (week 0) to abnormal NCS (week 26)	4	—
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)	55	—
Normal (week 0) to abnormal NCS (week 52)	2	—
Normal (week 0) to abnormal CS (week 52)	0	—
Abnormal (week 0) NCS to normal (week 52)	3	—
Abnormal (week 0) NCS to abnormal NCS (week 52)	3	—
Abnormal (week 0) NCS to abnormal CS (week 52)	0	—
Abnormal (week 0) CS to normal (week 52)	0	—
Abnormal (week 0) CS to abnormal NCS (week 52)	0	—
Abnormal (week 0) CS to abnormal CS (week 52)	0	—

Secondary/registry result

Change in Physical Examination

Time frame:Week -2, week 26, week 52

descriptive

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 3 mg1) Cardiovascular system (week -2)	128	—
1) Cardiovascular system (week -2)	1	—
1) Cardiovascular system (week -2)	2	—
1) Cardiovascular system (week 26)	125	—
1) Cardiovascular system (week 26)	0	—
1) Cardiovascular system (week 26)	3	—
1) Cardiovascular system (week 52)	124	—
1) Cardiovascular system (week 52)	1	—
1) Cardiovascular system (week 52)	2	—
2) Central and peripheral nervous system (week -2)	131	—
2) Central and peripheral nervous system (week -2)	0	—
2) Central and peripheral nervous system (week -2)	0	—
2) Central and peripheral nervous system (week 26)	128	—
2) Central and peripheral nervous system (week 26)	0	—
2) Central and peripheral nervous system (week 26)	0	—
2) Central and peripheral nervous system (week 56)	127	—
2) Central and peripheral nervous system (week 56)	0	—
2) Central and peripheral nervous system (week 56)	0	—
3) Gastrointestinal system, incl. mouth (week -2)	126	—
3) Gastrointestinal system, incl. mouth (week -2)	0	—
3) Gastrointestinal system, incl. mouth (week -2)	5	—
3) Gastrointestinal system, incl. mouth (week 26)	122	—
3) Gastrointestinal system, incl. mouth (week 26)	0	—
3) Gastrointestinal system, incl. mouth (week 26)	6	—
3) Gastrointestinal system, incl. mouth (week 52)	122	—
3) Gastrointestinal system, incl. mouth (week 52)	1	—
3) Gastrointestinal system, incl. mouth (week 52)	4	—
4.General appearance (week -2)	131	—
4.General appearance (week -2)	0	—
4.General appearance (week -2)	0	—
4.General appearance (week 26)	127	—
4.General appearance (week 26)	1	—
4.General appearance (week 26)	0	—
4.General appearance (week 52)	126	—
4.General appearance (week 52)	0	—
4.General appearance (week 52)	1	—
5.Head, ears, eyes, nose, throat, neck (week -2)	121	—
5.Head, ears, eyes, nose, throat, neck (week -2)	3	—
5.Head, ears, eyes, nose, throat, neck (week -2)	7	—
5.Head, ears, eyes, nose, throat, neck (week 26)	119	—
5.Head, ears, eyes, nose, throat, neck (week 26)	4	—
5.Head, ears, eyes, nose, throat, neck (week 26)	5	—
5.Head, ears, eyes, nose, throat, neck (week 52)	117	—
5.Head, ears, eyes, nose, throat, neck (week 52)	3	—
5.Head, ears, eyes, nose, throat, neck (week 52)	7	—
6. Lymph node palpation (week -2)	131	—
6. Lymph node palpation (week -2)	0	—
6. Lymph node palpation (week -2)	0	—
6. Lymph node palpation (week 26)	128	—
6. Lymph node palpation (week 26)	0	—
6. Lymph node palpation (week 26)	0	—
6. Lymph node palpation (week 52)	127	—
