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    Clinical Trial Results:
    Effect and safety of semaglutide 2.4 mg once-weekly in subjects with overweight or obesity and type 2 diabetes

    Summary
    EudraCT number
    		 2017-003414-10
    Trial protocol
    		 GB   DE   ES   GR  
    Global end of trial date
    01 May 2020

    Results information
    Results version number
    		 v2(current)
    This version publication date
    02 Jul 2021
    First version publication date
    15 May 2021
    Other versions
    		 v1
    Version creation reason

    Trial information

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    Trial identification
    Sponsor protocol code
    NN9536-4374
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03552757
    WHO universal trial number (UTN)
    		 U1111-1200-8148
    Other trial identifiers
    		 JapicCTI: 183992
    Sponsors
    Sponsor organisation name
    Novo Nordisk A/S
    Sponsor organisation address
    Novo Allé, Bagsværd, Denmark, 2880
    Public contact
    Clinical Transparency Anchor and Disclosure (1452), Novo Nordisk A/S, clinicaltrials@novonordisk.com
    Scientific contact
    Clinical Transparency Anchor and Disclosure (1452), Novo Nordisk A/S, clinicaltrials@novonordisk.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    28 Aug 2020
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    24 Mar 2020
    Global end of trial reached?
    Yes
    Global end of trial date
    01 May 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To compare the effect of semaglutide subcutaneous (s.c.; under the skin) 2.4 milligram (mg) once-weekly versus semaglutide placebo I/II as an adjunct to a reduced-calorie diet and increased physical activity in subjects with overweight or obesity and type 2 diabetes (T2D) on body weight.
    Protection of trial subjects
    The trial was conducted in accordance with the Declaration of Helsinki (2013) and International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice (2016) and 21 United States (US) Code of Federal Regulations (CFR) 312.120.
    Background therapy
    		 Not applicable
    Evidence for comparator
    		 Not applicable
    Actual start date of recruitment
    04 Jun 2018
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Arab Emirates: 38
    Country: Number of subjects enrolled
    Argentina: 62
    Country: Number of subjects enrolled
    Canada: 55
    Country: Number of subjects enrolled
    Germany: 70
    Country: Number of subjects enrolled
    Spain: 56
    Country: Number of subjects enrolled
    United Kingdom: 86
    Country: Number of subjects enrolled
    Greece: 47
    Country: Number of subjects enrolled
    India: 164
    Country: Number of subjects enrolled
    Japan: 125
    Country: Number of subjects enrolled
    Russian Federation: 96
    Country: Number of subjects enrolled
    United States: 361
    Country: Number of subjects enrolled
    South Africa: 50
    Worldwide total number of subjects
    1210
    EEA total number of subjects
    173
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    953
    From 65 to 84 years
    257
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 The trial was conducted at 149 sites in 12 countries as follows: Argentina (5 sites), Canada (10 sites), Germany (9 sites), Greece (6 sites), India (18 sites), Japan (12 sites), Russian Federation (9 sites), South Africa (6 sites), Spain (8 sites), United Arab Emirates (5 sites), United Kingdom (10 sites) and United States (51 sites).

    Pre-assignment
    Screening details
    		 Subjects were randomised in 1:1:1 ratio to receive either ‘semaglutide 2.4 milligram (mg) and placebo II (placebo matched to semaglutide 1.0 mg) once weekly’, ‘semaglutide 1.0 mg and placebo I (placebo matched to semaglutide 2.4 mg) once weekly’ or ‘placebo I and placebo II once weekly’.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator
    Blinding implementation details
    Semaglutide and placebo were identical in appearance and were packed and labelled to fulfil the requirements for double-blind procedures.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Semaglutide 1.0 mg
    Arm description
    		 Subjects received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Subjects also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Subjects received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Semaglutide B 1.34 mg/mL PDS290
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Dosing was done once weekly with dose escalation every fourth week until semaglutide 1.0 mg was reached. Semaglutide was administered using a PDS290 pre-filled pen-injector containing semaglutide 1.34 mg/mL. Injection was done once weekly at the same day of the week (to the extent possible). Injections were administered in the thigh, abdomen or upper arm, and at any time of the day irrespective of meals.

