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Research Study Investigating How Well Semaglutide Works in People Suffering From Overweight or Obesity (STEP 4)

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ClinicalTrials.gov Identifier: NCT03548987
Recruitment Status : Completed
First Posted : June 7, 2018
Results First Posted : March 15, 2021
Last Update Posted : March 15, 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 Metabolism and Nutrition Disorder
Obesity
Interventions Drug: Semaglutide
Drug: Placebo
Enrollment 902
Recruitment Details The trial was conducted in 73 sites in Denmark (2), Israel (6), Netherlands (3), Portugal (6), South Africa (6), Spain (7), Sweden (4), Switzerland (6), Ukraine (5) and United States (28).
Pre-assignment Details The trial included 20-week run-in period and 48-week maintenance period. During the run-in period, participant started with a semaglutide dose of 0.25 mg and the dose was increased every fourth week until the target dose, 2.4 mg was reached. Out of 902 participants, 803 have completed the run-in period. Thus, these were randomised in 2:1 ratio either to receive semaglutide 2.4 mg or placebo. The treatment is an adjunct to reduced-calorie diet and increased physical activity.
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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68. Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Period Title: Run-in Period (Week 0 to Week 20)
Started 902 0
Safety Analysis Set (SAS) 902 0
Completed 803 0
Not Completed 99 0
Reason Not Completed
Other             9             0
Lost to Follow-up             8             0
Withdrawal by Subject             11             0
Safety concern as judged by investigator             2             0
Run-in failure             19             0
Pregnancy             1             0
Protocol Violation             1             0
Adverse Event             48             0
Period Title: Maintenance Period (Week 20 to Week 68)
Started 535 268
Full Analysis Set (FAS) 535 268
Completed 504 237
Not Completed 31 31
Reason Not Completed
other             12             23
Lost to Follow-up             2             1
Withdrawal by Subject             1             1
Pregnancy             2             0
Protocol Violation             1             0
Adverse Event             13             6
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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68. Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68. Total of all reporting groups
Overall Number of Baseline Participants 535 268 803
Hide Baseline Analysis Population Description
Full analysis set (FAS) included all randomised participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 535 participants 268 participants 803 participants
47  (12) 46  (12) 46  (12)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 535 participants 268 participants 803 participants
Female
429
  80.2%
205
  76.5%
634
  79.0%
Male
106
  19.8%
63
  23.5%
169
  21.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 535 participants 268 participants 803 participants
Hispanic or Latino
42
   7.9%
21
   7.8%
63
   7.8%
Not Hispanic or Latino
493
  92.1%
247
  92.2%
740
  92.2%
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 535 participants 268 participants 803 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
15
   2.8%
4
   1.5%
19
   2.4%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
69
  12.9%
35
  13.1%
104
  13.0%
White
446
  83.4%
226
  84.3%
672
  83.7%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
5
   0.9%
3
   1.1%
8
   1.0%
1.Primary Outcome
Title Change From Randomisation to Week 68 in Body Weight (%)
Hide Description Change in body weight from baseline (week 20) to week 68 is presented. 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 run-in (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 Randomisation (week 20) to week 68
Hide Outcome Measure Data
Hide Analysis Population Description
Overall number of participants analyzed = FAS which comprised all randomised participants. Number 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.
Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Overall Number of Participants Analyzed 535 268
Mean (Standard Deviation)
Unit of Measure: Percentage point
In-trial Number Analyzed 535 participants 268 participants
-8.3  (8.1) 6.5  (7.7)
On-treatment Number Analyzed 495 participants 234 participants
-8.8  (7.8) 6.1  (7.7)
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 ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -14.75
Confidence Interval (2-Sided) 95%
-16.00 to -13.50
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 Other
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 -15.33
Confidence Interval (2-Sided) 95%
-16.52 to -14.13
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change in Waist Circumference
Hide Description Change in waist circumference from baseline (week 20) 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame Randomization (week 20) 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.
Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Overall Number of Participants Analyzed 518 248
Mean (Standard Deviation)
Unit of Measure: Centimeter (cm)
-6.9  (7.5) 3.2  (7.0)
3.Secondary Outcome
Title Change in Systolic Blood Pressure
Hide Description Change in systolic blood pressure from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame Randomization (week 20) 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.
Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Overall Number of Participants Analyzed 518 248
Mean (Standard Deviation)
Unit of Measure: Millimeters of mercury (mmHg)
0  (14) 5  (13)
4.Secondary Outcome
Title Change in Diastolic Blood Pressure
Hide Description Change in diastolic blood pressure from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame Randomization (week 20) 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.
Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Overall Number of Participants Analyzed 518 248
Mean (Standard Deviation)
Unit of Measure: mmHg
0  (9) 1  (9)
5.Secondary Outcome
Title Change in Physical Functioning Score (Short Form 36 [SF-36])
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 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame Randomization (week 20) 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.
Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Overall Number of Participants Analyzed 515 245
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
Change in physical functioning score (SF-36) 1.0  (3.8) -1.2  (4.5)
Change in SF-36 role-physical score 0.3  (5.0) -0.9  (5.3)
Change in SF-36 bodily pain score 0.5  (7.0) -1.5  (7.7)
Change in SF-36 general health score 0.3  (5.2) -1.8  (5.8)
Change in SF-36 vitality score 1.1  (7.1) -2.1  (7.6)
Change in SF-36 social functioning score 0.1  (6.2) -1.8  (6.9)
Change in SF-36 mental health score 0.2  (6.2) -2.2  (7.6)
Change in SF-36 physical component summary 0.8  (4.9) -0.9  (5.6)
Change in SF-36 mental component summary 0.0  (6.2) -2.4  (8.5)
Change in SF-36 role-emotional score 0.0  (5.5) -2.2  (7.0)
6.Secondary Outcome
Title Change in Body Weight [Kilogram (Kg)]
Hide Description Change in body weight from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame Randomisation (week 20) 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.
Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Overall Number of Participants Analyzed 520 250
Mean (Standard Deviation)
Unit of Measure: Kg
-7.5  (7.6) 5.7  (6.7)
7.Secondary Outcome
Title Change in Body Mass Index (BMI)
Hide Description Change in BMI from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame Randomization (week 20) 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.
Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Overall Number of Participants Analyzed 520 250
Mean (Standard Deviation)
Unit of Measure: Kilogram per square meter (kg/sqm)
-2.7  (2.7) 2.0  (2.4)
8.Secondary Outcome
Title Change in Haemoglobin A1c (HbA1c) [%]
Hide Description Change in HbA1c from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame Randomization (week 20) 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.
Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Overall Number of Participants Analyzed 515 246
Mean (Standard Deviation)
Unit of Measure: Percentage point of HbA1c
-0.2  (0.3) 0.1  (0.2)
9.Secondary Outcome
Title Change in HbA1c [Millimoles Per Mole (mmol/Mol)]
Hide Description Change in HbA1c from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame Randomization (week 20) 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.
Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Overall Number of Participants Analyzed 515 246
Mean (Standard Deviation)
Unit of Measure: mmol/mol
-1.7  (2.8) 1.2  (2.7)
10.Secondary Outcome
Title Change in Fasting Plasma Glucose [Milligrams Per Deciliter (mg/dL)]
Hide Description Change in fasting plasma glucose from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame Randomization (week 20) 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.
Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Overall Number of Participants Analyzed 511 242
Mean (Standard Deviation)
Unit of Measure: mg/dL
-1.1  (8.6) 7.6  (10.0)
11.Secondary Outcome
Title Change in Fasting Plasma Glucose [Millimoles Per Litre (mmol/L)]
Hide Description Change in fasting plasma glucose from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame Randomization (week 20) 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.
Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Overall Number of Participants Analyzed 511 242
Mean (Standard Deviation)
Unit of Measure: mmol/L
-0.1  (0.5) 0.4  (0.6)
12.Secondary Outcome
Title Change in Fasting Serum Insulin
Hide Description Change in fasting serum insulin from baseline (week 20) 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame Randomization (week 20) 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.
Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Overall Number of Participants Analyzed 498 240
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio of fasting serum insulin
0.81
(60.9%)
1.03
(64.6%)
13.Secondary Outcome
Title Change in Total Cholesterol
Hide Description Change in fasting total cholesterol from baseline (week 20) to week 68 (measured as mmol/L) 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame Randomization (week 20) 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.
Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Overall Number of Participants Analyzed 517 245
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio of fasting total cholesterol
1.05
(13.5%)
1.11
(14.4%)
14.Secondary Outcome
Title Change in High-density Lipoproteins (HDL)
Hide Description Change in fasting HDL from baseline (week 20) to week 68 (measured as mmol/L) 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame Randomization (week 20) 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.
Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Overall Number of Participants Analyzed 515 245
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio of fasting HDL cholesterol
1.18
(13.2%)
1.18
(16.3%)
15.Secondary Outcome
Title Change in Low-density Lipoproteins (LDL)
Hide Description Change in fasting LDL from baseline (week 20) to week 68 (measured as mmol/L) 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame Randomization (week 20) 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.
Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Overall Number of Participants Analyzed 517 245
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio of fasting LDL cholesterol
1.01
(19.8%)
1.07
(21.3%)
16.Secondary Outcome
Title Change in Very Low-density Lipoproteins (VLDL)
Hide Description Change in fasting VLDL from baseline (week 20) to week 68 (measured as mmol/L) 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame Randomization (week 20) 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.
Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Overall Number of Participants Analyzed 517 245
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio of fasting VLDL
0.94
(33.6%)
1.12
(39.0%)
17.Secondary Outcome
Title Change in Free Fatty Acids
Hide Description Change in fasting free fatty acids from baseline (week 20) to week 68 (measured as mmol/L) 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame Randomization (week 20) 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.
Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Overall Number of Participants Analyzed 498 240
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio of fasting free fatty acids
0.78
(79.4%)
0.89
(73.1%)
18.Secondary Outcome
Title Change in Triglycerides
Hide Description Change in fasting triglycerides from baseline (week 20) to week 68 (measured as mmol/L) 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame Randomization (week 20) 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.
Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Overall Number of Participants Analyzed 517 245
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio of fasting triglycerides
0.94
(33.9%)
1.12
(39.4%)
19.Secondary Outcome
Title Subjects Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score
Hide Description The number of participants achieving at least a 4.3-point increase in SF-36 physical functioning score from baseline (week 20) to week 68 is presented. In the reported data, 'Yes' infers number of participants who have achieved 4.3 points of increase of the score and 'No' infers number of participants who have not achieved 4.3 points of increase of the score. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame Randomisation (week 20) 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.
Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Overall Number of Participants Analyzed 515 245
Measure Type: Count of Participants
Unit of Measure: Participants
Yes
58
  11.3%
11
   4.5%
No
457
  88.7%
234
  95.5%
20.Secondary Outcome
Title Subjects Who Gain Weight (Yes/no)
Hide Description The number of participants with weight gain from the start of the randomised period (week 20) to week 68 is presented. In the reported data, 'Yes' infers number of participants who have gained weight and 'No' infers number of participants who have not gained weight. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame Randomisation (week 20) 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.
Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Overall Number of Participants Analyzed 520 250
Measure Type: Count of Participants
Unit of Measure: Participants
Yes
79
  15.2%
206
  82.4%
No
441
  84.8%
44
  17.6%
21.Secondary Outcome
Title Change in Body Weight
Hide Description The body weight change (%) 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame Run-in (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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.
Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Overall Number of Participants Analyzed 520 250
Mean (Standard Deviation)
Unit of Measure: Percentage point
-17.7  (9.8) -5.4  (7.3)
22.Secondary Outcome
Title Subjects Who Achieve (Yes/no): Body Weight Reduction < 0%
Hide Description The number of participants who achieved less than (<) 0% weight loss from week 0 to week 68 is presented. In the reported data, 'Yes' infers number of participants who have achieved <0% weight loss whereas 'No' infers number of participants who have not achieved <0% 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame Run-in (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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.
Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Overall Number of Participants Analyzed 520 250
Measure Type: Count of Participants
Unit of Measure: Participants
Yes
22
   4.2%
51
  20.4%
No
498
  95.8%
199
  79.6%
23.Secondary Outcome
Title Subjects Who Achieve (Yes/no): Body Weight Reduction ≥ 5%
Hide Description The number of participants who achieved greater than or equal to (≥) 5% weight loss from week 0 to week 68 is presented. In the reported data, 'Yes' infers number of participants who have achieved ≥ 5% weight loss whereas 'No' infers number of participants who have not achieved ≥ 5% 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame Run-in (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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.
Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Overall Number of Participants Analyzed 520 250
Measure Type: Count of Participants
Unit of Measure: Participants
Yes
461
  88.7%
119
  47.6%
No
59
  11.3%
131
  52.4%
24.Secondary Outcome
Title Subjects Who Achieve (Yes/no): Body Weight Reduction ≥ 10%
Hide Description The number of participants who achieved ≥ 10% weight loss from week 0 to week 68 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame Run-in (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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.
Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Overall Number of Participants Analyzed 520 250
Measure Type: Count of Participants
Unit of Measure: Participants
Yes
411
  79.0%
51
  20.4%
No
109
  21.0%
199
  79.6%
25.Secondary Outcome
Title Subjects Who Achieve (Yes/no): Body Weight Reduction ≥ 15%
Hide Description The number of participants who achieved ≥ 15% weight loss from week 0 to week 68 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame Run-in (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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.
Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Overall Number of Participants Analyzed 520 250
Measure Type: Count of Participants
Unit of Measure: Participants
Yes
331
  63.7%
23
   9.2%
No
189
  36.3%
227
  90.8%
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 (week 0-20 run-in period). 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 Run-in (week 0) to randomisation (week 20)
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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.
Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Overall Number of Participants Analyzed 902 0
Measure Type: Number
Unit of Measure: Events
3775
27.Secondary Outcome
Title Number of Treatment-emergent AEs
Hide Description An 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 TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to treatment (week 20-75). 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 Randomisation (week 20) to week 75
Hide Outcome Measure Data
Hide Analysis Population Description
SAS included all participants who received at least one dose of trial product. Only randomised subjects in the safety analysis set contribute.
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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.
Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Overall Number of Participants Analyzed 535 268
Measure Type: Number
Unit of Measure: Events
1885 779
28.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 during run-in period from week 0 to week 20 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 Run-in (week 0) to randomisation (week 20)
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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.
Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Overall Number of Participants Analyzed 902 0
Measure Type: Number
Unit of Measure: Events
23
29.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 during run-in period from week 0 to week 20 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 Randomisation (week 20) to week 75
Hide Outcome Measure Data
Hide Analysis Population Description
SAS included all participants who received at least one dose of trial product. Only randomised subjects in the safety analysis set contribute.
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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.
Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Overall Number of Participants Analyzed 535 268
Measure Type: Number
Unit of Measure: Events
51 19
30.Secondary Outcome
Title Change in Pulse
Hide Description Change in pulse rate from week 0 week to week 20 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 Run-in (week 0) to randomisation (week 20)
Hide Outcome Measure Data
Hide Analysis Population Description
SAS included all participants who received at least one dose of trial product. Only randomised subjects in the safety analysis set contribute.
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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.
Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Overall Number of Participants Analyzed 535 268
Mean (Standard Deviation)
Unit of Measure: beats per minute (bpm)
5  (9) 5  (9)
31.Secondary Outcome
Title Change in Pulse
Hide Description Change in pulse from week 20 and 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 Randomisation (week 20) to week 68
Hide Outcome Measure Data
Hide Analysis Population Description
SAS included all participants who received at least one dose of trial product. Only randomised subjects in the safety analysis set contribute. '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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.
Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Overall Number of Participants Analyzed 495 234
Mean (Standard Deviation)
Unit of Measure: bpm
-2  (9) -5  (10)
32.Secondary Outcome
Title Change in Amylase
Hide Description Change in amylase (measured as units per liter [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 Run-in (week) 0 to randomization (week 20)
Hide Outcome Measure Data
Hide Analysis Population Description
SAS included all participants who received at least one dose of trial product. Only randomised subjects in the safety analysis set contribute.
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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.
Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Overall Number of Participants Analyzed 535 268
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio of amylase
1.06
(18.7%)
1.02
(26.2%)
33.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 Randomisation (week 20) to week 68
Hide Outcome Measure Data
Hide Analysis Population Description
SAS included all participants who received at least one dose of trial product. Only randomised subjects in the safety analysis set contribute. '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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.
Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Overall Number of Participants Analyzed 494 233
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio of amylase
1.06
(19.9%)
1.00
(24.9%)
34.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 Run-in (week 0) to randomization (week 20)
Hide Outcome Measure Data
Hide Analysis Population Description
SAS included all participants who received at least one dose of trial product. Only randomised subjects in the safety analysis set contribute.
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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.
Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Overall Number of Participants Analyzed 535 268
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio of lipase
1.44
(40.2%)
1.39
(53.5%)
35.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 Randomisation (week 20) to week 68
Hide Outcome Measure Data
Hide Analysis Population Description
SAS included all participants who received at least one dose of trial product. Only randomised subjects in the safety analysis set contribute. '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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.
Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Overall Number of Participants Analyzed 494 233
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ratio of lipase
0.94
(37.8%)
0.68
(51.7%)
36.Secondary Outcome
Title Change in Calcitonin
Hide Description Change in calcitonin (measured as nanogram per liter (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 Run-in (week 0) to randomization (week 20)
Hide Outcome Measure Data
Hide Analysis Population Description
SAS included all participants who received at least one dose of trial product. Only randomised subjects in the safety analysis set contribute.
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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.
Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Overall Number of Participants Analyzed 535 268
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio of Calcitonin
0.98
(28.4%)
0.96
(28.1%)
37.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 Randomisation (week 20) to week 68
Hide Outcome Measure Data
Hide Analysis Population Description
SAS included all participants who received at least one dose of trial product. Only randomised subjects in the safety analysis set contribute. '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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.
Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Overall Number of Participants Analyzed 491 233
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Ratio of Calcitonin
1.00
(24.8%)
0.95
(25.5%)
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: Run-in Period Semaglutide 2.4: Treatment Period Placebo: Treatment Period
Hide Arm/Group Description Participants were to receive once-weekly 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 in run-in period (week 0 to week 20) with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20. Thus, out of 803, 535 participants were continued to receive once weekly semaglutide s.c 2.4 mg until week 68. Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20. Thus, out of 803, 268 participants were switched to receive once weekly placebo until week 68.