6. Lymph node palpation (week 52)	0	—
6. Lymph node palpation (week 52)	0	—
7. Musculoskeletal system (week -2)	128	—
7. Musculoskeletal system (week -2)	1	—
7. Musculoskeletal system (week -2)	2	—
7. Musculoskeletal system (week 26)	123	—
7. Musculoskeletal system (week 26)	2	—
7. Musculoskeletal system (week 26)	3	—
7. Musculoskeletal system (week 52)	120	—
7. Musculoskeletal system (week 52)	4	—
7. Musculoskeletal system (week 52)	3	—
8) Respiratory system (week -2)	131	—
8) Respiratory system (week -2)	0	—
8) Respiratory system (week -2)	0	—
8) Respiratory system (week 26)	128	—
8) Respiratory system (week 26)	0	—
8) Respiratory system (week 26)	0	—
8) Respiratory system (week 52)	126	—
8) Respiratory system (week 52)	0	—
8) Respiratory system (week 52)	1	—
9) Skin (week -2)	125	—
9) Skin (week -2)	3	—
9) Skin (week -2)	3	—
9) Skin (week 26)	124	—
9) Skin (week 26)	1	—
9) Skin (week 26)	3	—
9) Skin (week 52)	123	—
9) Skin (week 52)	1	—
9) Skin (week 52)	3	—
10) Thyroid gland (week -2)	130	—
10) Thyroid gland (week -2)	0	—
10) Thyroid gland (week -2)	1	—
10) Thyroid gland (week 26)	128	—
10) Thyroid gland (week 26)	0	—
10) Thyroid gland (week 26)	0	—
10) Thyroid gland (week 52)	127	—
10) Thyroid gland (week 52)	0	—
10) Thyroid gland (week 52)	0	—
Oral Semaglutide 7 mg1) Cardiovascular system (week -2)	132	—
1) Cardiovascular system (week -2)	0	—
1) Cardiovascular system (week -2)	0	—
1) Cardiovascular system (week 26)	128	—
1) Cardiovascular system (week 26)	0	—
1) Cardiovascular system (week 26)	0	—
1) Cardiovascular system (week 52)	129	—
1) Cardiovascular system (week 52)	0	—
1) Cardiovascular system (week 52)	0	—
2) Central and peripheral nervous system (week -2)	131	—
2) Central and peripheral nervous system (week -2)	1	—
2) Central and peripheral nervous system (week -2)	0	—
2) Central and peripheral nervous system (week 26)	127	—
2) Central and peripheral nervous system (week 26)	0	—
2) Central and peripheral nervous system (week 26)	1	—
2) Central and peripheral nervous system (week 56)	128	—
2) Central and peripheral nervous system (week 56)	0	—
2) Central and peripheral nervous system (week 56)	1	—
3) Gastrointestinal system, incl. mouth (week -2)	128	—
3) Gastrointestinal system, incl. mouth (week -2)	2	—
3) Gastrointestinal system, incl. mouth (week -2)	2	—
3) Gastrointestinal system, incl. mouth (week 26)	123	—
3) Gastrointestinal system, incl. mouth (week 26)	2	—
3) Gastrointestinal system, incl. mouth (week 26)	3	—
3) Gastrointestinal system, incl. mouth (week 52)	124	—
3) Gastrointestinal system, incl. mouth (week 52)	3	—
3) Gastrointestinal system, incl. mouth (week 52)	2	—
4.General appearance (week -2)	132	—
4.General appearance (week -2)	0	—
4.General appearance (week -2)	0	—
4.General appearance (week 26)	128	—
4.General appearance (week 26)	0	—
4.General appearance (week 26)	0	—
4.General appearance (week 52)	128	—
4.General appearance (week 52)	0	—
4.General appearance (week 52)	1	—
5.Head, ears, eyes, nose, throat, neck (week -2)	127	—
5.Head, ears, eyes, nose, throat, neck (week -2)	2	—
5.Head, ears, eyes, nose, throat, neck (week -2)	3	—
