A Research Study on How Well Semaglutide Works in Adolescents With Overweight or Obesity

• ClinicalTrials.gov Identifier: NCT04102189
• Recruitment Status: Completed
• First Posted: September 25, 2019
• Results First Posted: April 18, 2023
• Last Update Posted: April 18, 2023
• Sponsor: Novo Nordisk A/S
• Information provided by (Responsible Party): Novo Nordisk A/S

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Conditions: Overweight; Obesity
• Interventions: Drug: Semaglutide; Other: Placebo
• Enrollment: 201

Participant Flow

Recruitment Details	The trial was conducted at 37 sites in 8 countries, as follows: Austria (3), Belgium (4), Croatia (3), Ireland (1), Mexico (1), Russia (7), Great Britain (6), United States (12).
Pre-assignment Details	Participants were randomized 2:1 to receive either semaglutide subcutaneously (s.c.) once weekly or semaglutide placebo s.c. once weekly for a dose escalation period of 16 weeks and a maintenance period of 52 weeks. This was followed by a 7-week follow-up period after 'end of treatment' due to the long half-life of semaglutide.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once weekly s.c. injection of semaglutide for 68 weeks. Participants initially received 0.25 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants received once weekly s.c. injection of placebo matched to semaglutide for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Period Title: Overall Study
Started	134	67
Treated	133	67
Full Analysis Set (FAS)	134	67
Safety Analysis Set	133	67
Completed	132	64
Not Completed	2	3
Reason Not Completed
Withdrawal by Subject	1	2
Withdrawal by parent/guardian	0	1
Lost to Follow-up	1	0

Baseline Characteristics

Arm/Group Title		Semaglutide 2.4 mg	Placebo	Total
Arm/Group Description		Participants received once weekly s.c. injection of semaglutide for 68 weeks. Participants initially received 0.25 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants received once weekly s.c. injection of placebo matched to semaglutide for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Total of all reporting groups
Overall Number of Baseline Participants		134	67	201
Baseline Analysis Population Description		The full analysis set (FAS) included all randomized participants according to the intention-to-treat principle.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	134 participants	67 participants	201 participants
		15.5 (1.5)	15.3 (1.6)	15.4 (1.6)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	134 participants	67 participants	201 participants
	Female	84 62.7%	41 61.2%	125 62.2%
	Male	50 37.3%	26 38.8%	76 37.8%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	134 participants	67 participants	201 participants
	Hispanic or Latino	14 10.4%	8 11.9%	22 10.9%
	Not Hispanic or Latino	120 89.6%	59 88.1%	179 89.1%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
Race	Number Analyzed	134 participants	67 participants	201 participants
	White	104 77.6%	55 82.1%	159 79.1%
	Other	14 10.4%	6 9.0%	20 10.0%
	Black or African American	11 8.2%	5 7.5%	16 8.0%
	Asian	3 2.2%	1 1.5%	4 2.0%
	American Indian or Alaska Native	2 1.5%	0 0.0%	2 1.0%

Outcome Measures

1. Primary Outcome

Title	Change in Body Mass Index (BMI) (Percentage [%])
Description	Change in BMI (%) from baseline to week 68 is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site.
Time Frame	Baseline (week 0), week 68

Outcome Measure Data

Analysis Population Description

The full analysis set (FAS) included all randomized participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = number of participants evaluable for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once weekly s.c. injection of semaglutide for 68 weeks. Participants initially received 0.25 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants received once weekly s.c. injection of placebo matched to semaglutide for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	131	62
Mean (Standard Deviation); Unit of Measure: Percentage change of BMI
	-16.2 (12.9)	-0.1 (8.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Semaglutide 2.4 mg, Placebo
	Comments	Responses were analyzed using an analysis of covariance model with randomized treatment, stratification groups (sex and Tanner stage at baseline) and the interaction between stratification groups as factors and baseline BMI as covariate.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<.0001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-16.75
	Confidence Interval	(2-Sided) 95%; -20.27 to -13.23
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Percentage of Participants Achieving Greater Than or Equal to (>=) 5% Reduction of Body Weight (Yes/no)
Description	Percentage of participants who achieved >= 5% weight reduction from baseline (week 0) to week 68 is presented. In the reported data, 'Yes' infers the percentage of participants who have achieved >= 5% weight reduction, whereas 'No' infers the percentage of participants who did not achieve >= 5% weight reduction. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to last contact with trial site.
Time Frame	At week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = number of participants evaluable for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once weekly s.c. injection of semaglutide for 68 weeks. Participants initially received 0.25 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants received once weekly s.c. injection of placebo matched to semaglutide for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	131	62
Measure Type: Number; Unit of Measure: Percentage of participants
Yes	72.5	17.7
No	27.5	82.3