All-Cause Mortality
Semaglutide: Run-in Period Semaglutide 2.4: Treatment Period Placebo: Treatment Period
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/902 (0.00%)      1/535 (0.19%)      1/268 (0.37%)    
Hide Serious Adverse Events
Semaglutide: Run-in Period Semaglutide 2.4: Treatment Period Placebo: Treatment Period
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   21/902 (2.33%)      41/535 (7.66%)      15/268 (5.60%)    
Blood and lymphatic system disorders       
Pancytopenia  1  0/902 (0.00%)  0 1/535 (0.19%)  1 0/268 (0.00%)  0
Cardiac disorders       
Acute myocardial infarction  1  2/902 (0.22%)  2 0/535 (0.00%)  0 1/268 (0.37%)  1
Atrial fibrillation  1  0/902 (0.00%)  0 1/535 (0.19%)  1 2/268 (0.75%)  2
Supraventricular tachycardia  1  0/902 (0.00%)  0 1/535 (0.19%)  1 0/268 (0.00%)  0
Ear and labyrinth disorders       
Vertigo  1  1/902 (0.11%)  1 1/535 (0.19%)  1 0/268 (0.00%)  0
Endocrine disorders       
Hypothyroidism  1  0/902 (0.00%)  0 1/535 (0.19%)  1 0/268 (0.00%)  0
Gastrointestinal disorders       
Abdominal pain  1  2/902 (0.22%)  2 1/535 (0.19%)  1 1/268 (0.37%)  1
Constipation  1  0/902 (0.00%)  0 0/535 (0.00%)  0 1/268 (0.37%)  1
Diverticular perforation  1  0/902 (0.00%)  0 0/535 (0.00%)  0 1/268 (0.37%)  1
Intestinal obstruction  1  0/902 (0.00%)  0 0/535 (0.00%)  0 1/268 (0.37%)  1
Nausea  1  0/902 (0.00%)  0 1/535 (0.19%)  1 0/268 (0.00%)  0
Vomiting  1  0/902 (0.00%)  0 1/535 (0.19%)  1 0/268 (0.00%)  0
General disorders       
Death  1  0/902 (0.00%)  0 1/535 (0.19%)  1 0/268 (0.00%)  0
Non-cardiac chest pain  1  0/902 (0.00%)  0 1/535 (0.19%)  1 0/268 (0.00%)  0
Hepatobiliary disorders       
Biliary cyst  1  1/902 (0.11%)  1 0/535 (0.00%)  0 0/268 (0.00%)  0
Cholecystitis  1  0/902 (0.00%)  0 1/535 (0.19%)  1 0/268 (0.00%)  0
Cholelithiasis  1  0/902 (0.00%)  0 5/535 (0.93%)  5 2/268 (0.75%)  2
Infections and infestations       
Abscess neck  1  1/902 (0.11%)  1 0/535 (0.00%)  0 0/268 (0.00%)  0
Appendicitis  1  0/902 (0.00%)  0 1/535 (0.19%)  1 1/268 (0.37%)  1
Cellulitis  1  1/902 (0.11%)  1 0/535 (0.00%)  0 0/268 (0.00%)  0
Diverticulitis  1  0/902 (0.00%)  0 1/535 (0.19%)  1 0/268 (0.00%)  0
Gastroenteritis  1  0/902 (0.00%)  0 2/535 (0.37%)  2 0/268 (0.00%)  0
Induced abortion infection  1  0/902 (0.00%)  0 0/535 (0.00%)  0 1/268 (0.37%)  1
Pertussis  1  0/902 (0.00%)  0 1/535 (0.19%)  1 0/268 (0.00%)  0
Pyelonephritis acute  1  0/902 (0.00%)  0 1/535 (0.19%)  1 0/268 (0.00%)  0
Tooth abscess  1  0/902 (0.00%)  0 0/535 (0.00%)  0 1/268 (0.37%)  1
Urinary tract infection  1  0/902 (0.00%)  0 0/535 (0.00%)  0 1/268 (0.37%)  1
Injury, poisoning and procedural complications       
Ankle fracture  1  0/902 (0.00%)  0 0/535 (0.00%)  0 1/268 (0.37%)  1
Arthropod bite  1  1/902 (0.11%)  1 0/535 (0.00%)  0 0/268 (0.00%)  0
