← Trials/Trial dossier/NCT04707469

PIONEER PLUS

CompletedPhase 3Results posted

Research Study to Compare Three Doses of Semaglutide Tablets Taken Once Daily in People With Type 2 Diabetes

Efficacy and Safety of Once-daily Oral Semaglutide 25 mg and 50 mg Compared With 14 mg in Subjects With Type 2 Diabetes

Lead sponsor

Novo Nordisk A/S

Asset

Semaglutide

Oral · GLP-1 agonist

Listed sites

228

Recruiting sites

—

Enrollment

1,606

actual

Study population

Type 2 diabetes

Key I/E criteria

•BMI ≥25•HbA1c 8-10.5%

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 IDNCT04707469

Org study IDNN9924-4635

Secondary ID2020-000299-39European Medicines Agency (EudraCT)

Secondary IDU1111-1247-0210World Health Organization (WHO)

Timeline

Milestones

Study first posted2021-01-13actual

Study start2021-01-15actual

Primary completion2023-03-07actual

Study completion2023-03-08actual

Results first posted2024-04-03actual

Last update posted2025-12-09actual

Assets

Investigational agents

Semaglutide

Study populations

Who this study enrolls

Type 2 diabetes

Eligibility

Who can enroll

Minimum age18 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Male or female, age above or equal to 18 years at the time of signing informed consent.

•Diagnosed with type 2 diabetes mellitus at least 180 days prior to the day of screening.

•HbA1c of 8.0-10.5% (64-91 mmol/mol) (both inclusive).

•BMI equal to or above 25 kg/m^2

•Stable daily dose(s) for 90 days prior to the day of screening of any of the following treatment regimens:

•No more than 3 of the following oral anti-diabetic drugs and at least 1 marked with a *:

–Metformin (equal to or above1500 mg or maximum tolerated or effective dose).

–Sulfonylureas (SU) (equal to or above half of the maximum approved dose according to local label or maximum tolerated or effective dose).

–Sodium/glucose cotransporter 2 (SGLT2) inhibitors (maximum tolerated dose).

•Dipeptidyl peptidase-4 (DPP-4) inhibitors (maximally indicated dose as per local label).

•Subjects, on treatment with stable dose of DPP-4 inhibitors at inclusion, must be willing to discontinue DPP-4 inhibitor treatment at randomisation (with no wash-out).

Exclusion criteria

•Treatment with any medication indicated for the treatment of diabetes or obesity other than stated in the inclusion criteria within the past 90 days prior to the day of screening. However, short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed.

•Renal impairment measured as estimated glomerular filtration rate (eGFR) value of below 30 mL/min/1.73 m^2 according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation as defined by kidney disease improving global outcomes (KDIGO 2012) classification.

•Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days prior to screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.

Endpoints (78)

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

Cardiometabolic biomarkers

Weight & body composition

Glycemic / diabetes

Safety / tolerability / PK

Weight & body composition

26 endpoints

Secondary/registry result

Change From Baseline in Body Weight (Week 52)

Time frame:Baseline (week 0), week 52

Body weight, absolute change (kg)

change from baseline, improvement

Posted result

Group	Value (mean), Kilogram (Kg)	95% CI
Oral Semaglutide 14 mg	-4.4	—
Oral Semaglutide 25 mg	-7.1	—
Oral Semaglutide 50 mg	-8.3	—

Secondary/registry result

Change From Baseline in Body Weight (Week 68)

Time frame:Baseline (week 0), week 68

Body weight, absolute change (kg)

change from baseline, improvement

Posted result

Group	Value (mean), Kg	95% CI
Oral Semaglutide 14 mg	-4.5	—
Oral Semaglutide 25 mg	-7.1	—
Oral Semaglutide 50 mg	-8.2	—

Secondary/registry result

Percentage Change From Baseline in Body Weight (Week 52)

Time frame:Baseline (week 0), week 52

Body weight, % change

percent change from baseline, improvement

Posted result

Group	Value (mean), Percentage change in body weight	95% CI
Oral Semaglutide 14 mg	-4.7	—
Oral Semaglutide 25 mg	-7.3	—
Oral Semaglutide 50 mg	-8.5	—

Secondary/registry result

Percentage Change From Baseline in Body Weight (Week 68)

Time frame:Baseline (week 0), week 68

Body weight, % change

percent change from baseline, improvement

Posted result

Group	Value (mean), Percentage change in body weight	95% CI
Oral Semaglutide 14 mg	-4.7	—
Oral Semaglutide 25 mg	-7.2	—
Oral Semaglutide 50 mg	-8.4	—