    Arm title
    		 Semaglutide 2.4 mg
    Arm description
    		 Subjects received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Subjects also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Subjects received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Semaglutide B 1.0 mg/mL PDS290
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Semaglutide 1.0 mg/mL was only dispensed at the first dispensing visit to cover the 0.25 and 0.5 mg dose escalation purposes. Semaglutide was administered using a PDS290 pre-filled pen-injector containing semaglutide 1.0 mg/mL. Injection was done once weekly at the same day of the week (to the extent possible). Injections were administered in the thigh, abdomen or upper arm, and at any time of the day irrespective of meals.

    Investigational medicinal product name
    Semaglutide B 3.0 mg/mL PDS290
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Dosing was done once weekly with dose escalation every fourth week until semaglutide 2.4 mg was reached. Semaglutide was administered using a PDS290 pre-filled pen-injector containing semaglutide 3.0 mg/mL. Injection was done once weekly at the same day of the week (to the extent possible). Injections were administered in the thigh, abdomen or upper arm, and at any time of the day irrespective of meals.

    Arm title
    		 Placebo
    Arm description
    		 Subjects received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Subjects received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo I
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Placebo I (placebo matched to semaglutide 2.4 mg) was administered using a PDS290 pre-filled pen-injector by subjects in both ‘semaglutide 1.0 mg’ and ‘placebo’ groups. Injection was done once weekly at the same day of the week (to the extent possible). Injections were administered in the thigh, abdomen or upper arm, and at any time of the day irrespective of meals.

    Investigational medicinal product name
    Placebo II
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Placebo II (placebo matched to semaglutide 1.0 mg) was administered using a PDS290 pre-filled pen-injector by subjects in both ‘semaglutide 2.4 mg’ and ‘placebo’ groups. Injection was done once weekly at the same day of the week (to the extent possible). Injections were administered in the thigh, abdomen or upper arm, and at any time of the day irrespective of meals.

    Number of subjects in period 1
    		Semaglutide 1.0 mg Semaglutide 2.4 mg Placebo
    Started
    403
    404
    403
    Exposed
    402
    403
    402
    Full analysis set (FAS)
    403
    404
    403
    Safety analysis set (SAS)
    402
    403
    402
    Completed
    390
    391
    383
    Not completed
    13
    13
    20
         Adverse event, serious fatal
    1
    1
    1
         Consent withdrawn by subject
    10
    5
    12
         Lost to follow-up
    2
    7
    7

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Semaglutide 1.0 mg
    Reporting group description
    		 Subjects received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Subjects also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Subjects received the treatments as an adjunct to a reduced calorie diet and increased physical activity.

    Reporting group title
    Semaglutide 2.4 mg
    Reporting group description
    		 Subjects received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Subjects also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Subjects received the treatments as an adjunct to a reduced calorie diet and increased physical activity.

    Reporting group title
    Placebo
    Reporting group description
    		 Subjects received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Subjects received the treatments as an adjunct to a reduced calorie diet and increased physical activity.

    Reporting group values
    		 Semaglutide 1.0 mg Semaglutide 2.4 mg Placebo Total
    Number of subjects
    		 403 404 403 1210
    Age Categorical
    Units: Subjects
        Adults (18-64 years)
    		 320 316 317 953
        From 65-84 years
    		 83 88 86 257
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 56 ± 10 55 ± 11 55 ± 11 -
    Gender Categorical
    Units: Subjects
        Female
    		 203 223 190 616
        Male
    		 200 181 213 594

    End points

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    End points reporting groups
    Reporting group title
    Semaglutide 1.0 mg
    Reporting group description
    		 Subjects received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Subjects also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Subjects received the treatments as an adjunct to a reduced calorie diet and increased physical activity.

    Reporting group title
    Semaglutide 2.4 mg
    Reporting group description
    		 Subjects received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Subjects also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Subjects received the treatments as an adjunct to a reduced calorie diet and increased physical activity.

    Reporting group title
    Placebo
    Reporting group description
    		 Subjects received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Subjects received the treatments as an adjunct to a reduced calorie diet and increased physical activity.