Corneal abrasion  1  1/902 (0.11%)  1 0/535 (0.00%)  0 0/268 (0.00%)  0
Fall  1  0/902 (0.00%)  0 1/535 (0.19%)  1 0/268 (0.00%)  0
Incisional hernia  1  0/902 (0.00%)  0 1/535 (0.19%)  1 0/268 (0.00%)  0
Lower limb fracture  1  1/902 (0.11%)  1 0/535 (0.00%)  0 0/268 (0.00%)  0
Meniscus injury  1  0/902 (0.00%)  0 1/535 (0.19%)  1 1/268 (0.37%)  1
Post lumbar puncture syndrome  1  0/902 (0.00%)  0 1/535 (0.19%)  1 0/268 (0.00%)  0
Road traffic accident  1  0/902 (0.00%)  0 0/535 (0.00%)  0 1/268 (0.37%)  1
Spinal compression fracture  1  0/902 (0.00%)  0 1/535 (0.19%)  1 0/268 (0.00%)  0
Metabolism and nutrition disorders       
Dehydration  1  1/902 (0.11%)  1 0/535 (0.00%)  0 0/268 (0.00%)  0
Type 2 diabetes mellitus  1  0/902 (0.00%)  0 1/535 (0.19%)  1 0/268 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Intervertebral disc protrusion  1  0/902 (0.00%)  0 1/535 (0.19%)  1 0/268 (0.00%)  0
Osteoarthritis  1  3/902 (0.33%)  3 0/535 (0.00%)  0 0/268 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Endometrial adenocarcinoma  1  0/902 (0.00%)  0 1/535 (0.19%)  1 0/268 (0.00%)  0
Endometrial cancer stage II  1  1/902 (0.11%)  1 0/535 (0.00%)  0 0/268 (0.00%)  0
Haemangioma  1  0/902 (0.00%)  0 1/535 (0.19%)  1 0/268 (0.00%)  0
Intraductal proliferative breast lesion  1  0/902 (0.00%)  0 1/535 (0.19%)  1 0/268 (0.00%)  0
Invasive breast carcinoma  1  0/902 (0.00%)  0 1/535 (0.19%)  1 0/268 (0.00%)  0
Invasive ductal breast carcinoma  1  0/902 (0.00%)  0 1/535 (0.19%)  1 0/268 (0.00%)  0
Lung cancer metastatic  1  0/902 (0.00%)  0 0/535 (0.00%)  0 1/268 (0.37%)  1
Malignant melanoma  1  0/902 (0.00%)  0 1/535 (0.19%)  1 0/268 (0.00%)  0
Marginal zone lymphoma  1  0/902 (0.00%)  0 1/535 (0.19%)  1 0/268 (0.00%)  0
Uterine leiomyoma  1  0/902 (0.00%)  0 1/535 (0.19%)  1 0/268 (0.00%)  0
Nervous system disorders       
Carotid sinus syndrome  1  0/902 (0.00%)  0 0/535 (0.00%)  0 1/268 (0.37%)  1
Hemiparaesthesia  1  1/902 (0.11%)  1 0/535 (0.00%)  0 0/268 (0.00%)  0
Hemiparesis  1  0/902 (0.00%)  0 1/535 (0.19%)  1 0/268 (0.00%)  0
Migraine  1  0/902 (0.00%)  0 2/535 (0.37%)  2 0/268 (0.00%)  0
Paraesthesia  1  0/902 (0.00%)  0 1/535 (0.19%)  2 0/268 (0.00%)  0
Quadriplegia  1  0/902 (0.00%)  0 1/535 (0.19%)  1 0/268 (0.00%)  0
Syncope  1  1/902 (0.11%)  1 0/535 (0.00%)  0 0/268 (0.00%)  0
Transient global amnesia  1  0/902 (0.00%)  0 1/535 (0.19%)  1 0/268 (0.00%)  0
Pregnancy, puerperium and perinatal conditions       
Morning sickness  1  0/902 (0.00%)  0 1/535 (0.19%)  1 0/268 (0.00%)  0
Product Issues       
Lead dislodgement  1  0/902 (0.00%)  0 1/535 (0.19%)  1 0/268 (0.00%)  0
Renal and urinary disorders       
Nephrolithiasis  1  2/902 (0.22%)  2 1/535 (0.19%)  1 0/268 (0.00%)  0
Ureterolithiasis  1  0/902 (0.00%)  0 1/535 (0.19%)  1 0/268 (0.00%)  0
Reproductive system and breast disorders       