3. Secondary Outcome

Title	Change in Body Weight (Kilograms [kg])
Description	Change in body weight (kg) from baseline to week 68 is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site.
Time Frame	Baseline (week 0), week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = number of participants evaluable for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once weekly s.c. injection of semaglutide for 68 weeks. Participants initially received 0.25 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants received once weekly s.c. injection of placebo matched to semaglutide for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	131	62
Mean (Standard Deviation); Unit of Measure: kg
	-15.7 (14.6)	2.3 (9.7)

4. Secondary Outcome

Title	Change in Body Weight (%)
Description	Change in body weight (%) from baseline to week 68 is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site.
Time Frame	Baseline (week 0), week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = number of participants evaluable for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once weekly s.c. injection of semaglutide for 68 weeks. Participants initially received 0.25 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants received once weekly s.c. injection of placebo matched to semaglutide for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	131	62
Mean (Standard Deviation); Unit of Measure: Percentage change of body weight
	-14.8 (13.2)	2.3 (9.1)

5. Secondary Outcome

Title	Percentage of Participants Achieving >=10% Reduction of Body Weight (Yes/no)
Description	Percentage of participants who achieved >= 10% weight reduction from baseline (week 0) to week 68 is presented. In the reported data, 'Yes' infers the percentage of participants who have achieved >= 10% weight reduction, whereas 'No' infers the percentage of participants who did not achieve >= 10% weight reduction. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to last contact with trial site.
Time Frame	At week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = number of participants evaluable for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once weekly s.c. injection of semaglutide for 68 weeks. Participants initially received 0.25 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants received once weekly s.c. injection of placebo matched to semaglutide for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	131	62
Measure Type: Number; Unit of Measure: Percentage of participants
Yes	61.8	8.1
No	38.2	91.9

6. Secondary Outcome

Title	Percentage of Participants Achieving >=15% Reduction of Body Weight (Yes/no)
Description	Percentage of participants who achieved >= 15% weight reduction from baseline (week 0) to week 68 is presented. In the reported data, 'Yes' infers the percentage of participants who have achieved >= 15% weight reduction, whereas 'No' infers the percentage of participants who did not achieve >= 15% weight reduction. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to last contact with trial site.
Time Frame	At week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = number of participants evaluable for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once weekly s.c. injection of semaglutide for 68 weeks. Participants initially received 0.25 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants received once weekly s.c. injection of placebo matched to semaglutide for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	131	62
Measure Type: Number; Unit of Measure: Percentage of participants
Yes	53.4	4.8
No	46.6	95.2

7. Secondary Outcome

Title	Percentage of Participants Achieving >=20% Reduction of Body Weight (Yes/no)
Description	Percentage of participants who achieved >= 20% weight reduction from baseline (week 0) to week 68 is presented. In the reported data, 'Yes' infers the percentage of participants who have achieved >= 20% weight reduction, whereas 'No' infers the percentage of participants who did not achieve >= 20% weight reduction. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to last contact with trial site.
Time Frame	At week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = number of participants evaluable for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once weekly s.c. injection of semaglutide for 68 weeks. Participants initially received 0.25 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants received once weekly s.c. injection of placebo matched to semaglutide for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	131	62
Measure Type: Number; Unit of Measure: Percentage of participants
Yes	37.4	3.2
No	62.6	96.8

8. Secondary Outcome

Title	Change in BMI Percentage of the 95th Percentile on Gender and Age-specific Growth Charts (CDC.Gov [CDC: {Centers for Disease Control and Prevention}])
Description	Change from baseline in BMI percentage of the 95th percentile on gender and age-specific growth charts (CDC.gov) at week 68 is presented. CDC gender and age-specific growth charts: normal (BMI less than [<] 85th percentile), overweight (BMI greater than or equal to [>=] 85th - <95th percentile), obesity class I (BMI >=95th - <120% of the 95th percentile), obesity class II (BMI >=120% of the 95th percentile - <140% of the 95th percentile) and obesity class III (BMI >=140% of the 95th percentile). Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site.
Time Frame	Baseline (week 0), week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = number of participants evaluable for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once weekly s.c. injection of semaglutide for 68 weeks. Participants initially received 0.25 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants received once weekly s.c. injection of placebo matched to semaglutide for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	131	62
Mean (Standard Deviation); Unit of Measure: Percentage point of BMI
	-24.9 (17.0)	-4.5 (10.5)

