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Research Study to Look at How Well Semaglutide is at Lowering Weight When Taken Together With an Intensive Lifestyle Program (STEP 3)

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ClinicalTrials.gov Identifier: NCT03611582
Recruitment Status : Completed
First Posted : August 2, 2018
Results First Posted : July 9, 2021
Last Update Posted : November 11, 2021
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Overweight
Obesity
Interventions Drug: Semaglutide
Drug: Placebo (semaglutide)
Enrollment 611
Recruitment Details The trial was conducted in 41 sites in the United States.
Pre-assignment Details The trial has a 68-week treatment period (16 weeks of dose escalation and 52 weeks of maintenance dose). Participants were randomised in 2:1 ratio either to receive semaglutide 2.4 mg or placebo.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment. Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Period Title: Overall Study
Started 407 204
Full Analysis Set (FAS) 407 204
Safety Analysis Set (SAS) 407 204
Completed 339 166
Not Completed 68 38
Reason Not Completed
Adverse Event             26             6
Protocol Violation             0             1
Pregnancy             1             2
Lack of Efficacy             0             1
At the discretion of the investigator             1             0
Safety concern as judged by the investigator             1             2
Withdrawal by Subject             4             3
Lost to Follow-up             18             7
other             17             16
Arm/Group Title Semaglutide 2.4 mg Placebo Total
Hide Arm/Group Description Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment. Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment. Total of all reporting groups
Overall Number of Baseline Participants 407 204 611
Hide Baseline Analysis Population Description
Full analysis set (FAS) included all randomised participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 407 participants 204 participants 611 participants
46  (13) 46  (13) 46  (13)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 407 participants 204 participants 611 participants
Female
315
  77.4%
180
  88.2%
495
  81.0%
Male
92
  22.6%
24
  11.8%
116
  19.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 407 participants 204 participants 611 participants
Hispanic or Latino
75
  18.4%
46
  22.5%
121
  19.8%
Not Hispanic or Latino
332
  81.6%
158
  77.5%
490
  80.2%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 407 participants 204 participants 611 participants
American Indian or Alaska Native
1
   0.2%
0
   0.0%
1
   0.2%
Asian
5
   1.2%
6
   2.9%
11
   1.8%
Native Hawaiian or Other Pacific Islander
3
   0.7%
0
   0.0%
3
   0.5%
Black or African American
80
  19.7%
36
  17.6%
116
  19.0%
White
307
  75.4%
158
  77.5%
465
  76.1%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
11
   2.7%
4
   2.0%
15
   2.5%
1.Primary Outcome
Title Change in Body Weight (%)
Hide Description Change in body weight from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from both in-trial and on-treatment periods. In-trial observation period: the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact (week 75). On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).
Time Frame Baseline (week 0) to week 68
Hide Outcome Measure Data
Hide Analysis Population Description
Overall number of participants analyzed = full analysis set (FAS) which comprised all randomized participants. Number Analyzed = number of participants with available data.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.
Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Overall Number of Participants Analyzed 407 204
Mean (Standard Deviation)
Unit of Measure: Percentage
In-trial observation period Number Analyzed 373 participants 189 participants
-16.5  (10.1) -5.8  (7.7)
On-treatment observation period Number Analyzed 334 participants 164 participants
-17.6  (9.6) -6.1  (7.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Semaglutide 2.4 mg, Placebo
Comments Treatment policy estimand
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 -10.27
Confidence Interval (2-Sided) 95%
-11.97 to -8.57
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Semaglutide 2.4 mg, Placebo
Comments Hypothetical estimand
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method MMRM (mixed model repeated measurement)
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -12.67
Confidence Interval (2-Sided) 95%
-14.34 to -11.00
Estimation Comments [Not Specified]
2.Primary Outcome
Title Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 5%
Hide Description Number of participants who achieved greater than or equal to (≥) 5% weight loss after 68 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved ≥ 5% weight loss, whereas 'No' infers the number of participants who have not achieved ≥ 5% weight loss. The endpoint was evaluated based on the data from both in-trial and on-treatment observation periods. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75). On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 2 weeks of follow-up. It excludes any period of temporary treatment interruption.
Time Frame After 68 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Overall number of participants analyzed = full analysis set (FAS) which comprised all randomized participants. Number Analyzed = number of participants with available data.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.
Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Overall Number of Participants Analyzed 407 204
Measure Type: Count of Participants
Unit of Measure: Participants
In-trial observation period Number Analyzed 373 participants 189 participants
Yes
323
  86.6%
90
  47.6%
No
50
  13.4%
99
  52.4%
On-treatment observation period Number Analyzed 334 participants 164 participants
Yes
300
  89.8%
82
  50.0%
No
34
  10.2%
82
  50.0%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Semaglutide 2.4 mg, Placebo
Comments Treatment policy estimand
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 6.11
Confidence Interval (2-Sided) 95%
4.04 to 9.26
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Semaglutide 2.4 mg, Placebo
Comments Hypothetical estimand
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method MMRM (mixed model repeated measurement)
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 11.67
Confidence Interval (2-Sided) 95%
7.64 to 17.81
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 10%
Hide Description Number of participants who achieved greater than or equal to (≥) 10% weight loss after 68 weeks is presented. In the reported data, 'Yes' infers number of participants who have achieved ≥ 10% weight loss whereas 'No' infers number of participants who have not achieved ≥ 10% weight loss. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
Time Frame After 68 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomised participants. 'Overall Number of Participants Analyzed' = participants with available data.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.
Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Overall Number of Participants Analyzed 373 189
Measure Type: Count of Participants
Unit of Measure: Participants
Yes
281
  75.3%
51
  27.0%
No
92
  24.7%
138
  73.0%
4.Secondary Outcome
Title Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 15%
Hide Description Number of participants who achieved greater than or equal to (≥) 15% weight loss after 68 weeks is presented. In the reported data, 'Yes' infers number of participants who have achieved ≥ 15% weight loss whereas 'No' infers number of participants who have not achieved ≥ 15% weight loss. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
Time Frame After 68 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomised participants. 'Overall Number of Participants Analyzed' = participants with available data.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.
Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Overall Number of Participants Analyzed 373 189
Measure Type: Count of Participants
Unit of Measure: Participants
Yes
208
  55.8%
25
  13.2%
No
165
  44.2%
164
  86.8%
5.Secondary Outcome
Title Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 20%
Hide Description Number of participants who achieved greater than or equal to (≥) 20% weight loss after 68 weeks is presented. In the reported data, 'Yes' infers number of participants who have achieved ≥ 20% weight loss whereas 'No' infers number of participants who have not achieved ≥ 20% weight loss. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
Time Frame After 68 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomised participants. 'Overall Number of Participants Analyzed' = participants with available data.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.
Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Overall Number of Participants Analyzed 373 189
Measure Type: Count of Participants
Unit of Measure: Participants
Yes
133
  35.7%
7
   3.7%
No
240
  64.3%
182
  96.3%
6.Secondary Outcome
Title Change in Waist Circumference
Hide Description Change in waist circumference from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time Frame Baseline (week 0) to week 68
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomised participants. 'Overall Number of Participants Analyzed' = participants with available data.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.
Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Overall Number of Participants Analyzed 371 189
Mean (Standard Deviation)
Unit of Measure: Centimeter (cm)
-15.2  (10.2) -6.1  (8.6)
7.Secondary Outcome
Title Change in Systolic Blood Pressure
Hide Description Change in systolic blood pressure from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time Frame Baseline (week 0) to week 68
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomised participants. 'Overall Number of Participants Analyzed' = participants with available data.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.
Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Overall Number of Participants Analyzed 372 188
Mean (Standard Deviation)
Unit of Measure: Millimeters of mercury (mmHg)
-6  (14) -2  (15)
8.Secondary Outcome
Title Change in Short Form-36 (SF-36) - Physical Functioning Score
Hide Description SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ questionnaire measured eight domains of functional health and well-being as well as two component summary scores (physical component summary and mental component summary). The 0-100 scale scores from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. In the metric of norm-based scores, 50 and 10 corresponds to the mean and standard deviation respectively. Change from week 0 in the domain scores and component summary scores were evaluated at week 68. A positive change score indicates an improvement since baseline. These endpoints were evaluated based on the data from in-trial observation period which is the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time Frame Baseline (week 0) to week 68
Hide Outcome Measure Data
Hide Analysis Population Description
Overall number of participants analyzed = full analysis set (FAS) which comprised all randomized participants. Number Analyzed = number of participants with available data.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.
Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Overall Number of Participants Analyzed 407 204
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Change in physical functioning score (SF-36) Number Analyzed 364 participants 181 participants
2.5  (5.7) 1.7  (5.7)
Change in SF-36: Role-Physical score Number Analyzed 364 participants 181 participants
1.6  (6.5) 1.5  (6.7)
Change in SF-36: Bodily Pain score Number Analyzed 364 participants 181 participants
1.3  (7.1) 0.6  (8.3)
Change in SF-36: General Health score Number Analyzed 364 participants 181 participants
3.4  (6.6) 1.9  (6.4)
Change in SF-36: Vitality score Number Analyzed 364 participants 181 participants
2.0  (8.2) 0.9  (7.8)
Change in SF-36: Social Functioning score Number Analyzed 364 participants 181 participants
0.1  (6.6) -1.2  (8.0)
Change in SF-36: Mental Health score Number Analyzed 364 participants 181 participants
-0.5  (6.0) -1.5  (7.1)
Change in SF-36: Physical component summary Number Analyzed 364 participants 181 participants
3.2  (6.0) 2.6  (6.5)
Change in SF-36: Mental component summary Number Analyzed 364 participants 181 participants
-0.9  (6.0) -2.2  (8.0)
Change in SF-36: Role-Emotional score Number Analyzed 364 participants 181 participants
-0.6  (5.6) -1.5  (7.7)
9.Secondary Outcome
Title Change in Body Weight (Kg)
Hide Description Change in body weight from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time Frame Baseline (week 0) to week 68
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomised participants. 'Overall Number of Participants Analyzed' = participants with available data.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.
Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Overall Number of Participants Analyzed 373 189
Mean (Standard Deviation)
Unit of Measure: Kilogram (kg)
-17.5  (11.4) -6.2  (8.6)
10.Secondary Outcome
Title Change in Body Mass Index
Hide Description Change in body mass index from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time Frame Baseline (week 0) to week 68
Hide Outcome Measure Data
Hide Analysis Population Description
Overall number of participants analyzed = full analysis set (FAS) which comprised all randomized participants. Number Analyzed = number of participants with available data.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.
Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Overall Number of Participants Analyzed 373 189
Mean (Standard Deviation)
Unit of Measure: Kilogram per square meter (kg/sqm)
-6.2  (4.0) -2.2  (3.1)
11.Secondary Outcome
Title Change in HbA1c (%)
Hide Description Change in glycosylated haemoglobin (HbA1c) from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time Frame Baseline (week 0) to week 68
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomised participants. 'Overall Number of Participants Analyzed' = participants with available data.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.
Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Overall Number of Participants Analyzed 369 184
Mean (Standard Deviation)
Unit of Measure: Percentage point of HbA1c
-0.5  (0.3) -0.3  (0.2)
12.Secondary Outcome
Title Change in HbA1c (mmol/Mol)
Hide Description Change in HbA1c from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time Frame Baseline (week 0) to week 68
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomised participants. 'Overall Number of Participants Analyzed' = participants with available data.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.
Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Overall Number of Participants Analyzed 369 184
Mean (Standard Deviation)
Unit of Measure: mmol/mol
-5.8  (3.1) -3.1  (2.5)
13.Secondary Outcome
Title Change in Fasting Plasma Glucose
Hide Description Change in fasting plasma glucose from week 0 to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time Frame Baseline (week 0) to week 68
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomised participants. 'Overall Number of Participants Analyzed' = participants with available data.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.
Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Overall Number of Participants Analyzed 355 176
Mean (Standard Deviation)
Unit of Measure: milligrams per deciliter (mg/dL)
-7.3  (10.9) -1.1  (10.6)
14.Secondary Outcome
Title Change in Fasting Serum Insulin
Hide Description Change in fasting serum insulin from week 0 to week 68 [measured as milli-international units per milliliter (mIU/mL)] is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time Frame Baseline (week 0) to week 68
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomised participants. 'Overall Number of Participants Analyzed' = participants with available data.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.
Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Overall Number of Participants Analyzed 346 170
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio of fasting serum insulin
0.68
(67.4%)
0.84
(50.6%)
15.Secondary Outcome
Title Change in Diastolic Blood Pressure
Hide Description Change in diastolic blood pressure from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time Frame Baseline (week 0) to week 68
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomised participants. 'Overall Number of Participants Analyzed' = participants with available data.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.
Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Overall Number of Participants Analyzed 372 188
Mean (Standard Deviation)
Unit of Measure: mmHg
-3  (10) -1  (10)
16.Secondary Outcome
Title Change in Total Cholesterol
Hide Description Change in fasting total cholesterol from baseline (week 0) to week 68 (measured as mg/dL) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time Frame Baseline (week 0) to week 68
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomised participants. 'Overall Number of Participants Analyzed' = participants with available data.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.
Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Overall Number of Participants Analyzed 363 181
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio of fasting total cholesterol
0.96
(15.0%)
1.01
(12.3%)
17.Secondary Outcome
Title Change in High-density Lipoproteins (HDL)
Hide Description Change in fasting HDL from baseline (week 0) to week 68 (measured as mg/dL) is presented as ratio to baseline.The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time Frame Baseline (week 0) to week 68
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomised participants. 'Overall Number of Participants Analyzed' = participants with available data.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.
Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Overall Number of Participants Analyzed 363 181
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio of fasting HDL cholesterol
1.06
(14.6%)
1.05
(15.0%)
18.Secondary Outcome
Title Change in Low-density Lipoproteins (LDL)
Hide Description Change in fasting LDL from baseline (week 0) to week 68 (measured as mg/dL) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time Frame Baseline (week 0) to week 68
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomised participants. 'Overall Number of Participants Analyzed' = participants with available data.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.
Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Overall Number of Participants Analyzed 363 181
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio of fasting LDL cholesterol
0.96
(23.2%)
1.01
(18.6%)
19.Secondary Outcome
Title Change in Very Low Density Lipoprotein (VLDL)
Hide Description Change in fasting VLDL from baseline (week 0) to week 68 (measured as mg/dL) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time Frame Baseline (week 0) to week 68
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomised participants. 'Overall Number of Participants Analyzed' = participants with available data.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.
Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Overall Number of Participants Analyzed 363 181
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio of fasting VLDL cholesterol
0.77
(40.9%)
0.91
(38.6%)
20.Secondary Outcome
Title Change in Free Fatty Acids
Hide Description Change in fasting free fatty acids from baseline (week 0) to week 68 (measured as mg/dL) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time Frame Baseline (week 0) to week 68
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomised participants. 'Overall Number of Participants Analyzed' = participants with available data.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.
Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Overall Number of Participants Analyzed 346 171
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio of fasting free fatty acids
0.86
(69.9%)
1.08
(71.8%)
21.Secondary Outcome
Title Change in Triglycerides
Hide Description Change in fasting triglycerides from baseline (week 0) to week 68 (measured as mg/dL) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time Frame Baseline (week 0) to week 68
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomised participants. 'Overall Number of Participants Analyzed' = participants with available data.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.
Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Overall Number of Participants Analyzed 363 181
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio of fasting triglycerides
0.77
(41.3%)
0.91
(39.1%)
22.Secondary Outcome
Title Change in High Sensitivity C-reactive Protein
Hide Description Change in high sensitivity C-reactive protein from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time Frame Baseline (week 0) to week 68
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomised participants. 'Overall Number of Participants Analyzed' = participants with available data.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.
Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Overall Number of Participants Analyzed 363 182
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: milligrams per litre (mg/L)
0.40
(108.7%)
0.76
(75.5%)
23.Secondary Outcome
Title Change in Plasminogen Activator Inhibitor-1 Activity
Hide Description Change in plasminogen activator inhibitor-1 activity from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time Frame Baseline (week 0) to week 68
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomised participants. 'Overall Number of Participants Analyzed' = participants with available data.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.
Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Overall Number of Participants Analyzed 343 162
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Arbritary units per milliliter (AU/ml)
0.92
(80.6%)
1.26
(74.2%)
24.Secondary Outcome
Title Participants Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score
Hide Description The observed number of participants experiencing a meaningful within participant improvement in SF-36 Physical function after 68 weeks was determined based on two thresholds. The threshold of 4.3 is the default generic responder threshold defined in SF-36 manual for a general population. The threshold of 3.7 is specific for overweight or obese population included in the study and calculated using patient global rating anchor questionnaires to reflect participants' own perspective based on Food and Drug Administration (FDA) recommendations. In the reported data, "Yes" infers number of participants who have achieved an improvement in score greater than or equal to the threshold and "No" infers number of participants who have not achieved an improvement in score greater than or equal to the threshold. The endpoint was evaluated based on the in-trial observation period which is uninterrupted time interval from randomization (week 0) to last trial related subject-site contact (week 75).