    Primary: Change in body weight (%) - semaglutide 2.4 mg versus placebo

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    End point title
    		 Change in body weight (%) - semaglutide 2.4 mg versus placebo [1]
    End point description
    Change in body weight (%) from baseline (week 0) to week 68 is presented. Results are based on the data from both in-trial and on-treatment observation periods. In-trial observation period: the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact (week 75). On-treatment observation period: the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 2-week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses. Number of subjects analysed = full analysis set (FAS) which comprised all randomised subjects. n = number of subjects with available data.
    End point type
    Primary
    End point timeframe
    From baseline (week 0) to week 68
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint compared 'Semaglutide 2.4 mg arm' with 'Placebo arm', thus values only for these two arms are provided.
    End point values
    		 Semaglutide 2.4 mg Placebo
    Number of subjects analysed
    404
    403
    Units: Percentage point of body weight
    arithmetic mean (standard deviation)
        In-trial observation period (n=388 & 376)
    -9.9 ± 8.0
    -3.3 ± 5.5
        On-treatment observation period (n=351 & 340)
    -10.7 ± 7.8
    -3.1 ± 5.2
    Statistical analysis title
    		 Semaglutide 2.4 mg versus Placebo
    Statistical analysis description
    Results are based on the data from in-trial observation period. Week 68 responses were analysed using an analysis of covariance model (ANCOVA) with randomised treatment, stratification groups (oral anti-diabetic (OAD) treatment status and HbA1c category at screening) and the interaction between stratification groups as factors and baseline body weight as covariate.
    Comparison groups
    Semaglutide 2.4 mg v Placebo
    Number of subjects included in analysis
    807
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [2]
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 Treatment difference
    Point estimate
    -6.21
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.28
         upper limit
    		 -5.15
    Notes
    [2] - ‘Number of subjects included in analysis’ is being erroneously displayed as 807. It should be read as “number of subjects with an observation at week 68 = 764”.
    Statistical analysis title
    		 Semaglutide 2.4 mg versus Placebo
    Statistical analysis description
    Results are based on the data from on-treatment observation period. All responses prior to first discontinuation of treatment (or initiation of other anti-obesity medication or bariatric surgery) were included in a mixed model for repeated measurements (MMRM) with randomised treatment, stratification groups (OAD treatment status and HbA1c category at screening) and the interaction between stratification groups as factors and baseline body weight as covariate, all nested within visit.
    Comparison groups
    Semaglutide 2.4 mg v Placebo
    Number of subjects included in analysis
    807
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [3]
    P-value
    		 < 0.0001
    Method
    		 MMRM
    Parameter type
    		 Treatment difference
    Point estimate
    -7.57
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.56
         upper limit
    		 -6.58
    Notes
    [3] - ‘Number of subjects included in analysis’ is being erroneously displayed as 807. It should be read as “number of subjects with an observation at week 68 = 633”.

    Primary: Subjects who achieve body weight reduction ≥5% from baseline (week 0) (yes/no) - semaglutide 2.4 mg versus placebo