9. Secondary Outcome

Title	Percentage of Participants Achieving Improvement in Weight Category (Yes/no)
Description	Percentage of participants who achieved improvement in weight category from baseline (week 0) to week 68 is presented. Improvement in weight category was defined as being in a lower weight category at week 68 compared to baseline according to CDC gender and age-specific growth charts: normal (BMI <85th percentile), overweight (BMI >=85th - <95th percentile), obesity class I (BMI >=95th - <120% of the 95th percentile), obesity class II (BMI >=120% of the 95th percentile - <140% of the 95th percentile) and obesity class III (BMI >=140% of the 95th percentile). In the reported data, 'Yes' infers the percentage of participants who have achieved improvement in weight category, whereas 'No' infers the percentage of participants who did not achieve improvement in weight category. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site.
Time Frame	At week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = number of participants evaluable for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once weekly s.c. injection of semaglutide for 68 weeks. Participants initially received 0.25 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants received once weekly s.c. injection of placebo matched to semaglutide for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	131	62
Measure Type: Number; Unit of Measure: Percentage of participants
Yes	71.8	21.0
No	28.2	79.0

10. Secondary Outcome

Title	Change in BMI (Standard Deviation Score [SDS])
Description	Change in BMI SDS from baseline to week 68 is presented. The SDS scores are also called as z-scores. BMI SDS was calculated using the following formula: Z=[(value /M)^L - 1] / S*L; where L, M and S are median (M), skewness (L) and variation coefficient (S) of children/adolescents' BMI provided for each sex and age. For each subject, a standard deviation score Z (SDS) was calculated based on age and sex referring to the values L, M and S. The method is described in the world health organisation (WHO) Multicentre Growth Reference, which also contains the values for L, M and S by age and sex. For Z (SDS) scores below -3 and above 3, the score was adjusted as described in the WHO instruction. Possible values range from -3 to +3, a negative score being beneficial. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site.
Time Frame	Baseline (week 0), week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = number of participants evaluable for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once weekly s.c. injection of semaglutide for 68 weeks. Participants initially received 0.25 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants received once weekly s.c. injection of placebo matched to semaglutide for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	131	62
Mean (Standard Deviation); Unit of Measure: standard deviation score
	-1.1 (0.9)	-0.1 (0.5)

11. Secondary Outcome

Title	Change in BMI (Kilograms Per Meter Square [kg/m^2])
Description	Change in BMI (kg/m^2) from baseline to week 68 is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site.
Time Frame	Baseline (week 0), week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = number of participants evaluable for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once weekly s.c. injection of semaglutide for 68 weeks. Participants initially received 0.25 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants received once weekly s.c. injection of placebo matched to semaglutide for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	131	62
Mean (Standard Deviation); Unit of Measure: kg/m^2
	-5.9 (4.9)	0.0 (3.1)

12. Secondary Outcome

Title	Change in Waist Circumference
Description	Change in waist circumference (centimeters [cm]) from baseline to week 68 is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site.
Time Frame	Baseline (week 0), week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = number of participants evaluable for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once weekly s.c. injection of semaglutide for 68 weeks. Participants initially received 0.25 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants received once weekly s.c. injection of placebo matched to semaglutide for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	131	62
Mean (Standard Deviation); Unit of Measure: cm
	-12.7 (12.2)	-0.5 (6.5)

13. Secondary Outcome

Title	Percentage of Participants Achieving >=5% Reduction of BMI (Yes/no)
Description	Percentage of participants who achieved >= 5% reduction of BMI from baseline (week 0) to week 68 is presented. In the reported data, 'Yes' infers the percentage of participants who have achieved >= 5% BMI reduction, whereas 'No' infers the percentage of participants who did not achieve >= 5% BMI reduction. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to last contact with trial site.
Time Frame	At week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = number of participants evaluable for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once weekly s.c. injection of semaglutide for 68 weeks. Participants initially received 0.25 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants received once weekly s.c. injection of placebo matched to semaglutide for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	131	62
Measure Type: Number; Unit of Measure: Percentage of participants
Yes	75.6	22.6
No	24.4	77.4

14. Secondary Outcome

Title	Change in Systolic Blood Pressure
Description	Change in systolic blood pressure from baseline to week 68 is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site.
Time Frame	Baseline (week 0), week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = number of participants evaluable for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once weekly s.c. injection of semaglutide for 68 weeks. Participants initially received 0.25 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants received once weekly s.c. injection of placebo matched to semaglutide for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	131	62
Mean (Standard Deviation); Unit of Measure: millimeters of mercury (mmHg)
	-3 (12)	-1 (9)