Time Frame After 68 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomised participants. 'Overall Number of Participants Analyzed' = participants with available data.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.
Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Overall Number of Participants Analyzed 364 181
Measure Type: Count of Participants
Unit of Measure: Participants
Yes (with threshold 4.3)
86
  23.6%
36
  19.9%
No (with threshold 4.3)
278
  76.4%
145
  80.1%
Yes (with threshold 3.7)
133
  36.5%
51
  28.2%
No (with threshold 3.7)
231
  63.5%
130
  71.8%
25.Secondary Outcome
Title Change in Body Weight
Hide Description Change in body weight from baseline (week 0) to week 8 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time Frame Baseline (week 0) to week 8
Hide Outcome Measure Data
Hide Analysis Population Description
FAS included all randomised participants. 'Overall Number of Participants Analyzed' = participants with available data.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.
Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Overall Number of Participants Analyzed 396 197
Mean (Standard Deviation)
Unit of Measure: Percentage
-7.8  (3.1) -6.0  (3.6)
26.Secondary Outcome
Title Number of Treatment-emergent Adverse Events (AEs)
Hide Description An adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. All AEs mentioned here are treatment emergent adverse events (TEAE) defined as an event that had onset date (or increase in severity) on or after the first day of exposure to treatment. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 7 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 7 consecutive missed doses (off-treatment period).
Time Frame Baseline (week 0) to week 75
Hide Outcome Measure Data
Hide Analysis Population Description
SAS included all participants who received at least one dose of trial product.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.
Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Overall Number of Participants Analyzed 407 204
Measure Type: Number
Unit of Measure: events
4035 1325
27.Secondary Outcome
Title Number of Serious Adverse Events (SAEs)
Hide Description A serious adverse event (SAE) is defined as any untoward medical occurrence that at any dose results in death, or is life-threatening, or requires inpatient hospitalization or causes prolongation of existing hospitalization results in persistent or significant disability/incapacity, or may have caused a congenital anomaly/birth defect, or requires intervention to prevent permanent impairment or damage. The SAEs occurred from week 0 to week 75 is presented. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 7 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 7 consecutive missed doses (off-treatment period).
Time Frame Baseline (week 0) to week 75
Hide Outcome Measure Data
Hide Analysis Population Description
SAS included all participants who received at least one dose of trial product.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.
Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Overall Number of Participants Analyzed 407 204
Measure Type: Number
Unit of Measure: events
55 7
28.Secondary Outcome
Title Change in Pulse
Hide Description Change in pulse from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).
Time Frame Baseline (week 0) to week 68
Hide Outcome Measure Data
Hide Analysis Population Description
SAS included all participants who received at least one dose of trial product. Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.
Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Overall Number of Participants Analyzed 334 163
Mean (Standard Deviation)
Unit of Measure: beats per minute (bpm)
3  (11) 2  (10)
29.Secondary Outcome
Title Change in Amylase
Hide Description Change in amylase (measured as U/L) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).
Time Frame Baseline (week 0) to week 68
Hide Outcome Measure Data
Hide Analysis Population Description
SAS included all participants who received at least one dose of trial product. Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.
Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Overall Number of Participants Analyzed 332 161
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio of amylase
1.12
(19%)
1.07
(18.1%)
30.Secondary Outcome
Title Change in Lipase
Hide Description Change in lipase (measured as U/L) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).
Time Frame Baseline (week 0) to week 68
Hide Outcome Measure Data
Hide Analysis Population Description
SAS included all participants who received at least one dose of trial product. Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.
Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Overall Number of Participants Analyzed 332 161
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio of lipase
1.31
(52%)
0.94
(39.4%)
31.Secondary Outcome
Title Change in Calcitonin
Hide Description Change in calcitonin (measured as ng/L) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).
Time Frame Baseline (week 0) to week 68
Hide Outcome Measure Data
Hide Analysis Population Description
SAS included all participants who received at least one dose of trial product. Overall number of participants analyzed = number of participants with available data.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.
Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Overall Number of Participants Analyzed 332 162
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio of calcitonin
0.93
(40.6%)
0.94
(33.2%)
Time Frame week 0 to week 75 Results are based on the SAS which included all participants who received at least one dose of semaglutide or placebo.