Secondary/registry result

Percentage Change From Week 12 in Body Weight (Week 52)

Time frame:Week 12, Week 52

Body weight, % change

percent change from baseline, improvement

Posted result

Group	Value (mean), Percentage change in body weight	95% CI
Oral Semaglutide 14 mg	-1.5	—
Oral Semaglutide 25 mg	-3.8	—
Oral Semaglutide 50 mg	-5.4	—

Secondary/registry result

Change From Baseline in Body Mass Index (BMI) (Week 52)

Time frame:Baseline (week 0), week 52

BMI, change

change from baseline, improvement

Posted result

Group	Value (mean), kilogram per square metre (kg/m^2)	95% CI
Oral Semaglutide 14 mg	-1.6	—
Oral Semaglutide 25 mg	-2.5	—
Oral Semaglutide 50 mg	-2.9	—

Secondary/registry result

Change From Baseline in BMI (Week 68)

Time frame:Baseline (week 0), week 68

BMI, change

change from baseline, improvement

Posted result

Group	Value (mean), kg/m^2	95% CI
Oral Semaglutide 14 mg	-1.6	—
Oral Semaglutide 25 mg	-2.5	—
Oral Semaglutide 50 mg	-2.9	—

Secondary/registry result

Change From Baseline in Waist Circumference (Week 52)

Time frame:Baseline (week 0), week 52

Waist circumference, change

change from baseline, improvement

Posted result

Group	Value (mean), centimetre (cm)	95% CI
Oral Semaglutide 14 mg	-4	—
Oral Semaglutide 25 mg	-5	—
Oral Semaglutide 50 mg	-6	—

Secondary/registry result

Change From Baseline in Waist Circumference (Week 68)

Time frame:Baseline (week 0), week 68

Waist circumference, change

change from baseline, improvement

Posted result

Group	Value (mean), cm	95% CI
Oral Semaglutide 14 mg	-4	—
Oral Semaglutide 25 mg	-6	—
Oral Semaglutide 50 mg	-7	—

Secondary/registry result

Percentage of Participants Who Achieved Weight Loss Greater Than or Equal to (>=) 5 % (Week 52)

Time frame:At week 52

≥5% weight-loss responders

threshold achievement, improvement

Posted result

Group	Value (number), Percentage of participants	95% CI
Oral Semaglutide 14 mg	41	—
Oral Semaglutide 25 mg	60	—
Oral Semaglutide 50 mg	67.5	—

Secondary/registry result

Percentage of Participants Who Achieved Weight Loss >= 5 % (Week 68)

Time frame:At week 68

≥5% weight-loss responders

threshold achievement, improvement

Posted result

Group	Value (number), Percentage of participants	95% CI
Oral Semaglutide 14 mg	42.2	—
Oral Semaglutide 25 mg	58.5	—
Oral Semaglutide 50 mg	65.7	—

Secondary/registry result

Percentage of Participants Who Achieved Weight Loss >= 10 % (Week 52)

Time frame:At week 52

≥10% weight-loss responders

threshold achievement, improvement

Posted result

Group	Value (number), Percentage of participants	95% CI
Oral Semaglutide 14 mg	13.9	—
Oral Semaglutide 25 mg	29	—
Oral Semaglutide 50 mg	37.2	—

Secondary/registry result

Percentage of Participants Who Achieved Weight Loss >= 10 % (Week 68)

Time frame:At week 68

≥10% weight-loss responders

threshold achievement, improvement

Posted result

Group	Value (number), Percentage of participants	95% CI
Oral Semaglutide 14 mg	14.3	—
Oral Semaglutide 25 mg	29.4	—
Oral Semaglutide 50 mg	34.7	—

Secondary/protocol endpoint

Change From Baseline in Body Weight (Week 52)

Time frame:Baseline (week 0), week 52

Body weight, absolute change (kg)

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in Body Weight (Week 68)

Time frame:Baseline (week 0), week 68

Body weight, absolute change (kg)

change from baseline, improvement

Secondary/protocol endpoint

Percentage Change From Baseline in Body Weight (Week 52)

Time frame:Baseline (week 0), week 52

Body weight, % change

percent change from baseline, improvement

Secondary/protocol endpoint

Percentage Change From Baseline in Body Weight (Week 68)

Time frame:Baseline (week 0), week 68

Body weight, % change

percent change from baseline, improvement

Secondary/protocol endpoint

Percentage Change From Week 12 in Body Weight (Week 52)