15. Secondary Outcome

Title	Change in Diastolic Blood Pressure
Description	Change in diastolic blood pressure from baseline to week 68 is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site.
Time Frame	Baseline (week 0), week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = number of participants evaluable for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once weekly s.c. injection of semaglutide for 68 weeks. Participants initially received 0.25 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants received once weekly s.c. injection of placebo matched to semaglutide for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	131	62
Mean (Standard Deviation); Unit of Measure: mmHg
	-2 (9)	-1 (8)

16. Secondary Outcome

Title	Change in Glycated Haemoglobin (HbA1c) (%)
Description	Change in HbA1c (%) from baseline to week 68 is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site.
Time Frame	Baseline (week 0), week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = number of participants evaluable for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once weekly s.c. injection of semaglutide for 68 weeks. Participants initially received 0.25 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants received once weekly s.c. injection of placebo matched to semaglutide for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	126	59
Mean (Standard Deviation); Unit of Measure: Percentage of HbA1c
	-0.4 (0.3)	-0.1 (0.3)

17. Secondary Outcome

Title	Change in HbA1c (Millimoles Per Mole [mmol/Mol])
Description	Change in HbA1c (mmol/mol) from baseline to week 68 is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site.
Time Frame	Baseline (week 0), week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = number of participants evaluable for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once weekly s.c. injection of semaglutide for 68 weeks. Participants initially received 0.25 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants received once weekly s.c. injection of placebo matched to semaglutide for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	126	59
Mean (Standard Deviation); Unit of Measure: mmol/mol
	-4.2 (3.5)	-1.2 (2.9)

18. Secondary Outcome

Title	Change in Fasting Plasma Glucose (Millimoles Per Liter [mmol/L])
Description	Change in fasting plasma glucose (mmol/L) from baseline to week 68 is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site.
Time Frame	Baseline (week 0), week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = number of participants evaluable for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once weekly s.c. injection of semaglutide for 68 weeks. Participants initially received 0.25 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants received once weekly s.c. injection of placebo matched to semaglutide for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	127	57
Mean (Standard Deviation); Unit of Measure: mmol/L
	-0.2 (0.5)	0.0 (0.5)

19. Secondary Outcome

Title	Change in Fasting Plasma Glucose (Milligrams Per Deciliter [mg/dL])
Description	Change in fasting plasma glucose (mg/dL) from baseline to week 68 is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site.
Time Frame	Baseline (week 0), week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = number of participants evaluable for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once weekly s.c. injection of semaglutide for 68 weeks. Participants initially received 0.25 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants received once weekly s.c. injection of placebo matched to semaglutide for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	127	57
Mean (Standard Deviation); Unit of Measure: mg/dL
	-4.2 (9.6)	0.0 (8.6)

20. Secondary Outcome

Title	Change in Fasting Insulin (Picomoles Per Liter [Pmol/L]): Ratio to Baseline
Description	Change in fasting insulin (pmol/L) from baseline to week 68 is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site.
Time Frame	Baseline (week 0), week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = number of participants evaluable for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once weekly s.c. injection of semaglutide for 68 weeks. Participants initially received 0.25 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants received once weekly s.c. injection of placebo matched to semaglutide for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	120	51
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: Ratio of fasting insulin
	0.64; (62.9%)	0.99; (58.2%)

21. Secondary Outcome

Title	Change in Fasting Insulin (Milli International Units Per Milliliter [mIU/mL]): Ratio to Baseline
Description	Change in fasting insulin (mIU/mL) from baseline to week 68 is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site.
Time Frame	Baseline (week 0), week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = number of participants evaluable for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once weekly s.c. injection of semaglutide for 68 weeks. Participants initially received 0.25 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants received once weekly s.c. injection of placebo matched to semaglutide for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	120	51
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: Ratio of fasting insulin
	0.64; (62.9%)	0.99; (58.2%)

22. Secondary Outcome

Title	Change in Total Cholesterol (mmol/L): Ratio to Baseline
Description	Change in total cholesterol (mmol/L) from baseline to week 68 is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site.
Time Frame	Baseline (week 0), week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = number of participants evaluable for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once weekly s.c. injection of semaglutide for 68 weeks. Participants initially received 0.25 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants received once weekly s.c. injection of placebo matched to semaglutide for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	130	58
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: Ratio of total cholesterol
	0.92; (14.6%)	0.98; (9.4%)