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    End point title
    		 Subjects who achieve body weight reduction ≥5% from baseline (week 0) (yes/no) - semaglutide 2.4 mg versus placebo [4]
    End point description
    Number of subjects who achieved weight reduction ≥5% of their baseline body weight (yes/no) at week 68 is presented. Results are based on the data from both in-trial and on-treatment observation periods. In-trial observation period: the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. On-treatment observation period: the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 2 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses. Number of subjects analysed = FAS which comprised all randomised subjects. n = number of subjects with available data.
    End point type
    Primary
    End point timeframe
    After 68 weeks
    Notes
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint compared 'Semaglutide 2.4 mg arm' with 'Placebo arm', thus values only for these two arms are provided.
    End point values
    		 Semaglutide 2.4 mg Placebo
    Number of subjects analysed
    404
    403
    Units: Subjects
        In-trial observation period (n=388 & 376): Yes
    267
    107
        In-trial observation period (n=388 & 376): No
    121
    269
        On-treatment observation period (n=351 & 340): Yes
    257
    94
        On-treatment observation period (n=351 & 340): No
    94
    246
    Statistical analysis title
    		 Semaglutide 2.4 mg versus Placebo
    Statistical analysis description
    Results are based on the data from in-trial observation period. Week 68 responses were analysed using a binary logistic regression model with randomised treatment, stratification groups (OAD treatment status and HbA1c category at screening) and the interaction between stratification groups as factors and baseline body weight as covariate.
    Comparison groups
    Semaglutide 2.4 mg v Placebo
    Number of subjects included in analysis
    807
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [5]
    P-value
    		 < 0.0001
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    4.88
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.58
         upper limit
    		 6.64
    Notes
    [5] - ‘Number of subjects included in analysis’ is being erroneously displayed as 807. It should be read as “number of subjects with an observation at week 68 = 764”.
    Statistical analysis title
    		 Semaglutide 2.4 mg versus Placebo
    Statistical analysis description
    Results are based on the data from on-treatment observation period. All responses prior to first discontinuation of treatment (or initiation of other anti-obesity medication or bariatric surgery) were included in a MMRM with randomised treatment, stratification groups (OAD treatment status and HbA1c category at screening) and the interaction between stratification groups as factors and baseline body weight as covariate, all nested within visit.
    Comparison groups
    Semaglutide 2.4 mg v Placebo
    Number of subjects included in analysis
    807
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [6]
    P-value
    		 < 0.0001
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    8.69
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 6.31
         upper limit
    		 11.97
    Notes
    [6] - ‘Number of subjects included in analysis’ is being erroneously displayed as 807. It should be read as “number of subjects with an observation at week 68 = 633”.

    Secondary: Change in body weight (%) - semaglutide 2.4 mg versus semaglutide 1.0 mg

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    End point title
    		 Change in body weight (%) - semaglutide 2.4 mg versus semaglutide 1.0 mg [7]
    End point description
    Change in body weight (%) from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. This endpoint was evaluated based on the FAS which comprised all randomised subjects. Number of subjects analysed = number of subjects with available data.
    End point type
    Secondary
    End point timeframe
    From baseline (week 0) to week 68
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint compared 'Semaglutide 2.4 mg arm' with 'Placebo arm', thus values only for these two arms are provided.
    End point values
    		 Semaglutide 1.0 mg Semaglutide 2.4 mg
    Number of subjects analysed
    380
    388
    Units: Percentage point of body weight
        arithmetic mean (standard deviation)
    -7.2 ± 6.6
    -9.9 ± 8.0
    No statistical analyses for this end point

    Secondary: Subjects who achieve (yes/no): Body weight reduction ≥10% from baseline (week 0)

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    End point title
    		 Subjects who achieve (yes/no): Body weight reduction ≥10% from baseline (week 0)
    End point description
    Number of subjects who achieved weight reduction ≥10% of their baseline body weight (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. This endpoint was evaluated based on the FAS which comprised all randomised subjects. Number of subjects analysed = number of subjects with available data.
    End point type
    Secondary
    End point timeframe
    After 68 weeks
    End point values
    		 Semaglutide 1.0 mg Semaglutide 2.4 mg Placebo
    Number of subjects analysed
    380
    388
    376
    Units: Subjects
        Yes
    109
    177
    31
        No
    271
    211
    345
    No statistical analyses for this end point

    Secondary: Subjects who achieve (yes/no): Body weight reduction ≥15% from baseline (week 0)

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    End point title
    		 Subjects who achieve (yes/no): Body weight reduction ≥15% from baseline (week 0)
    End point description
    Number of subjects who achieved weight reduction ≥15% of their baseline body weight (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. This endpoint was evaluated based on the FAS which comprised all randomised subjects. Number of subjects analysed = number of subjects with available data.
    End point type
    Secondary
    End point timeframe
    After 68 weeks
    End point values
    		 Semaglutide 1.0 mg Semaglutide 2.4 mg Placebo
    Number of subjects analysed
    380
    388
    376
    Units: Subjects
        Yes
    52
    100
    12
        No
    328
    288
    364
    No statistical analyses for this end point

    Secondary: Change in waist circumference (cm)

