Phase 3 · Semaglutide

PIONEER TEENS trial results

Efficacy and Safety of Oral Semaglutide Versus Placebo Both in Combination With Metformin and/or Basal Insulin in Children and Adolescents With Type 2 Diabetes

Change From Baseline (Week 0) to Week 26 in Glycosylated Haemoglobin (HbA1c)- Percentage Point (Percentage point), Baseline (Week 0), Week 26. Oral Semaglutide: -1.0; Placebo: -0.3.

Participants: 132
Status: completed
Completed: 2026-02-03
Sponsor: Novo Nordisk A/S

As posted on ClinicalTrials.gov (NCT04596631), updated at source Aug 21, 2026. Read again whenever the registry updates it. Registry figures can differ from a published paper, which may use another analysis.

Primary outcome

What PIONEER TEENS measured first

Change From Baseline (Week 0) to Week 26 in Glycosylated Haemoglobin (HbA1c)- Percentage PointPercentage point · Baseline (Week 0), Week 26 · mean

Oral Semaglutiden=66	Placebon=62
-1.0(1.5)	-0.3(1.3)

Change From Baseline (Week 0) in HbA1c to Week 26- Millimoles Per Mole (mmol/Mol)mmol/mol · Baseline (Week 0), Week 26 · mean

Oral Semaglutiden=66	Placebon=62
-11.2(16.5)	-2.8(14.3)

Side effects by arm

Side effects in PIONEER TEENS

Percent of participants affected, From Baseline (Week 0) up to 57 weeks. The most common events the registry lists.

Event	Oral Semaglutide	Placebo
Any serious event	7.6%	3%
Nausea	25.8%	13.6%
Diarrhoea	22.7%	16.7%
Vomiting	19.7%	12.1%
Headache	15.2%	18.2%
Cough	13.6%	1.5%
Nasopharyngitis	12.1%	10.6%
Oropharyngeal pain	12.1%	4.5%
Upper respiratory tract infection	12.1%	9.1%
Pyrexia	10.6%	7.6%
Abdominal pain	9.1%	9.1%
COVID-19	9.1%	6.1%
Glycosylated haemoglobin increased	9.1%	7.6%
Abdominal pain upper	7.6%	6.1%
Gastroenteritis	1.5%	7.6%
Rhinitis	7.6%	1.5%
Decreased appetite	3%	6.1%
Dizziness	6.1%	3%
Pharyngitis streptococcal	6.1%	0%

Secondary outcomes

What else it measured

Change From Baseline (Week 0) in Fasting Plasma Glucose (FPG) to Week 26mg/dL · Baseline (Week 0), Week 26 · mean

Oral Semaglutiden=66	Placebon=61
-28.2(49.1)	-8.1(65.1)

Change From Baseline (Week 0) in Body Mass Index (BMI) Standard Deviation Score (SDS) to Week 26standard deviation score · Baseline (Week 0), Week 26 · mean

Oral Semaglutiden=66	Placebon=65
-0.1(0.3)	-0.1(0.3)

Change From Baseline in HbA1c at Week 52 (Percentage Point)Percentage point · Baseline (Week 0), Week 52 · mean

Oral Semaglutiden=62	Placebon=64
-0.8(1.4)	0.2(1.4)

Change From Baseline in HbA1c at Week 52 (mmol/Mol)mmol/mol · Baseline (Week 0), Week 52 · mean

Oral Semaglutiden=62	Placebon=64
-9.0(15.8)	2.5(14.8)

Change From Baseline in Fasting Plasma Glucose at Week 52 (mg/dL)mg/dL · Baseline (Week 0), Week 52 · mean

Oral Semaglutiden=59	Placebon=63
-21.2(54.8)	2.2(53.8)

Change From Baseline in Body Weight to Week 26 and Week 52 (Kilograms [kg])kg · Baseline (Week 0), Week 26, Week 52 · mean

Measure	Oral Semaglutiden=66	Placebon=65
Week 26	-1.3(4.1)	-0.4(5.7)
Week 52	-0.7(5.1)	1.1(5.8)

Relative Change From Baseline in Body Weight to Week 26 and Week 52Percent change in body weight · Baseline (Week 0), Week 26, Week 52 · mean