23. Secondary Outcome

Title	Change in Total Cholesterol (mg/dL): Ratio to Baseline
Description	Change in total cholesterol (mg/dL) from baseline to week 68 is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site.
Time Frame	Baseline (week 0), week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = number of participants evaluable for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once weekly s.c. injection of semaglutide for 68 weeks. Participants initially received 0.25 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants received once weekly s.c. injection of placebo matched to semaglutide for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	130	58
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: Ratio of total cholesterol
	0.92; (14.6%)	0.98; (9.4%)

24. Secondary Outcome

Title	Change in High-density Lipoprotein (HDL) Cholesterol (mmol/L): Ratio to Baseline
Description	Change in HDL cholesterol (mmol/L) from baseline to week 68 is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site.
Time Frame	Baseline (week 0), week 68:

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = number of participants evaluable for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once weekly s.c. injection of semaglutide for 68 weeks. Participants initially received 0.25 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants received once weekly s.c. injection of placebo matched to semaglutide for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	124	57
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: Ratio of HDL cholesterol
	1.08; (17.5%)	1.03; (21.5%)

25. Secondary Outcome

Title	Change in High-density Lipoprotein (HDL) Cholesterol (mg/dL): Ratio to Baseline
Description	Change in HDL cholesterol (mg/dL) from baseline to week 68 is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site.
Time Frame	Baseline (week 0), week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = number of participants evaluable for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once weekly s.c. injection of semaglutide for 68 weeks. Participants initially received 0.25 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants received once weekly s.c. injection of placebo matched to semaglutide for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	124	57
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: Ratio of HDL cholesterol
	1.08; (17.5%)	1.03; (21.5%)

26. Secondary Outcome

Title	Change in Low-density Lipoprotein (LDL) Cholesterol (mmol/L): Ratio to Baseline
Description	Change in LDL cholesterol (mmol/L) from baseline to week 68 is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site.
Time Frame	Baseline (week 0), week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = number of participants evaluable for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once weekly s.c. injection of semaglutide for 68 weeks. Participants initially received 0.25 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants received once weekly s.c. injection of placebo matched to semaglutide for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	129	58
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: Ratio of LDL cholesterol
	0.91; (20.9%)	0.96; (15.4%)

27. Secondary Outcome

Title	Change in LDL Cholesterol (mg/dL): Ratio to Baseline
Description	Change in LDL cholesterol (mg/dL) from baseline to week 68 is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site.
Time Frame	Baseline (week 0), week 68:

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = number of participants evaluable for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once weekly s.c. injection of semaglutide for 68 weeks. Participants initially received 0.25 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants received once weekly s.c. injection of placebo matched to semaglutide for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	129	58
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: Ratio of LDL cholesterol
	0.91; (20.9%)	0.96; (15.4%)

28. Secondary Outcome

Title	Change in Very Low-density Lipoprotein (VLDL) Cholesterol (mmol/L): Ratio to Baseline
Description	Change in VLDL cholesterol (mmol/L) from baseline to week 68 is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site.
Time Frame	Baseline (week 0), week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = number of participants evaluable for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once weekly s.c. injection of semaglutide for 68 weeks. Participants initially received 0.25 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants received once weekly s.c. injection of placebo matched to semaglutide for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	129	58
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: Ratio of VLDL cholesterol
	0.71; (46.1%)	1.03; (40.8%)

29. Secondary Outcome

Title	Change in VLDL Cholesterol (mg/dL): Ratio to Baseline
Description	Change in VLDL cholesterol (mg/dL) from baseline to week 68 is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site.
Time Frame	Baseline (week 0), week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = number of participants evaluable for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once weekly s.c. injection of semaglutide for 68 weeks. Participants initially received 0.25 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants received once weekly s.c. injection of placebo matched to semaglutide for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	129	58
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: Ratio of VLDL cholesterol
	0.71; (46.1%)	1.03; (40.8%)

30. Secondary Outcome

Title	Change in Triglycerides (mmol/L): Ratio to Baseline
Description	Change in triglycerides (mmol/L) from baseline to week 68 is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site.
Time Frame	Baseline (week 0), week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = number of participants evaluable for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once weekly s.c. injection of semaglutide for 68 weeks. Participants initially received 0.25 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants received once weekly s.c. injection of placebo matched to semaglutide for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	129	58
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: Ratio of triglycerides
	0.71; (45.8%)	1.04; (40.9%)

