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Two-year Research Study Investigating How Well Semaglutide Works in People Suffering From Overweight or Obesity (STEP 5)

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ClinicalTrials.gov Identifier: NCT03693430
Recruitment Status : Completed
First Posted : October 3, 2018
Results First Posted : March 23, 2022
Last Update Posted : February 17, 2023
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 304
Recruitment Details The trial was conducted at 41 sites in 5 countries as follows: Canada (9 sites), Hungary (6 sites), Italy (5 sites), Spain (6 sites), and United States (15 sites).
Pre-assignment Details Participants were randomized in a 1:1 manner to receive treatment with semaglutide 2.4 milligram (mg) or placebo once weekly as an adjunct to a reduced-calorie diet and increased physical activity. The trial has a 104 weeks treatment period (16 weeks of dose escalation period and 88 weeks of maintenance dose).
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description Participants received once-weekly subcutaneous (s.c) injection of semaglutide 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 88 weeks until week 104. Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Period Title: Overall Study
Started 152 152
Full Analysis Set (FAS) 152 152
Safety Analysis Set (SAS) 152 152
Completed 148 134
Not Completed 4 18
Reason Not Completed
Lost to Follow-up             3             14
Death             1             0
Withdrawal by Subject             0             4
Arm/Group Title Semaglutide 2.4 mg Placebo Total
Hide Arm/Group Description Participants received once-weekly s.c injection of semaglutide 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 88 weeks until week 104. Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks. Total of all reporting groups
Overall Number of Baseline Participants 152 152 304
Hide Baseline Analysis Population Description
The full analysis set (FAS) included all randomised participants according to the intention-to-treat principle.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 152 participants 152 participants 304 participants
47  (12) 47  (10) 47  (11)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 152 participants 152 participants 304 participants
Female
123
  80.9%
113
  74.3%
236
  77.6%
Male
29
  19.1%
39
  25.7%
68
  22.4%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 152 participants 152 participants 304 participants
Hispanic or Latino
18
  11.8%
21
  13.8%
39
  12.8%
Not Hispanic or Latino
134
  88.2%
131
  86.2%
265
  87.2%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 152 participants 152 participants 304 participants
White
141
  92.8%
142
  93.4%
283
  93.1%
Black or African American
7
   4.6%
5
   3.3%
12
   3.9%
Other
0
   0.0%
4
   2.6%
4
   1.3%
American Indian or Alaska Native
2
   1.3%
1
   0.7%
3
   1.0%
Asian
2
   1.3%
0
   0.0%
2
   0.7%
1.Primary Outcome
Title Percentage Change From Baseline (Week 0) to Week 104 in Body Weight
Hide Description Percentage change in body weight for both in-trial and on-treatment observation period from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from both in-trial and on-treatment periods. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site. On-treatment observation period: the interval from first to last trial product administration plus 2 weeks of follow-up and excluding any period of temporary treatment interruption defined as >2 consecutive missed doses (corresponding to >2 weeks off-treatment).
Time Frame From Baseline (Week 0) to Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure and Number Analyzed = participants with available data for each specified category.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants received once-weekly s.c injection of semaglutide 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 88 weeks until week 104.
Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Overall Number of Participants Analyzed 144 128
Mean (Standard Deviation)
Unit of Measure: percentage change
In-trial observation period Number Analyzed 144 participants 128 participants
-15.9  (12.3) -1.9  (8.9)
On-treatment observation period Number Analyzed 132 participants 109 participants
-17.3  (11.9) -2.0  (8.6)
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 Week 104 responses were analysed using an analysis of covariance model with randomised treatment as factor and baseline body weight as covariate. Missing observations were multiple (x1000) imputed from retrieved subjects of the same randomised treatment arm.
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -12.55
Confidence Interval (2-Sided) 95%
-15.33 to -9.77
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 All responses prior to first discontinuation of treatment (or initiation of other anti-obesity medication or bariatric surgery) were included in a mixed model for repeated measurements with randomised treatment as factor and baseline body weight as covariate, all nested within visit.