5.Head, ears, eyes, nose, throat, neck (week 26)	122	—
5.Head, ears, eyes, nose, throat, neck (week 26)	1	—
5.Head, ears, eyes, nose, throat, neck (week 26)	5	—
5.Head, ears, eyes, nose, throat, neck (week 52)	123	—
5.Head, ears, eyes, nose, throat, neck (week 52)	1	—
5.Head, ears, eyes, nose, throat, neck (week 52)	5	—
6. Lymph node palpation (week -2)	131	—
6. Lymph node palpation (week -2)	1	—
6. Lymph node palpation (week -2)	0	—
6. Lymph node palpation (week 26)	127	—
6. Lymph node palpation (week 26)	0	—
6. Lymph node palpation (week 26)	1	—
6. Lymph node palpation (week 52)	128	—
6. Lymph node palpation (week 52)	1	—
6. Lymph node palpation (week 52)	0	—
7. Musculoskeletal system (week -2)	126	—
7. Musculoskeletal system (week -2)	3	—
7. Musculoskeletal system (week -2)	3	—
7. Musculoskeletal system (week 26)	123	—
7. Musculoskeletal system (week 26)	2	—
7. Musculoskeletal system (week 26)	3	—
7. Musculoskeletal system (week 52)	125	—
7. Musculoskeletal system (week 52)	1	—
7. Musculoskeletal system (week 52)	3	—
8) Respiratory system (week -2)	132	—
8) Respiratory system (week -2)	0	—
8) Respiratory system (week -2)	0	—
8) Respiratory system (week 26)	127	—
8) Respiratory system (week 26)	0	—
8) Respiratory system (week 26)	1	—
8) Respiratory system (week 52)	127	—
8) Respiratory system (week 52)	1	—
8) Respiratory system (week 52)	1	—
9) Skin (week -2)	127	—
9) Skin (week -2)	0	—
9) Skin (week -2)	5	—
9) Skin (week 26)	127	—
9) Skin (week 26)	0	—
9) Skin (week 26)	1	—
9) Skin (week 52)	127	—
9) Skin (week 52)	1	—
9) Skin (week 52)	1	—
10) Thyroid gland (week -2)	130	—
10) Thyroid gland (week -2)	2	—
10) Thyroid gland (week -2)	0	—
10) Thyroid gland (week 26)	128	—
10) Thyroid gland (week 26)	0	—
10) Thyroid gland (week 26)	0	—
10) Thyroid gland (week 52)	129	—
10) Thyroid gland (week 52)	0	—
10) Thyroid gland (week 52)	0	—
Oral Semaglutide 14 mg1) Cardiovascular system (week -2)	128	—
1) Cardiovascular system (week -2)	0	—
1) Cardiovascular system (week -2)	2	—
1) Cardiovascular system (week 26)	125	—
1) Cardiovascular system (week 26)	1	—
1) Cardiovascular system (week 26)	2	—
1) Cardiovascular system (week 52)	126	—
1) Cardiovascular system (week 52)	0	—
1) Cardiovascular system (week 52)	1	—
2) Central and peripheral nervous system (week -2)	130	—
2) Central and peripheral nervous system (week -2)	0	—
2) Central and peripheral nervous system (week -2)	0	—
2) Central and peripheral nervous system (week 26)	128	—
2) Central and peripheral nervous system (week 26)	0	—
2) Central and peripheral nervous system (week 26)	0	—
2) Central and peripheral nervous system (week 56)	126	—
2) Central and peripheral nervous system (week 56)	0	—
2) Central and peripheral nervous system (week 56)	1	—
3) Gastrointestinal system, incl. mouth (week -2)	129	—
3) Gastrointestinal system, incl. mouth (week -2)	0	—
3) Gastrointestinal system, incl. mouth (week -2)	1	—
3) Gastrointestinal system, incl. mouth (week 26)	125	—
3) Gastrointestinal system, incl. mouth (week 26)	1	—
3) Gastrointestinal system, incl. mouth (week 26)	2	—