Time frame:Week 12, Week 52

Body weight, % change

percent change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in Body Mass Index (BMI) (Week 52)

Time frame:Baseline (week 0), week 52

BMI, change

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in BMI (Week 68)

Time frame:Baseline (week 0), week 68

BMI, change

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in Waist Circumference (Week 52)

Time frame:Baseline (week 0), week 52

Waist circumference, change

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in Waist Circumference (Week 68)

Time frame:Baseline (week 0), week 68

Waist circumference, change

change from baseline, improvement

Secondary/protocol endpoint

Percentage of Participants Who Achieved Weight Loss Greater Than or Equal to (>=) 5 % (Week 52)

Time frame:At week 52

≥5% weight-loss responders

threshold achievement, improvement

Secondary/protocol endpoint

Percentage of Participants Who Achieved Weight Loss >= 5 % (Week 68)

Time frame:At week 68

≥5% weight-loss responders

threshold achievement, improvement

Secondary/protocol endpoint

Percentage of Participants Who Achieved Weight Loss >= 10 % (Week 52)

Time frame:At week 52

≥10% weight-loss responders

threshold achievement, improvement

Secondary/protocol endpoint

Percentage of Participants Who Achieved Weight Loss >= 10 % (Week 68)

Time frame:At week 68

≥10% weight-loss responders

threshold achievement, improvement

Glycemic / diabetes

20 endpoints

Primary/registry result

Change From Baseline in Glycated Haemoglobin (HbA1c) (Week 52)

Time frame:Baseline (week 0), week 52

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Posted result

Group	Value (mean), Percentage point of HbA1c	95% CI
Oral Semaglutide 14 mg	-1.5	—
Oral Semaglutide 25 mg	-1.9	—
Oral Semaglutide 50 mg	-2.1	—

Treatment difference-0.2795% CI-0.42 – -0.12p0.0006ANCOVA

Treatment policy estimand

Treatment difference-0.5395% CI-0.68 – -0.38p<.0001ANCOVA

Treatment policy estimand

Primary/protocol endpoint

Change From Baseline in Glycated Haemoglobin (HbA1c) (Week 52)

Time frame:Baseline (week 0), week 52

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Secondary/registry result

Change From Baseline in HbA1c (Week 68)

Time frame:Baseline (week 0), week 68

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Posted result

Group	Value (mean), Percentage point of HbA1c	95% CI
Oral Semaglutide 14 mg	-1.5	—
Oral Semaglutide 25 mg	-1.8	—
Oral Semaglutide 50 mg	-2.0	—

Secondary/registry result

Change From Week 12 in HbA1c (Week 52)

Time frame:Week 12, Week 52

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Posted result

Group	Value (mean), Percentage point of HbA1c	95% CI
Oral Semaglutide 14 mg	-0.4	—
Oral Semaglutide 25 mg	-0.8	—
Oral Semaglutide 50 mg	-1.0	—

Secondary/registry result

Change From Baseline in Fasting Plasma Glucose (FPG) (Week 52)

Time frame:Baseline (week 0), week 52

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Posted result

Group	Value (mean), millimole per litre (mmol/L)	95% CI
Oral Semaglutide 14 mg	-2.4	—
Oral Semaglutide 25 mg	-3.0	—
Oral Semaglutide 50 mg	-3.2	—

Secondary/registry result

Change From Baseline in FPG (Week 68)

Time frame:Baseline (week 0), week 68

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Posted result

Group	Value (mean), mmol/L	95% CI
Oral Semaglutide 14 mg	-2.4	—
Oral Semaglutide 25 mg	-3.0	—
Oral Semaglutide 50 mg	-3.2	—

Secondary/registry result

Percentage of Participants Who Achieved HbA1c Less Than (<) 7.0 (Percent [%]) (Week 52)

Time frame:At week 52

HbA1c <7.0% achievement

threshold achievement, improvement

LOINC 4548-4

Posted result

Group	Value (number), Percentage of Participants	95% CI
Oral Semaglutide 14 mg	39	—
Oral Semaglutide 25 mg	50.5	—
Oral Semaglutide 50 mg	63	—

Secondary/registry result

Percentage of Participants Who Achieved HbA1c < 7.0 % (Week 68)

Time frame:At week 68

HbA1c <7.0% achievement

threshold achievement, improvement

LOINC 4548-4

Posted result

Group	Value (number), Percentage of Participants	95% CI
Oral Semaglutide 14 mg	39.2	—
Oral Semaglutide 25 mg	49.9	—
Oral Semaglutide 50 mg	58.9	—