Menorrhagia  1  0/902 (0.00%)  0 0/535 (0.00%)  0 1/268 (0.37%)  1
Ovarian cyst  1  1/902 (0.11%)  1 0/535 (0.00%)  0 0/268 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Pulmonary embolism  1  1/902 (0.11%)  1 0/535 (0.00%)  0 0/268 (0.00%)  0
Surgical and medical procedures       
Arthroscopic surgery  1  1/902 (0.11%)  1 0/535 (0.00%)  0 0/268 (0.00%)  0
Orthognathic surgery  1  0/902 (0.00%)  0 1/535 (0.19%)  1 0/268 (0.00%)  0
Vascular disorders       
Hypertension  1  0/902 (0.00%)  0 1/535 (0.19%)  1 0/268 (0.00%)  0
Hypotension  1  0/902 (0.00%)  0 1/535 (0.19%)  1 0/268 (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: Run-in Period Semaglutide 2.4: Treatment Period Placebo: Treatment Period
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   670/902 (74.28%)      295/535 (55.14%)      114/268 (42.54%)    
Gastrointestinal disorders       
Abdominal distension  1  50/902 (5.54%)  53 8/535 (1.50%)  10 2/268 (0.75%)  2
Abdominal pain  1  67/902 (7.43%)  82 34/535 (6.36%)  45 8/268 (2.99%)  9
Abdominal pain upper  1  49/902 (5.43%)  64 20/535 (3.74%)  22 3/268 (1.12%)  3
Constipation  1  200/902 (22.17%)  232 62/535 (11.59%)  75 16/268 (5.97%)  18
Diarrhoea  1  212/902 (23.50%)  309 77/535 (14.39%)  114 19/268 (7.09%)  26
Dyspepsia  1  103/902 (11.42%)  127 9/535 (1.68%)  9 2/268 (0.75%)  2
Eructation  1  71/902 (7.87%)  88 14/535 (2.62%)  15 1/268 (0.37%)  1
Flatulence  1  50/902 (5.54%)  73 14/535 (2.62%)  44 3/268 (1.12%)  4
Gastrooesophageal reflux disease  1  58/902 (6.43%)  60 5/535 (0.93%)  6 1/268 (0.37%)  1
Nausea  1  422/902 (46.78%)  629 75/535 (14.02%)  104 13/268 (4.85%)  13
Vomiting  1  140/902 (15.52%)  239 54/535 (10.09%)  87 8/268 (2.99%)  13
General disorders       
Fatigue  1  67/902 (7.43%)  69 26/535 (4.86%)  29 6/268 (2.24%)  6
Infections and infestations       
Influenza  1  28/902 (3.10%)  28 39/535 (7.29%)  45 19/268 (7.09%)  23
Nasopharyngitis  1  92/902 (10.20%)  102 58/535 (10.84%)  77 39/268 (14.55%)  54
Metabolism and nutrition disorders       
Decreased appetite  1  102/902 (11.31%)  115 7/535 (1.31%)  7 0/268 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Arthralgia  1  21/902 (2.33%)  23 25/535 (4.67%)  28 14/268 (5.22%)  16
Back pain  1  26/902 (2.88%)  28 28/535 (5.23%)  32 18/268 (6.72%)  19
Nervous system disorders       
Headache  1  96/902 (10.64%)  119 41/535 (7.66%)  48 10/268 (3.73%)  10
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: NCT03548987    
Other Study ID Numbers: NN9536-4376
U1111-1201-0898 ( Other Identifier: World Health Organization (WHO) )
2017-003473-34 ( Registry Identifier: European Medicines Agency (EudraCT) )
First Submitted: May 25, 2018
First Posted: June 7, 2018
Results First Submitted: February 19, 2021
Results First Posted: March 15, 2021
Last Update Posted: March 15, 2021