3) Gastrointestinal system, incl. mouth (week 52)	126	—
3) Gastrointestinal system, incl. mouth (week 52)	1	—
3) Gastrointestinal system, incl. mouth (week 52)	0	—
4.General appearance (week -2)	130	—
4.General appearance (week -2)	0	—
4.General appearance (week -2)	0	—
4.General appearance (week 26)	127	—
4.General appearance (week 26)	1	—
4.General appearance (week 26)	0	—
4.General appearance (week 52)	127	—
4.General appearance (week 52)	0	—
4.General appearance (week 52)	0	—
5.Head, ears, eyes, nose, throat, neck (week -2)	124	—
5.Head, ears, eyes, nose, throat, neck (week -2)	2	—
5.Head, ears, eyes, nose, throat, neck (week -2)	4	—
5.Head, ears, eyes, nose, throat, neck (week 26)	125	—
5.Head, ears, eyes, nose, throat, neck (week 26)	1	—
5.Head, ears, eyes, nose, throat, neck (week 26)	2	—
5.Head, ears, eyes, nose, throat, neck (week 52)	122	—
5.Head, ears, eyes, nose, throat, neck (week 52)	2	—
5.Head, ears, eyes, nose, throat, neck (week 52)	3	—
6. Lymph node palpation (week -2)	129	—
6. Lymph node palpation (week -2)	1	—
6. Lymph node palpation (week -2)	0	—
6. Lymph node palpation (week 26)	128	—
6. Lymph node palpation (week 26)	0	—
6. Lymph node palpation (week 26)	0	—
6. Lymph node palpation (week 52)	127	—
6. Lymph node palpation (week 52)	0	—
6. Lymph node palpation (week 52)	0	—
7. Musculoskeletal system (week -2)	127	—
7. Musculoskeletal system (week -2)	2	—
7. Musculoskeletal system (week -2)	1	—
7. Musculoskeletal system (week 26)	124	—
7. Musculoskeletal system (week 26)	2	—
7. Musculoskeletal system (week 26)	2	—
7. Musculoskeletal system (week 52)	123	—
7. Musculoskeletal system (week 52)	2	—
7. Musculoskeletal system (week 52)	2	—
8) Respiratory system (week -2)	130	—
8) Respiratory system (week -2)	0	—
8) Respiratory system (week -2)	0	—
8) Respiratory system (week 26)	128	—
8) Respiratory system (week 26)	0	—
8) Respiratory system (week 26)	0	—
8) Respiratory system (week 52)	127	—
8) Respiratory system (week 52)	0	—
8) Respiratory system (week 52)	0	—
9) Skin (week -2)	128	—
9) Skin (week -2)	1	—
9) Skin (week -2)	1	—
9) Skin (week 26)	126	—
9) Skin (week 26)	1	—
9) Skin (week 26)	1	—
9) Skin (week 52)	125	—
9) Skin (week 52)	1	—
9) Skin (week 52)	1	—
10) Thyroid gland (week -2)	129	—
10) Thyroid gland (week -2)	0	—
10) Thyroid gland (week -2)	1	—
10) Thyroid gland (week 26)	128	—
10) Thyroid gland (week 26)	0	—
10) Thyroid gland (week 26)	0	—
10) Thyroid gland (week 52)	127	—
10) Thyroid gland (week 52)	0	—
10) Thyroid gland (week 52)	0	—
Dulaglutide 0.75 mg1) Cardiovascular system (week -2)	60	—
1) Cardiovascular system (week -2)	1	—
1) Cardiovascular system (week -2)	4	—
1) Cardiovascular system (week 26)	59	—
1) Cardiovascular system (week 26)	1	—
1) Cardiovascular system (week 26)	4	—
1) Cardiovascular system (week 52)	58	—
1) Cardiovascular system (week 52)	1	—
1) Cardiovascular system (week 52)	4	—
2) Central and peripheral nervous system (week -2)	64	—
2) Central and peripheral nervous system (week -2)	0	—
2) Central and peripheral nervous system (week -2)	1	—
2) Central and peripheral nervous system (week 26)	62	—