Secondary/registry result

Percentage of Participants Who Achieved HbA1c Less Than or Equal to (<=) 6.5 % (Week 52)

Time frame:At week 52

HbA1c <6.5% achievement

threshold achievement, improvement

LOINC 4548-4

Posted result

Group	Value (number), Percentage of Participants	95% CI
Oral Semaglutide 14 mg	25.8	—
Oral Semaglutide 25 mg	39.6	—
Oral Semaglutide 50 mg	51.2	—

Secondary/registry result

Percentage of Participants Who Achieved HbA1c <= 6.5 % (Week 68)

Time frame:At week 68

HbA1c <6.5% achievement

threshold achievement, improvement

LOINC 4548-4

Posted result

Group	Value (number), Percentage of Participants	95% CI
Oral Semaglutide 14 mg	23.6	—
Oral Semaglutide 25 mg	35.8	—
Oral Semaglutide 50 mg	46.2	—

Secondary/registry result

Time to Event Analyses of Rescue Medication

Time frame:Baseline (week 0), week 68

time to event, event

Posted result

Group	Value (median), Weeks	95% CI
Oral Semaglutide 14 mg	NA	NA – NA
Oral Semaglutide 25 mg	NA	NA – NA
Oral Semaglutide 50 mg	NA	NA – NA

Secondary/protocol endpoint

Change From Baseline in HbA1c (Week 68)

Time frame:Baseline (week 0), week 68

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Secondary/protocol endpoint

Change From Week 12 in HbA1c (Week 52)

Time frame:Week 12, Week 52

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Secondary/protocol endpoint

Change From Baseline in Fasting Plasma Glucose (FPG) (Week 52)

Time frame:Baseline (week 0), week 52

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Secondary/protocol endpoint

Change From Baseline in FPG (Week 68)

Time frame:Baseline (week 0), week 68

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Secondary/protocol endpoint

Percentage of Participants Who Achieved HbA1c Less Than (<) 7.0 (Percent [%]) (Week 52)

Time frame:At week 52

HbA1c <7.0% achievement

threshold achievement, improvement

LOINC 4548-4

Secondary/protocol endpoint

Percentage of Participants Who Achieved HbA1c < 7.0 % (Week 68)

Time frame:At week 68

HbA1c <7.0% achievement

threshold achievement, improvement

LOINC 4548-4

Secondary/protocol endpoint

Percentage of Participants Who Achieved HbA1c Less Than or Equal to (<=) 6.5 % (Week 52)

Time frame:At week 52

HbA1c <6.5% achievement

threshold achievement, improvement

LOINC 4548-4

Secondary/protocol endpoint

Percentage of Participants Who Achieved HbA1c <= 6.5 % (Week 68)

Time frame:At week 68

HbA1c <6.5% achievement

threshold achievement, improvement

LOINC 4548-4

Secondary/protocol endpoint

Time to Event Analyses of Rescue Medication

Time frame:Baseline (week 0), week 68

time to event, event

Cardiometabolic biomarkers

28 endpoints

Secondary/registry result

Change From Baseline in Total Cholesterol (Week 52)

Time frame:Baseline, Week 52

Total cholesterol, change

change from baseline, improvement

LOINC 2093-3

Posted result

Group	Value (mean), mmol/L	95% CI
Oral Semaglutide 14 mg	-0.04	—
Oral Semaglutide 25 mg	-0.15	—
Oral Semaglutide 50 mg	-0.06	—

Secondary/registry result

Change From Baseline in Total Cholesterol (Week 68)

Time frame:Baseline, Week 68

Total cholesterol, change

change from baseline, improvement

LOINC 2093-3

Posted result

Group	Value (mean), mmol/L	95% CI
Oral Semaglutide 14 mg	-0.03	—
Oral Semaglutide 25 mg	-0.08	—
Oral Semaglutide 50 mg	-0.06	—

Secondary/registry result

Change From Baseline in Low Density Lipoproteins (LDL) (Week 52)

Time frame:Baseline, Week 52

LDL-C, change

change from baseline, improvement

LOINC 13457-7

Posted result

Group	Value (mean), mmol/L	95% CI
Oral Semaglutide 14 mg	0.04	—
Oral Semaglutide 25 mg	-0.01	—
Oral Semaglutide 50 mg	0.11	—

Secondary/registry result

Change From Baseline in LDL (Week 68)