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 -16.05
Confidence Interval (2-Sided) 95%
-18.64 to -13.45
Estimation Comments [Not Specified]
2.Primary Outcome
Title Number of Participants Who Achieved (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 at 104 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 outcome measure was evaluated based on the data from both in-trial and on-treatment periods. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site. On-treatment observation period: the interval from first to last trial product administration plus 2 weeks of follow-up and excluding any period of temporary treatment interruption defined as >2 consecutive missed doses (corresponding to >2 weeks off-treatment).
Time Frame At Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure and Number Analyzed = participants with available data for each specified category.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants received once-weekly s.c injection of semaglutide 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 88 weeks until week 104.
Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Overall Number of Participants Analyzed 144 128
Measure Type: Count of Participants
Unit of Measure: Participants
In-trial observation period Number Analyzed 144 participants 128 participants
Yes
111
  77.1%
44
  34.4%
No
33
  22.9%
84
  65.6%
On-treatment observation period Number Analyzed 132 participants 109 participants
Yes
110
  83.3%
38
  34.9%
No
22
  16.7%
71
  65.1%
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 4.99
Confidence Interval (2-Sided) 95%
2.95 to 8.42
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
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 18.06
Confidence Interval (2-Sided) 95%
10.04 to 32.49
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Number of Participants Who Achieved (Yes/no): Body Weight Reduction More Than or Equal to 10%
Hide Description Number of participants who achieved >=10% weight loss at 104 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved >=10% weight loss, whereas 'No' infers the number of participants who have not achieved >=10% weight loss. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Time Frame At Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants received once-weekly s.c injection of semaglutide 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 88 weeks until week 104.
Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Overall Number of Participants Analyzed 144 128
Measure Type: Count of Participants
Unit of Measure: Participants
Yes
89
  61.8%
17
  13.3%
No
55
  38.2%
111
  86.7%
4.Secondary Outcome
Title Number of Participants Who Achieved (Yes/no): Body Weight Reduction More Than or Equal to 15%
Hide Description Number of participants who achieved >=15% weight loss at 104 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved >=15% weight loss, whereas 'No' infers the number of participants who have not achieved >=15% weight loss. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Time Frame At Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants received once-weekly s.c injection of semaglutide 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 88 weeks until week 104.
Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Overall Number of Participants Analyzed 144 128
Measure Type: Count of Participants
Unit of Measure: Participants
Yes
75
  52.1%
9
   7.0%
No
69
  47.9%
119
  93.0%
5.Secondary Outcome
Title Number of Participants Who Achieved (Yes/no): Body Weight Reduction More Than or Equal to 20%
Hide Description Number of participants who achieved >=20% weight loss at 104 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved >=20% weight loss, whereas 'No' infers the number of participants who have not achieved >=20% weight loss. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Time Frame At Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants received once-weekly s.c injection of semaglutide 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 88 weeks until week 104.
Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Overall Number of Participants Analyzed 144 128
Measure Type: Count of Participants
Unit of Measure: Participants
Yes
52
  36.1%
3
   2.3%
No
92
  63.9%
125
  97.7%
6.Secondary Outcome
Title Change From Baseline (Week 0) to Week 104 in Waist Circumference
Hide Description Change in waist circumference from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Time Frame From Baseline (Week 0) to Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants received once-weekly s.c injection of semaglutide 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 88 weeks until week 104.
Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Overall Number of Participants Analyzed 143 126
Mean (Standard Deviation)
Unit of Measure: centimeter (cm)
-15.2  (12.4) -4.3  (9.1)
7.Secondary Outcome
Title Change From Baseline (Week 0) to Week 104 in Body Weight (kg)
Hide Description Change in body weight from baseline (week 0) to week 104 in kilogram (kg) is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Time Frame From Baseline (Week 0) to Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants received once-weekly s.c injection of semaglutide 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 88 weeks until week 104.
Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Overall Number of Participants Analyzed 144 128
Mean (Standard Deviation)
Unit of Measure: kilogram
-16.9  (14.0) -2.1  (9.5)
8.Secondary Outcome
Title Change From Baseline (Week 0) to Week 104 in Body Mass Index (BMI)
Hide Description Change in BMI from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Time Frame From Baseline (Week 0) to Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants received once-weekly s.c injection of semaglutide 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 88 weeks until week 104.
Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Overall Number of Participants Analyzed 144 128
Mean (Standard Deviation)
Unit of Measure: kilogram per square meter (kg/m^2)
-6.2  (5.3) -0.7  (3.5)
9.Secondary Outcome
Title Change From Baseline (Week 0) to Week 104 in Systolic Blood Pressure
Hide Description Change in systolic blood pressure from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Time Frame From Baseline (Week 0) to Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants received once-weekly s.c injection of semaglutide 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 88 weeks until week 104.
Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Overall Number of Participants Analyzed 142 125
Mean (Standard Deviation)
Unit of Measure: millimeter of mercury (mmHg)
-6  (13) -1  (15)
10.Secondary Outcome
Title Change From Baseline (Week 0) to Week 104 in Diastolic Blood Pressure
Hide Description Change in diastolic blood pressure from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Time Frame From Baseline (Week 0) to Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants received once-weekly s.c injection of semaglutide 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 88 weeks until week 104.
Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Overall Number of Participants Analyzed 142 125
Mean (Standard Deviation)
Unit of Measure: mmHg
-4  (10) -1  (9)
11.Secondary Outcome
Title Change in Total Cholesterol-ratio to Baseline
Hide Description Change in total cholesterol from baseline (week 0) to week 104 measured in milligrams per deciliter (mg/dL) is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Time Frame From Baseline (Week 0) to Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants received once-weekly s.c injection of semaglutide 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 88 weeks until week 104.
Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Overall Number of Participants Analyzed 141 121
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio of total cholesterol
0.96
(15.3%)
1.02
(13.5%)
12.Secondary Outcome
Title Change in High Density Lipoprotein (HDL) Cholesterol-ratio to Baseline
Hide Description Change in HDL cholesterol from baseline (week 0) to week 104 measured in mg/dL is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Time Frame From Baseline (Week 0) to Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants received once-weekly s.c injection of semaglutide 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 88 weeks until week 104.
Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Overall Number of Participants Analyzed 141 120
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio of HDL cholesterol
1.09
(19.1%)
1.08
(15.4%)
13.Secondary Outcome
Title Change in Low Density Lipoprotein (LDL) Cholesterol-ratio to Baseline
Hide Description Change in LDL cholesterol from baseline (week 0) to week 104 measured in mg/dL is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Time Frame From Baseline (Week 0) to Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants received once-weekly s.c injection of semaglutide 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 88 weeks until week 104.
Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Overall Number of Participants Analyzed 141 121
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio of LDL cholesterol
0.93
(23.8%)
0.99
(19.1%)
14.Secondary Outcome
Title Change in Very Low Density Lipoprotein (VLDL) Cholesterol-ratio to Baseline
Hide Description Change in VLDL cholesterol from baseline (week 0) to week 104 measured in mg/dL is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Time Frame From Baseline (Week 0) to Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants received once-weekly s.c injection of semaglutide 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 88 weeks until week 104.
Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Overall Number of Participants Analyzed 141 121
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio of VLDL cholesterol
0.79
(42.3%)
1.03
(35.1%)
15.Secondary Outcome
Title Change in Free Fatty Acids-ratio to Baseline
Hide Description Change in free fatty acids from baseline (week 0) to week 104 measured in mg/dL is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Time Frame From Baseline (Week 0) to Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants received once-weekly s.c injection of semaglutide 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 88 weeks until week 104.
Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Overall Number of Participants Analyzed 133 111
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio of free fatty acids
0.99
(71.2%)
1.07
(69.1%)
16.Secondary Outcome
Title Change in Triglycerides-ratio to Baseline
Hide Description Change in triglycerides from baseline (week 0) to week 104 measured in mg/dL is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Time Frame From Baseline (Week 0) to Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants received once-weekly s.c injection of semaglutide 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 88 weeks until week 104.
Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Overall Number of Participants Analyzed 141 121
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio of triglycerides
0.79
(42.4%)
1.03
(36.0%)
17.Secondary Outcome
Title Change in High Sensitivity C-reactive Protein (hsCRP)-Ratio to Baseline
Hide Description Change in hsCRP from baseline (week 0) to week 104 measured in mg/dL is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Time Frame From Baseline (Week 0) to Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants received once-weekly s.c injection of semaglutide 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 88 weeks until week 104.
Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Overall Number of Participants Analyzed 141 121
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio of hsCRP
0.41
(149.1%)
0.99
(105.5%)
18.Secondary Outcome
Title Change in Glycated Haemoglobin (HbA1c) (Percent [%])
Hide Description Change in HbA1c from baseline (week 0) to week 104 in % is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Time Frame From Baseline (Week 0) to Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants received once-weekly s.c injection of semaglutide 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 88 weeks until week 104.
Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Overall Number of Participants Analyzed 141 122
Mean (Standard Deviation)
Unit of Measure: Percent of glycated haemoglobin
-0.5  (0.3) -0.1  (0.3)
19.Secondary Outcome
Title Change From Baseline (Week 0) to Week 104 in HbA1c (mmol/Mol)
Hide Description Change in HbA1c from baseline (week 0) to week 104 in millimole per mole (mmol/mol) is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Time Frame From Baseline (Week 0) to Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants received once-weekly s.c injection of semaglutide 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 88 weeks until week 104.
Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Overall Number of Participants Analyzed 141 122
Mean (Standard Deviation)
Unit of Measure: mmol/mol
-5.1  (3.2) -1.0  (3.0)
20.Secondary Outcome
Title Change From Baseline (Week 0) to Week 104 in Fasting Plasma Glucose (FPG) (mmol/L)
Hide Description Change in FPG from baseline (week 0) to week 104 in millimoles per liter (mmol/L) is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Time Frame From Baseline (Week 0) to Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants received once-weekly s.c injection of semaglutide 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 88 weeks until week 104.
Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Overall Number of Participants Analyzed 137 117
Mean (Standard Deviation)
Unit of Measure: mmol/L
-0.5  (0.5) 0.1  (0.6)
21.Secondary Outcome
Title Change From Baseline (Week 0) to Week 104 in FPG (mg/dL)
Hide Description Change in FPG from baseline (week 0) to week 104 in mg/dL is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Time Frame From Baseline (Week 0) to Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants received once-weekly s.c injection of semaglutide 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 88 weeks until week 104.
Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Overall Number of Participants Analyzed 137 117
Mean (Standard Deviation)
Unit of Measure: mg/dL
-8.3  (9.6) 1.8  (10.8)
22.Secondary Outcome
Title Change in Fasting Serum Insulin-ratio to Baseline (Pmol/L)
Hide Description Change in fasting serum insulin from baseline (week 0) to week 104 measured in picomole per liter (pmol) is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Time Frame From Baseline (Week 0) to Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants received once-weekly s.c injection of semaglutide 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 88 weeks until week 104.
Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Overall Number of Participants Analyzed 131 110
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio of fasting serum insulin
0.68
(54.1%)
0.96
(62.9%)
23.Secondary Outcome
Title Change in Fasting Serum Insulin-ratio to Baseline (mIU/mL)
Hide Description Change in fasting serum insulin from baseline (week 0) to week 104 measured in milli-international units per milliliter (mIU/mL) is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Time Frame From Baseline (Week 0) to Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants received once-weekly s.c injection of semaglutide 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 88 weeks until week 104.
Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Overall Number of Participants Analyzed 131 110
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio of fasting serum insulin
0.68
(54.1%)
0.96
(62.9%)
24.Secondary Outcome
Title Percentage Change From Baseline (Week 0) to Week 52 in Body Weight
Hide Description Percentage change in body weight from baseline (week 0) to week 52 is presented.
Time Frame From Baseline (Week 0) to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants received once-weekly s.c injection of semaglutide 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 88 weeks until week 104.
Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Overall Number of Participants Analyzed 149 129
Mean (Standard Deviation)
Unit of Measure: percentage change
-15.8  (9.3) -3.3  (6.4)
25.Secondary Outcome
Title Change From Baseline (Week 0) to Week 52 in Body Weight (kg)
Hide Description Change in body weight from baseline (week 0) to week 52 in kg is presented.