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    End point title
    		 Change in waist circumference (cm)
    End point description
    Change in waist circumference from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. This endpoint was evaluated based on the FAS which comprised all randomised subjects. Number of subjects analysed = number of subjects with available data.
    End point type
    Secondary
    End point timeframe
    From baseline (week 0) to week 68
    End point values
    		 Semaglutide 1.0 mg Semaglutide 2.4 mg Placebo
    Number of subjects analysed
    380
    387
    375
    Units: Centimetre (cm)
        arithmetic mean (standard deviation)
    -6.9 ± 6.8
    -9.7 ± 8.1
    -4.3 ± 6.5
    No statistical analyses for this end point

    Secondary: Change in HbA1c (%)

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    End point title
    		 Change in HbA1c (%)
    End point description
    Change in glycated haemoglobin (HbA1c (%)) from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. This endpoint was evaluated based on the FAS which comprised all randomised subjects. Number of subjects analysed = number of subjects with available data.
    End point type
    Secondary
    End point timeframe
    From baseline (week 0) to week 68
    End point values
    		 Semaglutide 1.0 mg Semaglutide 2.4 mg Placebo
    Number of subjects analysed
    376
    381
    374
    Units: Percentage point of HbA1c
        arithmetic mean (standard deviation)
    -1.5 ± 1.1
    -1.7 ± 1.2
    -0.3 ± 1.3
    No statistical analyses for this end point

    Secondary: Change in HbA1c (mmol/mol)

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    End point title
    		 Change in HbA1c (mmol/mol)
    End point description
    Change in HbA1c (mmol/mol) from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. This endpoint was evaluated based on the FAS which comprised all randomised subjects. Number of subjects analysed = number of subjects with available data.
    End point type
    Secondary
    End point timeframe
    From baseline (week 0) to week 68
    End point values
    		 Semaglutide 1.0 mg Semaglutide 2.4 mg Placebo
    Number of subjects analysed
    376
    381
    374
    Units: millimoles per mole (mmol/mol)
        arithmetic mean (standard deviation)
    -16.9 ± 12.3
    -18.7 ± 13.0
    -3.4 ± 14.3
    No statistical analyses for this end point

    Secondary: Change in Systolic blood pressure (mmHg)

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    End point title
    		 Change in Systolic blood pressure (mmHg)
    End point description
    Change in systolic blood pressure from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. This endpoint was evaluated based on the FAS which comprised all randomised subjects. Number of subjects analysed = number of subjects with available data.
    End point type
    Secondary
    End point timeframe
    From baseline (week 0) to week 68
    End point values
    		 Semaglutide 1.0 mg Semaglutide 2.4 mg Placebo
    Number of subjects analysed
    379
    387
    376
    Units: Millimetre of mercury (mmHg)
        arithmetic mean (standard deviation)
    -3 ± 15
    -4 ± 14
    0 ± 15
    No statistical analyses for this end point

    Secondary: Change in diastolic blood pressure (mmHg)

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    End point title
    		 Change in diastolic blood pressure (mmHg)
    End point description
    Change in diastolic blood pressure from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. This endpoint was evaluated based on the FAS which comprised all randomised subjects. Number of subjects analysed = number of subjects with available data.
    End point type
    Secondary
    End point timeframe
    From baseline (week 0) to week 68
    End point values
    		 Semaglutide 1.0 mg Semaglutide 2.4 mg Placebo
    Number of subjects analysed
    379
    387
    376
    Units: Millimetre of mercury (mmHg)
        arithmetic mean (standard deviation)
    -1 ± 9
    -2 ± 9
    -1 ± 9
    No statistical analyses for this end point

    Secondary: Change in body weight (kg)

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    End point title
    		 Change in body weight (kg)
    End point description
    Change in body weight (kg) from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. This endpoint was evaluated based on the FAS which comprised all randomised subjects. Number of subjects analysed = number of subjects with available data.
    End point type
    Secondary
    End point timeframe
    From baseline (week 0) to week 68
    End point values
    		 Semaglutide 1.0 mg Semaglutide 2.4 mg Placebo
    Number of subjects analysed
    380
    388
    376
    Units: Kilogram (kg)
        arithmetic mean (standard deviation)
    -7.1 ± 6.7
    -9.9 ± 8.5
    -3.4 ± 6.2
    No statistical analyses for this end point