Measure	Oral Semaglutiden=66	Placebon=65
Week 26	-1.55(5.18)	0.18(4.85)
Week 52	-0.94(6.57)	1.86(5.54)

Change From Baseline in Waist Circumference to Week 26 and Week 52cm · Baseline (Week 0), Week 26, Week 52 · mean

Measure	Oral Semaglutiden=66	Placebon=64
Week 26	-1.6(5.7)	-1.6(5.4)
Week 52	-2.0(5.9)	-0.4(6.3)

Change From Baseline in Body Mass Index Standard Deviation Score at Week 52Standard deviation score · Baseline (Week 0), Week 52 · mean

Oral Semaglutiden=64	Placebon=65
-0.2(0.4)	-0.0(0.3)

Change From Baseline (Week 0) in BMI Percentile (Age and Gender Adjusted) to Week 26 and Week 52Percentile of BMI · Baseline (Week 0), Week 26, Week 52 · mean

Measure	Oral Semaglutiden=66	Placebon=65
Week 26	-1.7(7.6)	0.2(1.9)
Week 52	-2.9(10.4)	0.5(3.3)

Change From Baseline in Body Mass Index at Week 26 and Week 52kg/m^2 · Baseline (Week 0), Week 26, Week 52 · mean

Measure	Oral Semaglutiden=66	Placebon=65
Week 26	-0.8(1.6)	-0.5(2.1)
Week 52	-0.7(2.0)	-0.1(2.1)

Percent Change From Baseline in Body Mass Index at Week 26 and Week 52Percent Change · Baseline (Week 0), Week 26, Week 52 · mean

Measure	Oral Semaglutiden=66	Placebon=65
Week 26	-2.49(5.34)	-1.00(4.92)
Week 52	-2.47(6.85)	0.13(5.59)

The trial

How PIONEER TEENS was run

This study compares 2 medicines for type 2 diabetes: semaglutide (new medicine) and a dummy medicine (placebo). Semaglutide will be tested to see how well it works compared to the dummy medicine. The study will also test if semaglutide is safe in children and teenagers. Participants will either get semaglutide or the dummy medicine - which one is decided by chance. Participants will take 1 tablet of the study medicine every morning on an empty stomach. They have to wait 30 minutes before they eat, drink or take any other medication by mouth. The study will last for about 1 year and 3 months (66 weeks). Participants will have 12 clinic visits and 8 phone calls with the study doctor. At all 12 clinic visits, participants will have blood samples taken. Participants will also be asked some questions.

Semaglutide - max. tolerated dose: Participants will receive semaglutide tablets once daily in addition to background treatment with metformin or basal insulin or both, in addition to diet and exercise.
Placebo (semaglutide): Participants will receive semaglutide placebo tablets once daily in addition to background treatment with metformin or basal insulin or both, in addition to diet and exercise.

Who could join the trial

Inclusion Criteria: * Informed consent from parent(s) or legally acceptable representative (LAR) and child assent from the subject 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, aged 10 to below 18 years at the day of randomisation * HbA1c 6.5%-11.0% (47-97 mmol/mol) (both inclusive) * Diagnosed with type 2 diabetes mellitus according to the American Diabetes Association criteria and treated with: * stable metformin dose (stable metformin dose is defined as at least 1000 mg daily or the maximum tolerated dose for 56 days or longer prior to screening) or * stable metformin dose and a stable dose of basal insulin (stable dose of basal insulin is defined as basal insulin treatment equal to or more than 30 days prior to screening, compared to the dose at screening, dose adjustments of ± 25% are allowed) or * stable dose of basal insulin Exclusion Criteria: * Diagnosis of type 1 diabetes * Maturity onset diabetes of the young (MODY) * Positive insulinoma associated-protein 2 (IA-2) antibodies or anti-glutamic acid decarboxylase (anti-GAD) antibodies.

Trial averages do not predict what one person will experience. Results are shown as the registry posts them, without interpretation.

GLPcompare is an informational data platform, not a medical provider or pharmacy. Nothing here is medical advice, a diagnosis, or a recommendation to start, stop, or change any treatment. Data is aggregated from public sources and can be incomplete or out of date. Always confirm with a licensed clinician and the current FDA label.