Time Frame From Baseline (Week 0) to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants received once-weekly s.c injection of semaglutide 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 88 weeks until week 104.
Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Overall Number of Participants Analyzed 149 129
Mean (Standard Deviation)
Unit of Measure: kilogram (kg)
-16.7  (10.3) -3.5  (7.4)
26.Secondary Outcome
Title Change From Baseline (Week 0) to Week 52 in Body Mass Index (BMI)
Hide Description Change in BMI from baseline (week 0) to week 52 is presented.
Time Frame From Baseline (Week 0) to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants received once-weekly s.c injection of semaglutide 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 88 weeks until week 104.
Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Overall Number of Participants Analyzed 149 129
Mean (Standard Deviation)
Unit of Measure: kilogram per square meter (kg/m^2)
-6.1  (3.8) -1.3  (2.6)
27.Secondary Outcome
Title Change From Baseline (Week 0) to Week 52 in Waist Circumference
Hide Description Change in waist circumference from baseline (week 0) to week 52 is presented.
Time Frame From Baseline (Week 0) to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants received once-weekly s.c injection of semaglutide 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 88 weeks until week 104.
Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Overall Number of Participants Analyzed 149 129
Mean (Standard Deviation)
Unit of Measure: centimeter (cm)
-14.3  (9.4) -4.5  (6.8)
28.Secondary Outcome
Title Number of Participants Who at 52 Weeks Achieved (Yes/no): Body Weight Reduction More Than or Equal to 5%
Hide Description Number of participants who achieved >=5% weight loss at 52 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.
Time Frame At Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants received once-weekly s.c injection of semaglutide 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 88 weeks until week 104.
Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Overall Number of Participants Analyzed 149 129
Measure Type: Count of Participants
Unit of Measure: Participants
Yes
132
  88.6%
38
  29.5%
No
17
  11.4%
91
  70.5%
29.Secondary Outcome
Title Number of Participants Who at 52 Weeks Achieved (Yes/no): Body Weight Reduction More Than or Equal to 10%
Hide Description Number of participants who achieved >=10% weight loss at 52 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved >=10% weight loss, whereas 'No' infers the number of participants who have not achieved >=10% weight loss.
Time Frame At Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants received once-weekly s.c injection of semaglutide 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 88 weeks until week 104.
Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Overall Number of Participants Analyzed 149 129
Measure Type: Count of Participants
Unit of Measure: Participants
Yes
102
  68.5%
17
  13.2%
No
47
  31.5%
112
  86.8%
30.Secondary Outcome
Title Number of Participants Who at 52 Weeks Achieved (Yes/no): Body Weight Reduction More Than or Equal to 15%
Hide Description Number of participants who achieved >=15% weight loss at 52 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved >=15% weight loss, whereas 'No' infers the number of participants who have not achieved >=15% weight loss.
Time Frame At Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants received once-weekly s.c injection of semaglutide 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 88 weeks until week 104.
Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Overall Number of Participants Analyzed 149 129
Measure Type: Count of Participants
Unit of Measure: Participants
Yes
78
  52.3%
7
   5.4%
No
71
  47.7%
122
  94.6%
31.Secondary Outcome
Title Number of Participants Who at 52 Weeks Achieved (Yes/no): Body Weight Reduction More Than or Equal to 20%
Hide Description Number of participants who achieved >=20% weight loss at 52 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved >=20% weight loss, whereas 'No' infers the number of participants who have not achieved >=20% weight loss.
Time Frame At Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants received once-weekly s.c injection of semaglutide 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 88 weeks until week 104.
Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Overall Number of Participants Analyzed 149 129
Measure Type: Count of Participants
Unit of Measure: Participants
Yes
52
  34.9%
3
   2.3%
No
97
  65.1%
126
  97.7%
32.Secondary Outcome
Title Number of Treatment-emergent Adverse Events (TEAEs)
Hide Description An adverse event (AE) was defined as any unfavourable 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 TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to treatment. The outcome measure was evaluated based on the data from on-treatment observation period, which was defined as the interval from first to last trial product administration plus 7 weeks of follow-up and excluding any period of temporary treatment interruption defined as >7 consecutive missed doses (corresponding to >7 weeks off-treatment).