31. Secondary Outcome

Title	Change in Triglycerides (mg/dL): Ratio to Baseline
Description	Change in triglycerides (mg/dL) from baseline to week 68 is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site.
Time Frame	Baseline (week 0), week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = number of participants evaluable for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once weekly s.c. injection of semaglutide for 68 weeks. Participants initially received 0.25 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants received once weekly s.c. injection of placebo matched to semaglutide for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	129	58
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: Ratio of triglycerides
	0.71; (45.8%)	1.04; (40.9%)

32. Secondary Outcome

Title	Change in Alanine Aminotransferase (ALT): Ratio to Baseline
Description	Change in ALT (units per liter [U/L]) from baseline to week 68 is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from randomization to last contact with trial site.
Time Frame	Baseline (week 0), week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = number of participants evaluable for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once weekly s.c. injection of semaglutide for 68 weeks. Participants initially received 0.25 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants received once weekly s.c. injection of placebo matched to semaglutide for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	128	58
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: Ratio of ALT
	0.79; (63.8%)	1.00; (44.3%)

33. Secondary Outcome

Title	Number of Treatment-emergent Adverse Events (TEAEs)
Description	An adverse event (AE) was any untoward medical occurrence in a clinical trial participant administered or using a medicinal product, whether or not considered related to the medicinal product or usage. All AEs reported here are TEAEs. TEAE is defined as an event that had onset date during the on-treatment period. The on-treatment period was defined as the interval from first to last trial product administration plus 7 weeks of follow-up and excluding any period of temporary treatment interruption defined as greater than (>) 7 consecutive missed doses (corresponding to >7 weeks off-treatment).
Time Frame	From baseline (week 0) to week 75

Outcome Measure Data

Analysis Population Description

The safety analysis set (SAS) included all randomized participants exposed to at least one dose of randomized treatment.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once weekly s.c. injection of semaglutide for 68 weeks. Participants initially received 0.25 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants received once weekly s.c. injection of placebo matched to semaglutide for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	133	67
Measure Type: Number; Unit of Measure: Events
	792	328

34. Secondary Outcome

Title	Number of Treatment-emergent Serious Adverse Events (SAEs)
Description	An SAE is an AE that fulfils at least one of the following criteria: 1) results in death; 2) is life-threatening; 3) requires inpatient hospitalisation or prolongation of existing hospitalisation; 4) results in persistent disability/incapacity; 5) is a congenital anomaly/birth defect; 6) important medical event. All AEs reported here are TEAEs. TEAE is defined as an event that had onset date during the on-treatment period. The on-treatment period was defined as the interval from first to last trial product administration plus 7 weeks of follow-up and excluding any period of temporary treatment interruption defined as >7 consecutive missed doses (corresponding to >7 weeks off-treatment).
Time Frame	From baseline (week 0) to week 75

Outcome Measure Data

Analysis Population Description

SAS included all randomized participants exposed to at least one dose of randomized treatment.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once weekly s.c. injection of semaglutide for 68 weeks. Participants initially received 0.25 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants received once weekly s.c. injection of placebo matched to semaglutide for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	133	67
Measure Type: Number; Unit of Measure: Events
	17	7

35. Secondary Outcome

Title	Change in Pulse
Description	Change in pulse from baseline to week 68 is presented. Data is reported for on-treatment period: the on-treatment period was defined as the interval from first to last trial product administration plus 2 weeks of follow-up and excluding any period of temporary treatment interruption defined as >2 consecutive missed doses (corresponding to >2 weeks off-treatment).
Time Frame	Baseline (week 0), week 68

Outcome Measure Data

Analysis Population Description

SAS included all randomized participants exposed to at least one dose of randomized treatment. Overall Number of Participants Analyzed = number of participants evaluable for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once weekly s.c. injection of semaglutide for 68 weeks. Participants initially received 0.25 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants received once weekly s.c. injection of placebo matched to semaglutide for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	119	58
Mean (Standard Deviation); Unit of Measure: Beats per minute (beats/min)
	0 (13)	-1 (13)

36. Secondary Outcome

Title	Change in Amylase: Ratio to Baseline
Description	Change in amylase (U/L) from baseline to week 68 is presented as ratio to baseline. Data is reported for on-treatment period: the on-treatment period was defined as the interval from first to last trial product administration plus 2 weeks of follow-up and excluding any period of temporary treatment interruption defined as >2 consecutive missed doses (corresponding to >2 weeks off-treatment).
Time Frame	Baseline (week 0), week 68

Outcome Measure Data

Analysis Population Description

SAS included all randomized participants exposed to at least one dose of randomized treatment.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once weekly s.c. injection of semaglutide for 68 weeks. Participants initially received 0.25 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants received once weekly s.c. injection of placebo matched to semaglutide for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	133	67
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: Ratio of amylase
	1.15; (17.4%)	1.04; (18.2%)