Time frame:Baseline, Week 68

LDL-C, change

change from baseline, improvement

LOINC 13457-7

Posted result

Group	Value (mean), mmol/L	95% CI
Oral Semaglutide 14 mg	0.07	—
Oral Semaglutide 25 mg	0.06	—
Oral Semaglutide 50 mg	0.08	—

Secondary/registry result

Change From Baseline in High Density Lipoproteins (HDL) (Week 52)

Time frame:Baseline, Week 52

HDL-C, change

change from baseline, improvement

LOINC 2085-9

Posted result

Group	Value (mean), mmol/L	95% CI
Oral Semaglutide 14 mg	0.06	—
Oral Semaglutide 25 mg	0.07	—
Oral Semaglutide 50 mg	0.08	—

Secondary/registry result

Change From Baseline in HDL (Week 68)

Time frame:Baseline, Week 68

HDL-C, change

change from baseline, improvement

LOINC 2085-9

Posted result

Group	Value (mean), mmol/L	95% CI
Oral Semaglutide 14 mg	0.06	—
Oral Semaglutide 25 mg	0.08	—
Oral Semaglutide 50 mg	0.09	—

Secondary/registry result

Change From Baseline in Triglycerides (Week 52)

Time frame:Baseline, Week 52

Triglycerides, change

change from baseline, improvement

LOINC 2571-8

Posted result

Group	Value (mean), mmol/L	95% CI
Oral Semaglutide 14 mg	-0.46	—
Oral Semaglutide 25 mg	-0.65	—
Oral Semaglutide 50 mg	-0.71	—

Secondary/registry result

Change From Baseline in Triglycerides (Week 68)

Time frame:Baseline, Week 68

Triglycerides, change

change from baseline, improvement

LOINC 2571-8

Posted result

Group	Value (mean), mmol/L	95% CI
Oral Semaglutide 14 mg	-0.51	—
Oral Semaglutide 25 mg	-0.65	—
Oral Semaglutide 50 mg	-0.70	—

Secondary/registry result

Change From Baseline in Systolic Blood Pressure (Week 52)

Time frame:Baseline (week 0), week 52

Systolic BP, change

change from baseline, improvement

LOINC 8480-6

Posted result

Group	Value (mean), millimetres of mercury (mmHg)	95% CI
Oral Semaglutide 14 mg	-4	—
Oral Semaglutide 25 mg	-6	—
Oral Semaglutide 50 mg	-6	—

Secondary/registry result

Change From Baseline in Systolic Blood Pressure (Week 68)

Time frame:Baseline (week 0), week 68

Systolic BP, change

change from baseline, improvement

LOINC 8480-6

Posted result

Group	Value (mean), mmHg	95% CI
Oral Semaglutide 14 mg	-4	—
Oral Semaglutide 25 mg	-6	—
Oral Semaglutide 50 mg	-5	—

Secondary/registry result

Change From Baseline in Diastolic Blood Pressure (Week 52)

Time frame:Baseline (week 0), week 52

Diastolic BP, change

change from baseline, improvement

LOINC 8462-4

Posted result

Group	Value (mean), mmHg	95% CI
Oral Semaglutide 14 mg	-2	—
Oral Semaglutide 25 mg	-2	—
Oral Semaglutide 50 mg	-2	—

Secondary/registry result

Change From Baseline in Diastolic Blood Pressure (Week 68)

Time frame:Baseline (week 0), week 68

Diastolic BP, change

change from baseline, improvement

LOINC 8462-4

Posted result

Group	Value (mean), mmHg	95% CI
Oral Semaglutide 14 mg	-3	—
Oral Semaglutide 25 mg	-3	—
Oral Semaglutide 50 mg	-2	—

Secondary/registry result

Change From Baseline in Pulse (Week 52)

Time frame:Baseline (week 0), week 52

Heart rate, change

change from baseline, improvement

Posted result

Group	Value (mean), beats per minute (beats/min)	95% CI
Oral Semaglutide 14 mg	2	—
Oral Semaglutide 25 mg	2	—
Oral Semaglutide 50 mg	3	—

Secondary/registry result

Change From Baseline in Pulse (Week 68)

Time frame:Baseline (week 0), week 68

Heart rate, change

change from baseline, improvement

Posted result

Group	Value (mean), beats/min	95% CI
Oral Semaglutide 14 mg	1	—
Oral Semaglutide 25 mg	2	—
Oral Semaglutide 50 mg	2	—

Secondary/protocol endpoint

Change From Baseline in Total Cholesterol (Week 52)