    Secondary: Change in BMI (kg/sqm)

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    End point title
    		 Change in BMI (kg/sqm)
    End point description
    Change in body mass index (BMI) from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. This endpoint was evaluated based on the FAS which comprised all randomised subjects. Number of subjects analysed = number of subjects with available data.
    End point type
    Secondary
    End point timeframe
    From baseline (week 0) to week 68
    End point values
    		 Semaglutide 1.0 mg Semaglutide 2.4 mg Placebo
    Number of subjects analysed
    380
    388
    376
    Units: kilogram per square meter (kg/m^2)
        arithmetic mean (standard deviation)
    -2.6 ± 2.4
    -3.6 ± 3.1
    -1.2 ± 2.1
    No statistical analyses for this end point

    Secondary: Change in fasting plasma glucose (FPG) (mg/dL)

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    End point title
    		 Change in fasting plasma glucose (FPG) (mg/dL)
    End point description
    Change in fasting plasma glucose (FPG) from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. This endpoint was evaluated based on the FAS which comprised all randomised subjects. Number of subjects analysed = number of subjects with available data.
    End point type
    Secondary
    End point timeframe
    From baseline (week 0) to week 68
    End point values
    		 Semaglutide 1.0 mg Semaglutide 2.4 mg Placebo
    Number of subjects analysed
    367
    375
    370
    Units: milligrams per deciliter (mg/dL)
        arithmetic mean (standard deviation)
    -36.5 ± 45.1
    -37.9 ± 45.9
    -2.3 ± 53.1
    No statistical analyses for this end point

    Secondary: Change in fasting serum insulin (mIU/L)

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    End point title
    		 Change in fasting serum insulin (mIU/L)
    End point description
    Change in fasting serum insulin from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. This endpoint was evaluated based on the FAS which comprised all randomised subjects. Number of subjects analysed = number of subjects with available data.
    End point type
    Secondary
    End point timeframe
    From baseline (week 0) to week 68
    End point values
    		 Semaglutide 1.0 mg Semaglutide 2.4 mg Placebo
    Number of subjects analysed
    352
    360
    351
    Units: Picomoles per litre (pmol/L)
        arithmetic mean (standard deviation)
    0.94 ± 59.8
    0.90 ± 65.4
    0.93 ± 53.6
    No statistical analyses for this end point

    Secondary: Change in total cholesterol (mg/dL)

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    End point title
    		 Change in total cholesterol (mg/dL)
    End point description
    Change in total cholesterol (measured in milligram per decilitre (mg/dL)) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. This endpoint was evaluated based on the FAS which comprised all randomised subjects. Number of subjects analysed = number of subjects with available data.
    End point type
    Secondary
    End point timeframe
    From baseline (week 0) to week 68
    End point values
    		 Semaglutide 1.0 mg Semaglutide 2.4 mg Placebo
    Number of subjects analysed
    372
    380
    373
    Units: Ratio of total cholesterol
        geometric mean (geometric coefficient of variation)
    0.97 ± 20.1
    0.99 ± 17.9
    1.00 ± 18.9
    No statistical analyses for this end point

    Secondary: Change in high density lipoprotein (HDL) cholesterol (mg/dL)

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    End point title
    		 Change in high density lipoprotein (HDL) cholesterol (mg/dL)
    End point description
    Change in high density lipoprotein (HDL; measured in mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. This endpoint was evaluated based on the FAS which comprised all randomised subjects. Number of subjects analysed = number of subjects with available data.
    End point type
    Secondary
    End point timeframe
    From baseline (week 0) to week 68
    End point values
    		 Semaglutide 1.0 mg Semaglutide 2.4 mg Placebo
    Number of subjects analysed
    372
    375
    369
    Units: Ratio of HDL cholesterol
        geometric mean (geometric coefficient of variation)
    1.06 ± 16.0
    1.07 ± 15.7
    1.04 ± 15.3
    No statistical analyses for this end point

    Secondary: Change in low density lipoprotein (LDL) cholesterol (mg/dL)