Time Frame From Baseline (Week 0) to Week 111
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set (SAS) included all randomised participants exposed to at least one dose of randomised treatment.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants received once-weekly s.c injection of semaglutide 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 88 weeks until week 104.
Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Overall Number of Participants Analyzed 152 152
Measure Type: Number
Unit of Measure: events
1645 1059
33.Secondary Outcome
Title Number of Serious Adverse Events (SAEs)
Hide Description A SAE was 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 111 is presented. The outcome measure was evaluated based on the data from on-treatment observation period, which was defined as the interval from first to last trial product administration plus 7 weeks of follow-up and excluding any period of temporary treatment interruption defined as >7 consecutive missed doses (corresponding to >7 weeks off-treatment).
Time Frame From Baseline (Week 0) to Week 111
Hide Outcome Measure Data
Hide Analysis Population Description
The SAS included all randomised participants exposed to at least one dose of randomised treatment.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants received once-weekly s.c injection of semaglutide 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 88 weeks until week 104.
Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Overall Number of Participants Analyzed 152 152
Measure Type: Number
Unit of Measure: events
18 20
34.Secondary Outcome
Title Change From Baseline (Week 0) to Week 104 in Pulse
Hide Description Change in pulse from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from on-treatment observation period, which was defined as the interval from first to last trial product administration plus 2 weeks of follow-up and excluding any period of temporary treatment interruption defined as >2 consecutive missed doses (corresponding to >2 weeks off-treatment).
Time Frame From Baseline (Week 0) to Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
The SAS included all randomised participants exposed to at least one dose of randomised treatment. Overall Number of Participants Analyzed = participants with available data for this outcome measure.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants received once-weekly s.c injection of semaglutide 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 88 weeks until week 104.
Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Overall Number of Participants Analyzed 130 106
Mean (Standard Deviation)
Unit of Measure: beats per minute (beats/min)
3  (10) -1  (9)
35.Secondary Outcome
Title Change From Baseline (Week 0) to Week 104 in Amylase
Hide Description Change in amylase from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from on-treatment observation period, which was defined as the interval from first to last trial product administration plus 2 weeks of follow-up and excluding any period of temporary treatment interruption defined as >2 consecutive missed doses (corresponding to >2 weeks off-treatment).
Time Frame From Baseline (Week 0) to Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
The SAS included all randomised participants exposed to at least one dose of randomised treatment. Overall Number of Participants Analyzed = participants with available data for this outcome measure.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants received once-weekly s.c injection of semaglutide 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 88 weeks until week 104.
Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Overall Number of Participants Analyzed 130 106
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Units/liter (U/L)
1.13
(20.7%)
1.02
(15.1%)
36.Secondary Outcome
Title Change From Baseline (Week 0) to Week 104 in Lipase
Hide Description Change in lipase from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from on-treatment observation period, which was defined as the interval from first to last trial product administration plus 2 weeks of follow-up and excluding any period of temporary treatment interruption defined as >2 consecutive missed doses (corresponding to >2 weeks off-treatment).
Time Frame From Baseline (Week 0) to Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
The SAS included all randomised participants exposed to at least one dose of randomised treatment. Overall Number of Participants Analyzed = participants with available data for this outcome measure.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants received once-weekly s.c injection of semaglutide 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 88 weeks until week 104.
Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Overall Number of Participants Analyzed 130 106
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: U/L
1.47
(52.3%)
1.00
(34.4%)
37.Secondary Outcome
Title Change From Baseline (Week 0) to Week 104 in Calcitonin
Hide Description Change in calcitonin from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from on-treatment observation period, which was defined as the interval from first to last trial product administration plus 2 weeks of follow-up and excluding any period of temporary treatment interruption defined as >2 consecutive missed doses (corresponding to >2 weeks off-treatment).
Time Frame From Baseline (Week 0) to Week 104
Hide Outcome Measure Data
Hide Analysis Population Description
The SAS included all randomised participants exposed to at least one dose of randomised treatment. Overall Number of Participants Analyzed = participants with available data for this outcome measure.
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description:
Participants received once-weekly s.c injection of semaglutide 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 88 weeks until week 104.
Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Overall Number of Participants Analyzed 124 102
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanogram per liter (ng/L)
0.99
(21.5%)
0.97
(41.0%)
Time Frame From Baseline (Week 0) to Week 111
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 randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
 
Arm/Group Title Semaglutide 2.4 mg Placebo
Hide Arm/Group Description Participants received once-weekly s.c injection of semaglutide 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 88 weeks until week 104. Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
All-Cause Mortality
Semaglutide 2.4 mg Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   1/152 (0.66%)      0/152 (0.00%)    
Hide Serious Adverse Events
Semaglutide 2.4 mg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   12/152 (7.89%)      18/152 (11.84%)    
Cardiac disorders     
Acute myocardial infarction † 1  1/152 (0.66%)  1 0/152 (0.00%)  0
Congenital, familial and genetic disorders     
Arnold-Chiari malformation † 1  0/152 (0.00%)  0 1/152 (0.66%)  1
Gastrointestinal disorders     
Abdominal adhesions † 1  1/152 (0.66%)  1 0/152 (0.00%)  0
Gastritis † 1  0/152 (0.00%)  0 1/152 (0.66%)  1
Gastrooesophageal reflux disease † 1  1/152 (0.66%)  1 0/152 (0.00%)  0
Hepatobiliary disorders     
Cholecystitis † 1  1/152 (0.66%)  1 0/152 (0.00%)  0
Cholecystitis acute † 1  1/152 (0.66%)  1 0/152 (0.00%)  0
Cholelithiasis † 1  2/152 (1.32%)  2 0/152 (0.00%)  0
Infections and infestations     
Anal abscess † 1  0/152 (0.00%)  0 1/152 (0.66%)  1
Appendicitis † 1  0/152 (0.00%)  0 1/152 (0.66%)  1
Appendicitis perforated † 1  1/152 (0.66%)  1 0/152 (0.00%)  0
COVID-19 † 1  1/152 (0.66%)  1 2/152 (1.32%)  2
COVID-19 pneumonia † 1  0/152 (0.00%)  0 1/152 (0.66%)  1
Colonic abscess † 1  1/152 (0.66%)  1 0/152 (0.00%)  0
Diverticulitis † 1  1/152 (0.66%)  1 0/152 (0.00%)  0
Herpes zoster † 1  0/152 (0.00%)  0 1/152 (0.66%)  1
Perineal abscess † 1  1/152 (0.66%)  1 0/152 (0.00%)  0
Pneumonia † 1  0/152 (0.00%)  0 1/152 (0.66%)  1
Injury, poisoning and procedural complications     
Jaw fracture † 1  0/152 (0.00%)  0 1/152 (0.66%)  1
Rib fracture † 1  0/152 (0.00%)  0 1/152 (0.66%)  1
Musculoskeletal and connective tissue disorders     
Foot deformity † 1  1/152 (0.66%)  1 1/152 (0.66%)  1
Rotator cuff syndrome † 1  0/152 (0.00%)  0 1/152 (0.66%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Benign uterine neoplasm † 1  1/152 (0.66%)  1 0/152 (0.00%)  0
Invasive ductal breast carcinoma † 1  0/152 (0.00%)  0 2/152 (1.32%)  2
Lung adenocarcinoma † 1  0/152 (0.00%)  0 1/152 (0.66%)  1
Small cell lung cancer metastatic † 1  0/152 (0.00%)  0 1/152 (0.66%)  1
Nervous system disorders     
Cervical cord compression † 1  0/152 (0.00%)  0 1/152 (0.66%)  1
Tension headache † 1  0/152 (0.00%)  0 1/152 (0.66%)  1
Psychiatric disorders     
Panic disorder † 1  1/152 (0.66%)  1 0/152 (0.00%)  0
Renal and urinary disorders     
Nephrolithiasis † 1  1/152 (0.66%)  1 0/152 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Pulmonary embolism † 1  1/152 (0.66%)  1 0/152 (0.00%)  0