Adverse Event Reporting Description All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomised treatment and no later than the date of last dose + 7 weeks.
 
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment. Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
All-Cause Mortality
Semaglutide 2.4 mg Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/407 (0.00%)      0/204 (0.00%)    
Hide Serious Adverse Events
Semaglutide 2.4 mg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   37/407 (9.09%)      6/204 (2.94%)    
Blood and lymphatic system disorders     
Iron deficiency anaemia  1  1/407 (0.25%)  1 0/204 (0.00%)  0
Ear and labyrinth disorders     
Vertigo  1  1/407 (0.25%)  1 0/204 (0.00%)  0
Gastrointestinal disorders     
Abdominal pain  1  1/407 (0.25%)  1 0/204 (0.00%)  0
Haemorrhoids thrombosed  1  1/407 (0.25%)  1 0/204 (0.00%)  0
Incarcerated inguinal hernia  1  0/407 (0.00%)  0 1/204 (0.49%)  1
Inguinal hernia  1  0/407 (0.00%)  0 1/204 (0.49%)  1
Small intestinal obstruction  1  0/407 (0.00%)  0 1/204 (0.49%)  1
General disorders     
Non-cardiac chest pain  1  1/407 (0.25%)  1 0/204 (0.00%)  0
Hepatobiliary disorders     
Biliary dyskinesia  1  1/407 (0.25%)  1 0/204 (0.00%)  0
Cholecystitis  1  2/407 (0.49%)  2 0/204 (0.00%)  0
Cholecystitis acute  1  3/407 (0.74%)  3 0/204 (0.00%)  0
Cholelithiasis  1  7/407 (1.72%)  7 0/204 (0.00%)  0
Infections and infestations     
Abdominal abscess  1  1/407 (0.25%)  1 0/204 (0.00%)  0
Appendicitis  1  3/407 (0.74%)  4 0/204 (0.00%)  0
Cellulitis  1  1/407 (0.25%)  1 0/204 (0.00%)  0
Gastroenteritis viral  1  1/407 (0.25%)  1 0/204 (0.00%)  0
Large intestine infection  1  1/407 (0.25%)  1 0/204 (0.00%)  0
Pelvic inflammatory disease  1  1/407 (0.25%)  1 0/204 (0.00%)  0
Pneumonia  1  1/407 (0.25%)  1 0/204 (0.00%)  0
Sepsis  1  1/407 (0.25%)  1 0/204 (0.00%)  0
Urinary tract infection  1  1/407 (0.25%)  1 0/204 (0.00%)  0
Injury, poisoning and procedural complications     
Hip fracture  1  1/407 (0.25%)  1 0/204 (0.00%)  0
Joint dislocation  1  1/407 (0.25%)  1 0/204 (0.00%)  0
Overdose  1  1/407 (0.25%)  1 0/204 (0.00%)  0
Spinal compression fracture  1  1/407 (0.25%)  1 0/204 (0.00%)  0
Upper limb fracture  1  0/407 (0.00%)  0 1/204 (0.49%)  1
Metabolism and nutrition disorders     
Hypokalaemia  1  1/407 (0.25%)  1 0/204 (0.00%)  0
Obesity  1  0/407 (0.00%)  0 1/204 (0.49%)  1
Musculoskeletal and connective tissue disorders     
Back pain  1  1/407 (0.25%)  1 0/204 (0.00%)  0
Cervical spinal stenosis  1  2/407 (0.49%)  2 0/204 (0.00%)  0
Intervertebral disc protrusion  1  1/407 (0.25%)  1 0/204 (0.00%)  0
Osteoarthritis  1  3/407 (0.74%)  4 0/204 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Breast cancer  1  1/407 (0.25%)  1 0/204 (0.00%)  0
Castleman's disease  1  0/407 (0.00%)  0 1/204 (0.49%)  1
Invasive lobular breast carcinoma  1  0/407 (0.00%)  0 1/204 (0.49%)  1
Papillary thyroid cancer  1  1/407 (0.25%)  1 0/204 (0.00%)  0
Uterine leiomyoma  1  1/407 (0.25%)  1 0/204 (0.00%)  0
Nervous system disorders     
Cerebral infarction  1  1/407 (0.25%)  1 0/204 (0.00%)  0
Syncope  1  1/407 (0.25%)  1 0/204 (0.00%)  0
Transient ischaemic attack  1  1/407 (0.25%)  1 0/204 (0.00%)  0
Psychiatric disorders     