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    End point title
    		 Change in low density lipoprotein (LDL) cholesterol (mg/dL)
    End point description
    Change in low density lipoprotein (LDL; measured in mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. This endpoint was evaluated based on the FAS which comprised all randomised subjects. Number of subjects analysed = number of subjects with available data.
    End point type
    Secondary
    End point timeframe
    From baseline (week 0) to week 68
    End point values
    		 Semaglutide 1.0 mg Semaglutide 2.4 mg Placebo
    Number of subjects analysed
    372
    380
    373
    Units: Ratio of LDL cholesterol
        geometric mean (geometric coefficient of variation)
    0.99 ± 37.5
    1.00 ± 30.9
    1.00 ± 28.9
    No statistical analyses for this end point

    Secondary: Change in very low density lipoprotein (VLDL) cholesterol (mg/dL)

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    End point title
    		 Change in very low density lipoprotein (VLDL) cholesterol (mg/dL)
    End point description
    Change in very low density lipoprotein (VLDL; measured in mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. This endpoint was evaluated based on the FAS which comprised all randomised subjects. Number of subjects analysed = number of subjects with available data.
    End point type
    Secondary
    End point timeframe
    From baseline (week 0) to week 68
    End point values
    		 Semaglutide 1.0 mg Semaglutide 2.4 mg Placebo
    Number of subjects analysed
    372
    380
    373
    Units: Ratio of VLDL cholesterol
        geometric mean (geometric coefficient of variation)
    0.82 ± 42.1
    0.80 ± 42.0
    0.92 ± 40.5
    No statistical analyses for this end point

    Secondary: Change in free fatty acids (FFA)

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    End point title
    		 Change in free fatty acids (FFA)
    End point description
    Change in free fatty acids (measured in mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. This endpoint was evaluated based on the FAS which comprised all randomised subjects. Number of subjects analysed = number of subjects with available data.
    End point type
    Secondary
    End point timeframe
    From baseline (week 0) to week 68
    End point values
    		 Semaglutide 1.0 mg Semaglutide 2.4 mg Placebo
    Number of subjects analysed
    353
    361
    354
    Units: Ratio of free fatty acids
        geometric mean (geometric coefficient of variation)
    0.85 ± 61.4
    0.84 ± 68.7
    1.01 ± 62.3
    No statistical analyses for this end point

    Secondary: Change in triglycerides

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    End point title
    		 Change in triglycerides
    End point description
    Change in triglycerides (measured in mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. This endpoint was evaluated based on the FAS which comprised all randomised subjects. Number of subjects analysed = number of subjects with available data.
    End point type
    Secondary
    End point timeframe
    From baseline (week 0) to week 68
    End point values
    		 Semaglutide 1.0 mg Semaglutide 2.4 mg Placebo
    Number of subjects analysed
    372
    380
    373
    Units: Ratio of triglycerides
        geometric mean (geometric coefficient of variation)
    0.81 ± 44.5
    0.79 ± 43.8
    0.92 ± 44.5
    No statistical analyses for this end point

    Secondary: Change in high sensitivity C-Reactive Protein (hsCRP) (mg/L)

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    End point title
    		 Change in high sensitivity C-Reactive Protein (hsCRP) (mg/L)
    End point description
    Change in high sensitivity C-reactive protein (hsCRP; measured in milligram per ilitre (mg/L)) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. This endpoint was evaluated based on the FAS which comprised all randomised subjects. Number of subjects analysed = number of subjects with available data.
    End point type
    Secondary
    End point timeframe
    From baseline (week 0) to week 68
    End point values
    		 Semaglutide 1.0 mg Semaglutide 2.4 mg Placebo
    Number of subjects analysed
    372
    380
    373
    Units: Ratio of hsCRP
        geometric mean (geometric coefficient of variation)
    0.59 ± 115.7
    0.50 ± 125.7
    0.84 ± 90.9
    No statistical analyses for this end point

    Secondary: Plasminogen Activator Inhibitor-1 (PAI-1) Activity (AU/mL)