37. Secondary Outcome

Title	Change in Lipase: Ratio to Baseline
Description	Change in lipase (U/L) from baseline to week 68 is presented as ratio to baseline. Data is reported for on-treatment period: the on-treatment period was defined as the interval from first to last trial product administration plus 2 weeks of follow-up and excluding any period of temporary treatment interruption defined as >2 consecutive missed doses (corresponding to >2 weeks off-treatment).
Time Frame	Baseline (week 0), week 68

Outcome Measure Data

Analysis Population Description

SAS included all randomized participants exposed to at least one dose of randomized treatment.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once weekly s.c. injection of semaglutide for 68 weeks. Participants initially received 0.25 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants received once weekly s.c. injection of placebo matched to semaglutide for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	133	67
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: Ratio of lipase
	1.39; (37.3%)	1.12; (37.0%)

38. Secondary Outcome

Title	Change in Calcitonin: Ratio to Baseline
Description	Change in calcitonin (nanograms per liter [ng/L]) from baseline to week 68 is presented as ratio to baseline. Data is reported for on-treatment period: the on-treatment period was defined as the interval from first to last trial product administration plus 2 weeks of follow-up and excluding any period of temporary treatment interruption defined as >2 consecutive missed doses (corresponding to >2 weeks off-treatment).
Time Frame	Baseline (week 0), week 68

Outcome Measure Data

Analysis Population Description

SAS included all randomized participants exposed to at least one dose of randomized treatment. Overall Number of Participants Analyzed = number of participants evaluable for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once weekly s.c. injection of semaglutide for 68 weeks. Participants initially received 0.25 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants received once weekly s.c. injection of placebo matched to semaglutide for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	116	55
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: Ratio of calcitonin
	1.14; (47.0%)	1.09; (36.7%)