Anxiety  1  1/407 (0.25%)  1 0/204 (0.00%)  0
Renal and urinary disorders     
Hydronephrosis  1  1/407 (0.25%)  1 0/204 (0.00%)  0
Nephrolithiasis  1  1/407 (0.25%)  1 0/204 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Pulmonary embolism  1  1/407 (0.25%)  1 0/204 (0.00%)  0
Surgical and medical procedures     
Neck dissection  1  1/407 (0.25%)  1 0/204 (0.00%)  0
Vascular disorders     
Deep vein thrombosis  1  1/407 (0.25%)  1 0/204 (0.00%)  0
1
Term from vocabulary, MedDRA 22
Indicates events were collected by systematic assessment
Hide 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   379/407 (93.12%)      177/204 (86.76%)    
Gastrointestinal disorders     
Abdominal distension  1  41/407 (10.07%)  55 20/204 (9.80%)  28
Abdominal pain  1  53/407 (13.02%)  75 10/204 (4.90%)  11
Abdominal pain upper  1  33/407 (8.11%)  45 5/204 (2.45%)  5
Constipation  1  150/407 (36.86%)  210 50/204 (24.51%)  62
Diarrhoea  1  147/407 (36.12%)  307 45/204 (22.06%)  62
Dyspepsia  1  36/407 (8.85%)  47 10/204 (4.90%)  15
Eructation  1  36/407 (8.85%)  52 1/204 (0.49%)  1
Flatulence  1  47/407 (11.55%)  62 23/204 (11.27%)  24
Gastrooesophageal reflux disease  1  25/407 (6.14%)  32 4/204 (1.96%)  4
Nausea  1  237/407 (58.23%)  511 45/204 (22.06%)  60
Vomiting  1  111/407 (27.27%)  212 22/204 (10.78%)  25
General disorders     
Fatigue  1  52/407 (12.78%)  69 15/204 (7.35%)  19
Immune system disorders     
Seasonal allergy  1  12/407 (2.95%)  18 11/204 (5.39%)  14
Infections and infestations     
Gastroenteritis  1  28/407 (6.88%)  32 12/204 (5.88%)  19
Gastroenteritis viral  1  41/407 (10.07%)  46 13/204 (6.37%)  13
Influenza  1  27/407 (6.63%)  32 11/204 (5.39%)  11
Nasopharyngitis  1  90/407 (22.11%)  128 49/204 (24.02%)  70
Sinusitis  1  39/407 (9.58%)  51 26/204 (12.75%)  34
Upper respiratory tract infection  1  85/407 (20.88%)  115 44/204 (21.57%)  65
Urinary tract infection  1  41/407 (10.07%)  60 10/204 (4.90%)  11
Metabolism and nutrition disorders     
Decreased appetite  1  35/407 (8.60%)  36 7/204 (3.43%)  7
Musculoskeletal and connective tissue disorders     
Arthralgia  1  39/407 (9.58%)  54 19/204 (9.31%)  23
Back pain  1  53/407 (13.02%)  67 22/204 (10.78%)  24
Pain in extremity  1  17/407 (4.18%)  17 13/204 (6.37%)  14
Nervous system disorders     
Dizziness  1  52/407 (12.78%)  73 11/204 (5.39%)  14
Headache  1  78/407 (19.16%)  123 20/204 (9.80%)  25
Respiratory, thoracic and mediastinal disorders     
Oropharyngeal pain  1  13/407 (3.19%)  17 12/204 (5.88%)  12
1
Term from vocabulary, MedDRA 22
Indicates events were collected by systematic assessment
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
Layout table for Results Point of Contact information
Name/Title: Clinical Reporting Anchor and Disclosure (1452)
Organization: Novo Nordisk A/S
Phone: (+1) 866-867-7178
EMail: clinicaltrials@novonordisk.com
Layout table for additonal information
Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT03611582    
Other Study ID Numbers: NN9536-4375
U1111-1200-8199 ( Other Identifier: World Health Organization (WHO) )
First Submitted: July 17, 2018
First Posted: August 2, 2018
Results First Submitted: June 16, 2021
Results First Posted: July 9, 2021
Last Update Posted: November 11, 2021