Time frame:Baseline, Week 52

Total cholesterol, change

change from baseline, improvement

LOINC 2093-3

Secondary/protocol endpoint

Change From Baseline in Total Cholesterol (Week 68)

Time frame:Baseline, Week 68

Total cholesterol, change

change from baseline, improvement

LOINC 2093-3

Secondary/protocol endpoint

Change From Baseline in Low Density Lipoproteins (LDL) (Week 52)

Time frame:Baseline, Week 52

LDL-C, change

change from baseline, improvement

LOINC 13457-7

Secondary/protocol endpoint

Change From Baseline in LDL (Week 68)

Time frame:Baseline, Week 68

LDL-C, change

change from baseline, improvement

LOINC 13457-7

Secondary/protocol endpoint

Change From Baseline in High Density Lipoproteins (HDL) (Week 52)

Time frame:Baseline, Week 52

HDL-C, change

change from baseline, improvement

LOINC 2085-9

Secondary/protocol endpoint

Change From Baseline in HDL (Week 68)

Time frame:Baseline, Week 68

HDL-C, change

change from baseline, improvement

LOINC 2085-9

Secondary/protocol endpoint

Change From Baseline in Triglycerides (Week 52)

Time frame:Baseline, Week 52

Triglycerides, change

change from baseline, improvement

LOINC 2571-8

Secondary/protocol endpoint

Change From Baseline in Triglycerides (Week 68)

Time frame:Baseline, Week 68

Triglycerides, change

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in Systolic Blood Pressure (Week 52)

Time frame:Baseline (week 0), week 52

Systolic BP, change

change from baseline, improvement

LOINC 8480-6

Secondary/protocol endpoint

Change From Baseline in Systolic Blood Pressure (Week 68)

Time frame:Baseline (week 0), week 68

Systolic BP, change

change from baseline, improvement

LOINC 8480-6

Secondary/protocol endpoint

Change From Baseline in Diastolic Blood Pressure (Week 52)

Time frame:Baseline (week 0), week 52

Diastolic BP, change

change from baseline, improvement

LOINC 8462-4

Secondary/protocol endpoint

Change From Baseline in Diastolic Blood Pressure (Week 68)

Time frame:Baseline (week 0), week 68

Diastolic BP, change

change from baseline, improvement

LOINC 8462-4

Secondary/protocol endpoint

Change From Baseline in Pulse (Week 52)

Time frame:Baseline (week 0), week 52

Heart rate, change

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in Pulse (Week 68)

Time frame:Baseline (week 0), week 68

Heart rate, change

change from baseline, improvement

Safety / tolerability / PK

4 endpoints

Secondary/registry result

Number of Adverse Events

Time frame:From baseline (week 0) up to week 73

Treatment-emergent AEs (any)

event count, event

Posted result

Group	Value (number), Events	95% CI
Oral Semaglutide 14 mg	1641	—
Oral Semaglutide 25 mg	2055	—
Oral Semaglutide 50 mg	2115	—

Secondary/registry result

Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (<3.0 mmol/L (54 Milligram Per Decilitre [mg/dL]) or Severe Hypoglycaemic Episodes (Level 3)

Time frame:From baseline (week 0) up to week 68

Documented hypoglycemia

event count, event

componentsDocumented hypoglycemia, Severe hypoglycemia

Posted result

Group	Value (number), Count of episodes	95% CI
Oral Semaglutide 14 mgLevel 2	65	—
Level 3	0	—
Oral Semaglutide 25 mgLevel 2	44	—
Level 3	0	—
Oral Semaglutide 50 mgLevel 2	35	—
Level 3	1	—

Secondary/protocol endpoint

Number of Adverse Events

Time frame:From baseline (week 0) up to week 73

Treatment-emergent AEs (any)

event count, event

Secondary/protocol endpoint

Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (<3.0 mmol/L (54 Milligram Per Decilitre [mg/dL]) or Severe Hypoglycaemic Episodes (Level 3)

Time frame:From baseline (week 0) up to week 68

Documented hypoglycemia

event count, event

componentsDocumented hypoglycemia, Severe hypoglycemia

Publications (1)

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

Efficacy and safety of once-daily oral semaglutide 25 mg and 50 mg compared with 14 mg in adults with type 2 diabetes (PIONEER PLUS): a multicentre, randomised, phase 3b trial.
Lancet (London, England)2023 Aug 26PMID37385279doi:10.1016/S0140-6736(23)01127-3via 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.