2) Central and peripheral nervous system (week 26)	0	—
2) Central and peripheral nervous system (week 26)	2	—
2) Central and peripheral nervous system (week 56)	62	—
2) Central and peripheral nervous system (week 56)	0	—
2) Central and peripheral nervous system (week 56)	1	—
3) Gastrointestinal system, incl. mouth (week -2)	60	—
3) Gastrointestinal system, incl. mouth (week -2)	0	—
3) Gastrointestinal system, incl. mouth (week -2)	5	—
3) Gastrointestinal system, incl. mouth (week 26)	60	—
3) Gastrointestinal system, incl. mouth (week 26)	0	—
3) Gastrointestinal system, incl. mouth (week 26)	4	—
3) Gastrointestinal system, incl. mouth (week 52)	59	—
3) Gastrointestinal system, incl. mouth (week 52)	0	—
3) Gastrointestinal system, incl. mouth (week 52)	4	—
4.General appearance (week -2)	64	—
4.General appearance (week -2)	1	—
4.General appearance (week -2)	0	—
4.General appearance (week 26)	62	—
4.General appearance (week 26)	1	—
4.General appearance (week 26)	1	—
4.General appearance (week 52)	62	—
4.General appearance (week 52)	1	—
4.General appearance (week 52)	0	—
5.Head, ears, eyes, nose, throat, neck (week -2)	55	—
5.Head, ears, eyes, nose, throat, neck (week -2)	4	—
5.Head, ears, eyes, nose, throat, neck (week -2)	6	—
5.Head, ears, eyes, nose, throat, neck (week 26)	56	—
5.Head, ears, eyes, nose, throat, neck (week 26)	3	—
5.Head, ears, eyes, nose, throat, neck (week 26)	5	—
5.Head, ears, eyes, nose, throat, neck (week 52)	53	—
5.Head, ears, eyes, nose, throat, neck (week 52)	4	—
5.Head, ears, eyes, nose, throat, neck (week 52)	6	—
6. Lymph node palpation (week -2)	65	—
6. Lymph node palpation (week -2)	0	—
6. Lymph node palpation (week -2)	0	—
6. Lymph node palpation (week 26)	64	—
6. Lymph node palpation (week 26)	0	—
6. Lymph node palpation (week 26)	0	—
6. Lymph node palpation (week 52)	63	—
6. Lymph node palpation (week 52)	0	—
6. Lymph node palpation (week 52)	0	—
7. Musculoskeletal system (week -2)	64	—
7. Musculoskeletal system (week -2)	0	—
7. Musculoskeletal system (week -2)	1	—
7. Musculoskeletal system (week 26)	61	—
7. Musculoskeletal system (week 26)	0	—
7. Musculoskeletal system (week 26)	3	—
7. Musculoskeletal system (week 52)	62	—
7. Musculoskeletal system (week 52)	0	—
7. Musculoskeletal system (week 52)	1	—
8) Respiratory system (week -2)	64	—
8) Respiratory system (week -2)	0	—
8) Respiratory system (week -2)	1	—
8) Respiratory system (week 26)	62	—
8) Respiratory system (week 26)	0	—
8) Respiratory system (week 26)	2	—
8) Respiratory system (week 52)	62	—
8) Respiratory system (week 52)	0	—
8) Respiratory system (week 52)	1	—
9) Skin (week -2)	63	—
9) Skin (week -2)	0	—
9) Skin (week -2)	2	—
9) Skin (week 26)	62	—
9) Skin (week 26)	1	—
9) Skin (week 26)	1	—
9) Skin (week 52)	61	—
9) Skin (week 52)	0	—
9) Skin (week 52)	2	—
10) Thyroid gland (week -2)	64	—
10) Thyroid gland (week -2)	0	—
10) Thyroid gland (week -2)	1	—
10) Thyroid gland (week 26)	63	—
10) Thyroid gland (week 26)	0	—
10) Thyroid gland (week 26)	1	—
10) Thyroid gland (week 52)	62	—
10) Thyroid gland (week 52)	0	—
10) Thyroid gland (week 52)	1	—

