PIONEER START

WithdrawnPhase 3

Research Study to Compare Semaglutide Tablets With Empagliflozin Tablets Taken Once Daily in People With Type 2 Diabetes and Obesity

Efficacy and Safety of Early Initiation of Oral Semaglutide 50 mg Once Daily Versus Empagliflozin 25 mg Once Daily in Younger Patients With Newly Diagnosed Type 2 Diabetes and Obesity

Lead sponsor

Novo Nordisk A/S

Asset

Semaglutide

Oral · GLP-1 agonist

Listed sites

Recruiting sites

—

Enrollment

—

actual

Study population

Obesity / overweight, Type 2 diabetes

Key I/E criterion

•HbA1c 7-9.5%

Primary endpoints

•HbA1c <7.0% achievement•≥5% weight-loss responders

Identifiers

Registered as

NCT IDNCT05444153

Org study IDNN9924-4668

Secondary ID2021-005396-39

Secondary IDU1111-1270-0763World Health Organization (WHO)

Timeline

Milestones

Study first posted2022-07-05actual

Study start2022-10-06estimated

Last update posted2022-11-14actual

Primary completion2024-10-02estimated

Study completion2025-08-29estimated

Assets

Investigational agents

Semaglutide

Study populations

Who this study enrolls

Obesity / overweightType 2 diabetes

Eligibility

Who can enroll

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Male or female, age 18- less than (<) 50 years at the time of signing informed consent.

•Diagnosed with type 2 diabetes mellitus less than or equal to (<=) 365 days from the day of screening.

•Glycated haemoglobin (HbA1c) of 7.0-9.5 percentage (%) (53-80 millimoles per milliliter [mmol/mol]) (both inclusive).

•Body mass index (BMI) greater than or equal to (>=) 30.0 kilograms per meter square (kg/m^2).

•Treatment naïve to any antidiabetic drug(s). However, for a subset of participants (≤25%) any metformin dose or formulations administered is allowed.

Exclusion criteria

•Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria since diagnosed with type 2 diabetes mellitus. Prior insulin treatment for gestational diabetes is allowed.

•Renal impairment measured as estimated glomerular filtration rate (eGFR) value of less than (<) 60 milliliter per minute per 1.73 meter square (1.7mL/min/1.73 m^2) at screening.

•Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days prior to day of 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.

•C-peptide less than (<)1.5 nanograms per milliliter (ng/mL) at screening.

•Positive insulinoma associated-protein 2 (IA-2) antibodies or anti-glutamic acid decarboxylase (anti-GAD) antibodies.

•History of major surgical procedures involving the stomach or small intestine potentially affecting absorption of drugs and/or nutrients.

•Presence of clinically significant gastrointestinal disorders potentially affecting absorption of drugs and/or nutrients, as judged by the investigator.

Endpoints (23)

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

Weight & body composition

Patient-reported / QoL

Safety / tolerability / PK

Weight & body composition

5 endpoints

Primary/protocol endpoint

Participants acheiving body weight reduction greater than or equal to (>=) 5% (Yes/No)

Time frame:At week 104

≥5% weight-loss responders

threshold achievement, improvement

Secondary/protocol endpoint

Change in body weight

Time frame:From randomisation (week 0) to week 104

Body weight, absolute change (kg)

change from baseline, improvement

Secondary/protocol endpoint

Relative change in body weight

Time frame:From randomisation (week 0) to week 104

Body weight, % change

percent change from baseline, improvement

Secondary/protocol endpoint

Change in waist circumference

Time frame:From randomisation (week 0) to week 104

Waist circumference, change

change from baseline, improvement

Secondary/protocol endpoint

Participants achieving body weight reduction greater than or equal to (>=) 5 percentage (%)

Time frame:From randomisation (week 0) to week 104

≥5% weight-loss responders

threshold achievement, improvement

Glycemic / diabetes

8 endpoints

Primary/protocol endpoint

Participants acheiving glycated haemoglobin (HbA1c) less than (<) 7 percentage (%) (Yes/No)

Time frame:At week 104

HbA1c <7.0% achievement

threshold achievement, improvement

LOINC 4548-4

Secondary/protocol endpoint

Change in HbA1c

Time frame:From randomisation (week 0) to week 104

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Secondary/protocol endpoint

Change in fasting plasma glucose (FPG)

Time frame:From randomisation (week 0) to week 104

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Secondary/protocol endpoint

Change in self-measured plasma glucose (SPMG) 7-point mean profile

Time frame:From randomisation (week 0) to week 104

Postprandial glucose

change from baseline, improvement

Secondary/protocol endpoint

Change in self-measured plasma glucose (SPMG) mean post prandial increments

Time frame:From randomisation (week 0) to week 104

Postprandial glucose

change from baseline, improvement

Secondary/protocol endpoint

Time to additional anti-diabetic medication

Time frame:From randomisation (week 0) to week 104

time to event, event

Secondary/protocol endpoint

Participants achieving glycated haemoglobin (HbA1c) less than or equal to (<=) 6.5% (Yes/No)

Time frame:From randomisation (week 0) to week 104

HbA1c <6.5% achievement

threshold achievement, improvement

LOINC 4548-4

Secondary/protocol endpoint

Participants achieving glycated haemoglobin (HbA1c) reduction greater than or equal to (>=) 0.7%-point (Yes/No)

Time frame:From randomisation (week 0) to week 104

threshold achievement, improvement

LOINC 4548-4

Cardiometabolic biomarkers

7 endpoints

Secondary/protocol endpoint

Change in systolic blood pressure

Time frame:From randomisation (week 0) to week 104

Systolic BP, change

change from baseline, improvement

LOINC 8480-6

Secondary/protocol endpoint

Change in total cholesterol

Time frame:From randomisation (week 0) to week 104

Total cholesterol, change

ratio, improvement

LOINC 2093-3

Secondary/protocol endpoint

Change in high density lipoprotein (HDL)

Time frame:From randomisation (week 0) to week 104

HDL-C, change

ratio, improvement

LOINC 2085-9

Secondary/protocol endpoint

Change in low density lipoprotein (LDL)

Time frame:From randomisation (week 0) to week 104

LDL-C, change

ratio, improvement

LOINC 13457-7

Secondary/protocol endpoint

Change in very low density lipoprotein (VLDL)

Time frame:From randomisation (week 0) to week 104

VLDL, change

ratio, improvement

Secondary/protocol endpoint

Change in Triglycerides

Time frame:From randomisation (week 0) to week 104

Triglycerides, change

ratio, improvement

LOINC 2571-8

Secondary/protocol endpoint

Change in free fatty acids

Time frame:From randomisation (week 0) to week 104

Free fatty acids, change

ratio, improvement

Patient-reported / QoL

2 endpoints

Secondary/protocol endpoint

Change in Control of Eating Questionnaire (CoEQ) score - Craving Control domain

Time frame:From randomisation (week 0) to week 104

change from baseline, improvement

Secondary/protocol endpoint

Change in Control of Eating Questionnaire (CoEQ) score - Craving for Savory domaina

Time frame:From randomisation (week 0) to week 104

change from baseline, improvement

Safety / tolerability / PK

1 endpoint

Secondary/protocol endpoint

Number of treatment emergent adverse events

Time frame:From randomisation (week 0) to week 109

Treatment-emergent AEs (any)

event count, event

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 1, 2026

Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)

Results tableno registry results posted yet

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.