Surgical and medical procedures     
Thyroidectomy † 1  0/152 (0.00%)  0 1/152 (0.66%)  1
Vascular disorders     
Deep vein thrombosis † 1  1/152 (0.66%)  1 0/152 (0.00%)  0
1
Term from vocabulary, MedDRA 23
†
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   141/152 (92.76%)      117/152 (76.97%)    
Gastrointestinal disorders     
Abdominal distension † 1  15/152 (9.87%)  22 9/152 (5.92%)  13
Abdominal pain † 1  20/152 (13.16%)  32 4/152 (2.63%)  14
Abdominal pain upper † 1  22/152 (14.47%)  23 10/152 (6.58%)  13
Constipation † 1  47/152 (30.92%)  62 17/152 (11.18%)  26
Diarrhoea † 1  53/152 (34.87%)  108 36/152 (23.68%)  51
Dyspepsia † 1  20/152 (13.16%)  24 7/152 (4.61%)  12
Eructation † 1  17/152 (11.18%)  21 1/152 (0.66%)  2
Flatulence † 1  20/152 (13.16%)  25 10/152 (6.58%)  11
Gastrooesophageal reflux disease † 1  15/152 (9.87%)  19 6/152 (3.95%)  6
Nausea † 1  81/152 (53.29%)  213 33/152 (21.71%)  53
Vomiting † 1  46/152 (30.26%)  78 7/152 (4.61%)  8
General disorders     
Asthenia † 1  8/152 (5.26%)  10 2/152 (1.32%)  3
Fatigue † 1  11/152 (7.24%)  12 8/152 (5.26%)  8
Injection site bruising † 1  5/152 (3.29%)  8 8/152 (5.26%)  11
Infections and infestations     
Bronchitis † 1  8/152 (5.26%)  9 8/152 (5.26%)  9
COVID-19 † 1  15/152 (9.87%)  16 6/152 (3.95%)  6
Gastroenteritis † 1  20/152 (13.16%)  28 4/152 (2.63%)  4
Influenza † 1  20/152 (13.16%)  23 16/152 (10.53%)  19
Nasopharyngitis † 1  24/152 (15.79%)  33 23/152 (15.13%)  31
Sinusitis † 1  8/152 (5.26%)  8 9/152 (5.92%)  9
Upper respiratory tract infection † 1  20/152 (13.16%)  31 23/152 (15.13%)  30
Urinary tract infection † 1  12/152 (7.89%)  19 6/152 (3.95%)  7
Injury, poisoning and procedural complications     
Ligament sprain † 1  10/152 (6.58%)  10 1/152 (0.66%)  1
Metabolism and nutrition disorders     
Decreased appetite † 1  17/152 (11.18%)  18 6/152 (3.95%)  6
Musculoskeletal and connective tissue disorders     
Arthralgia † 1  14/152 (9.21%)  20 11/152 (7.24%)  20
Back pain † 1  15/152 (9.87%)  17 19/152 (12.50%)  20
Osteoarthritis † 1  9/152 (5.92%)  10 8/152 (5.26%)  9
Nervous system disorders     
Dizziness † 1  13/152 (8.55%)  16 8/152 (5.26%)  12
Headache † 1  16/152 (10.53%)  36 16/152 (10.53%)  31
Psychiatric disorders     
Anxiety † 1  8/152 (5.26%)  8 11/152 (7.24%)  12
Respiratory, thoracic and mediastinal disorders     
Cough † 1  8/152 (5.26%)  8 8/152 (5.26%)  10
Vascular disorders     
Hypertension † 1  6/152 (3.95%)  6 14/152 (9.21%)  14
1
Term from vocabulary, MedDRA 23
†
Indicates events were collected by systematic assessment
[Not Specified]
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 Office (1452)
Organization: Novo Nordisk A/S
Phone: (+1) 866-867-7178
EMail: clinicaltrials@novonordisk.com
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT03693430    
Other Study ID Numbers: NN9536-4378
2017-003726-32 ( Registry Identifier: European Medicines Agency (EudraCT) )
U1111-1202-1740 ( Other Identifier: World Health Organization (WHO) )
First Submitted: October 1, 2018
First Posted: October 3, 2018
Results First Submitted: February 2, 2022
Results First Posted: March 23, 2022
Last Update Posted: February 17, 2023