Secondary/registry result

Number of Treatment-emergent Severe or Blood Glucose-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	4	—
Oral Semaglutide 7 mg	4	—
Oral Semaglutide 14 mg	4	—
Dulaglutide 0.75 mg	0	—

Secondary/registry result

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

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 3 mg	3	—
Oral Semaglutide 7 mg	3	—
Oral Semaglutide 14 mg	4	—
Dulaglutide 0.75 mg	0	—

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, event

Secondary/protocol endpoint

Change in Physical Examination

Time frame:Week -2, week 26, week 52

descriptive

Secondary/protocol endpoint

Number of Treatment-emergent Severe or Blood Glucose-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

Other clinical outcomes

2 endpoints

Secondary/registry result

Change in Eye Examination Category

Time frame:Week -2, week 52

categorical status, descriptive

Posted result

Group	Value (count_of_participants), Participants	95% CI
Oral Semaglutide 3 mgLeft eye (week -2)	96	—
Left eye (week -2)	7	—
Left eye (week -2)	28	—
Left eye (week 52)	90	—
Left eye (week 52)	10	—
Left eye (week 52)	26	—
Right eye (week -2)	94	—
Right eye (week -2)	6	—
Right eye (week -2)	31	—
Right eye (week 52)	93	—
Right eye (week 52)	9	—
Right eye (week 52)	24	—
Oral Semaglutide 7 mgLeft eye (week -2)	97	—
Left eye (week -2)	2	—
Left eye (week -2)	33	—
Left eye (week 52)	92	—
Left eye (week 52)	8	—
Left eye (week 52)	29	—
Right eye (week -2)	98	—
Right eye (week -2)	3	—
Right eye (week -2)	31	—
Right eye (week 52)	90	—
Right eye (week 52)	8	—
Right eye (week 52)	31	—
Oral Semaglutide 14 mgLeft eye (week -2)	90	—
Left eye (week -2)	2	—
Left eye (week -2)	38	—
Left eye (week 52)	93	—
Left eye (week 52)	3	—
Left eye (week 52)	31	—
Right eye (week -2)	89	—
Right eye (week -2)	2	—
Right eye (week -2)	39	—
Right eye (week 52)	90	—
Right eye (week 52)	6	—
Right eye (week 52)	31	—
Dulaglutide 0.75 mgLeft eye (week -2)	48	—
Left eye (week -2)	4	—
Left eye (week -2)	13	—
Left eye (week 52)	46	—
Left eye (week 52)	3	—
Left eye (week 52)	14	—
Right eye (week -2)	44	—
Right eye (week -2)	6	—
Right eye (week -2)	15	—
Right eye (week 52)	48	—
Right eye (week 52)	4	—
Right eye (week 52)	11	—

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

Effect of Orally Administered Semaglutide Versus Dulaglutide on Diabetes-Related Quality of Life in Japanese Patients with Type 2 Diabetes: The PIONEER 10 Randomized, Active-Controlled Trial.
Diabetes therapy : research, treatment and education of diabetes and related disorders2021 Feb (month)PMID33460016doi:10.1007/s13300-020-00985-wvia CT.gov reference + 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
Safety and efficacy of oral semaglutide versus dulaglutide in Japanese patients with type 2 diabetes (PIONEER 10): an open-label, randomised, active-controlled, phase 3a trial.
The lancet. Diabetes & endocrinology2020 May (month)PMID32333876doi:10.1016/S2213-8587(20)30074-7via CT.gov reference + 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

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.