Adverse Events

Time Frame	From baseline (week 0) to week 75
Adverse Event Reporting Description	All AEs reported here are TEAEs. TEAE is defined as an event that had onset date during the on-treatment period. The on-treatment period was defined as the interval from first to last trial product administration plus 7 weeks of follow-up and excluding any period of temporary treatment interruption defined as >7 consecutive missed doses (corresponding to >7 weeks off-treatment). SAS included all randomized participants exposed to at least one dose of randomized treatment.
Arm/Group Title	Semaglutide 2.4 mg		Placebo
Arm/Group Description	Participants received once weekly s.c. injection of semaglutide for 68 weeks. Participants initially received 0.25 mg of semaglutide and the dose was then escalated once in 4 weeks for 16 weeks until the target dose of 2.4 mg was reached which was maintained for a period of 52 weeks: 0.25 mg (week 1 to week 4), 0.5 mg (week 5 to week 8), 1.0 mg (week 9 to week 12), 1.7 mg (week 13 to week 16) and 2.4 mg (week 17 to week 68). The treatment was an adjunct to a reduced-calorie diet and increased physical activity.		Participants received once weekly s.c. injection of placebo matched to semaglutide for 68 weeks. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
All-Cause Mortality
	Semaglutide 2.4 mg		Placebo
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/133 (0.00%)		0/67 (0.00%)
Serious Adverse Events
	Semaglutide 2.4 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/133 (11.28%)		6/67 (8.96%)
Gastrointestinal disorders
Abdominal pain † 1	1/133 (0.75%)	1	0/67 (0.00%)	0
Abdominal pain upper † 1	0/133 (0.00%)	0	1/67 (1.49%)	1
Gastritis † 1	1/133 (0.75%)	1	0/67 (0.00%)	0
Vomiting † 1	1/133 (0.75%)	1	0/67 (0.00%)	0
Hepatobiliary disorders
Cholecystitis acute † 1	1/133 (0.75%)	1	0/67 (0.00%)	0
Cholelithiasis † 1	3/133 (2.26%)	3	0/67 (0.00%)	0
Hepatic function abnormal † 1	1/133 (0.75%)	1	0/67 (0.00%)	0
Infections and infestations
Appendicitis † 1	2/133 (1.50%)	2	0/67 (0.00%)	0
COVID-19 † 1	1/133 (0.75%)	1	0/67 (0.00%)	0
COVID-19 pneumonia † 1	1/133 (0.75%)	1	0/67 (0.00%)	0
Injury, poisoning and procedural complications
Clavicle fracture † 1	0/133 (0.00%)	0	1/67 (1.49%)	1
Contusion † 1	0/133 (0.00%)	0	1/67 (1.49%)	1
Post procedural constipation † 1	1/133 (0.75%)	1	0/67 (0.00%)	0
Urinary retention postoperative † 1	1/133 (0.75%)	1	0/67 (0.00%)	0
Investigations
Transaminases increased † 1	1/133 (0.75%)	1	1/67 (1.49%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ovarian germ cell teratoma benign † 1	0/133 (0.00%)	0	1/67 (1.49%)	1
Nervous system disorders
Loss of consciousness † 1	0/133 (0.00%)	0	1/67 (1.49%)	1
Tension headache † 1	0/133 (0.00%)	0	1/67 (1.49%)	1
Psychiatric disorders
Depression † 1	1/133 (0.75%)	1	0/67 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Sleep apnoea syndrome † 1	1/133 (0.75%)	1	0/67 (0.00%)	0
1 Term from vocabulary, MedDRA 24; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Semaglutide 2.4 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	90/133 (67.67%)		40/67 (59.70%)
Gastrointestinal disorders
Abdominal pain † 1	20/133 (15.04%)	31	4/67 (5.97%)	4
Abdominal pain upper † 1	11/133 (8.27%)	19	8/67 (11.94%)	11
Constipation † 1	8/133 (6.02%)	8	1/67 (1.49%)	1
Diarrhoea † 1	29/133 (21.80%)	54	13/67 (19.40%)	19
Nausea † 1	56/133 (42.11%)	127	12/67 (17.91%)	29
Vomiting † 1	48/133 (36.09%)	105	7/67 (10.45%)	18
General disorders
Fatigue † 1	4/133 (3.01%)	4	5/67 (7.46%)	5
Pyrexia † 1	5/133 (3.76%)	5	5/67 (7.46%)	5
Infections and infestations
COVID-19 † 1	15/133 (11.28%)	16	10/67 (14.93%)	10
Gastroenteritis † 1	9/133 (6.77%)	9	2/67 (2.99%)	2
Nasopharyngitis † 1	16/133 (12.03%)	21	7/67 (10.45%)	12
Injury, poisoning and procedural complications
Contusion † 1	2/133 (1.50%)	2	4/67 (5.97%)	4
Investigations
Blood creatine phosphokinase increased † 1	1/133 (0.75%)	1	4/67 (5.97%)	4
Metabolism and nutrition disorders
Decreased appetite † 1	8/133 (6.02%)	8	3/67 (4.48%)	4
Nervous system disorders
Dizziness † 1	10/133 (7.52%)	13	2/67 (2.99%)	3
Headache † 1	22/133 (16.54%)	52	11/67 (16.42%)	20
Reproductive system and breast disorders
Dysmenorrhoea † 1	2/133 (1.50%)	3	4/67 (5.97%)	7
Respiratory, thoracic and mediastinal disorders
Cough † 1	4/133 (3.01%)	5	4/67 (5.97%)	4
Skin and subcutaneous tissue disorders
Acne † 1	4/133 (3.01%)	4	4/67 (5.97%)	4
1 Term from vocabulary, MedDRA 24; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

At the end of the trial, one or more scientific publications may be prepared collaboratively by the investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for up to 60 days to protect intellectual property.

Results Point of Contact

• Name/Title: Clinical Reporting Office (2834)
• Organization: Novo Nordisk A/S
• Phone: (+1) 866-867-7178
• EMail: clinicaltrials@novonordisk.com

Publications of Results:

Weghuber D, Barrett T, Barrientos-Perez M, Gies I, Hesse D, Jeppesen OK, Kelly AS, Mastrandrea LD, Sorrig R, Arslanian S; STEP TEENS Investigators. Once-Weekly Semaglutide in Adolescents with Obesity. N Engl J Med. 2022 Dec 15;387(24):2245-2257. doi: 10.1056/NEJMoa2208601. Epub 2022 Nov 2.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Cuda S, Censani M. Progress in pediatric obesity: new and advanced therapies. Curr Opin Pediatr. 2022 Aug 1;34(4):407-413. doi: 10.1097/MOP.0000000000001150. Epub 2022 Jul 5.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT04102189
• Other Study ID Numbers: NN9536-4451; U1111-1215-7560 ( Other Identifier: World Health Organization (WHO) ); 2018-002431-18 ( EudraCT Number )
• First Submitted: September 23, 2019
• First Posted: September 25, 2019
• Results First Submitted: March 24, 2023
• Results First Posted: April 18, 2023
• Last Update Posted: April 18, 2023