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    End point title
    		 Plasminogen Activator Inhibitor-1 (PAI-1) Activity (AU/mL)
    End point description
    Change in Plasminogen Activator Inhibitor-1 (PAI-1; measured in arbritary units per millilitre (AU/mL)) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. This endpoint was evaluated based on the FAS which comprised all randomised subjects. Number of subjects analysed = number of subjects with available data.
    End point type
    Secondary
    End point timeframe
    From baseline (week 0) to week 68
    End point values
    		 Semaglutide 1.0 mg Semaglutide 2.4 mg Placebo
    Number of subjects analysed
    334
    353
    336
    Units: Ratio of PAI-1 activity
        geometric mean (geometric coefficient of variation)
    1.21 ± 73.7
    1.06 ± 80.8
    1.42 ± 68.9
    No statistical analyses for this end point

    Secondary: Change in Short Form 36 v2.0 acute (SF-36) (physical functioning score)

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    End point title
    		 Change in Short Form 36 v2.0 acute (SF-36) (physical functioning score)
    End point description
    SF-36 is a 36-item patient-reported survey of patient health that measures the subject's overall health-related quality of life (HRQoL). SF-36v2™ questionnaire measured 8 domains of functional health and well-being as well as 2 component summary scores (physical component summary and mental component summary). This endpoint shows results for ‘physical functioning domain’. The 0-100 scale scores from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. In the metric of norm-based scores, 50 and 10 corresponds to the mean and standard deviation respectively. Change from week 0 in the domain scores were evaluated at week 68. A positive change score indicates an improvement since baseline. Results are based on the data from in-trial observation period. This endpoint was evaluated based on the FAS. Number of subjects analysed = number of subjects with available data.
    End point type
    Secondary
    End point timeframe
    Baseline (week 0) to week 68
    End point values
    		 Semaglutide 1.0 mg Semaglutide 2.4 mg Placebo
    Number of subjects analysed
    370
    376
    365
    Units: Score on a scale
        arithmetic mean (standard deviation)
    2.1 ± 6.8
    2.8 ± 7.7
    0.8 ± 7.0
    No statistical analyses for this end point

    Secondary: Change in SF-36 (all scores except physical functioning)

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    End point title
    		 Change in SF-36 (all scores except physical functioning)
    End point description
    SF-36 is a 36-item patient-reported survey of patient health that measures the subject's overall health-related quality of life (HRQoL). SF-36v2™ questionnaire measured 8 domains of functional health and well-being as well as 2 component summary scores (physical component summary & mental component summary). This endpoint shows results for all the domains, except physical functioning. The 0-100 scale scores from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. In the metric of norm-based scores, 50 and 10 corresponds to the mean and standard deviation respectively. Change from week 0 in the domain scores and component summary scores were evaluated at week 68. A positive change score indicates an improvement since baseline. Results are based on data from in-trial observation period. Analysis population=FAS. No. of subjects analysed=No. of subjects with available data.
    End point type
    Secondary
    End point timeframe
    From baseline (week 0) to week 68
    End point values
    		 Semaglutide 1.0 mg Semaglutide 2.4 mg Placebo
    Number of subjects analysed
    370
    376
    365
    Units: Score on a scale
    arithmetic mean (standard deviation)
        Role-Physical
    0.6 ± 6.9
    0.8 ± 7.4
    0.0 ± 7.1
        Bodily Pain
    0.4 ± 8.3
    0.3 ± 9.0
    -0.4 ± 8.6
        General Health
    1.7 ± 7.2
    2.2 ± 7.3
    0.6 ± 7.5
        Vitality
    -0.1 ± 7.8
    0.8 ± 7.9
    -0.9 ± 7.9
        Social Functioning
    -0.3 ± 6.6
    0.2 ± 6.6
    -0.7 ± 7.4
        Role-Emotional
    -0.4 ± 7.3
    -0.4 ± 7.7
    -1.1 ± 7.8
        Mental Health
    -0.9 ± 7.5
    -0.4 ± 6.9
    -1.6 ± 7.5
        Physical component summary
    1.9 ± 6.4
    2.3 ± 7.2
    0.9 ± 6.6
        Mental component summary
    -1.4 ± 7.4
    -0.9 ± 6.9
    -1.8 ± 7.6
    No statistical analyses for this end point

    Secondary: Change in IWQOL-Lite for CT (physical function domain (5-items) score)

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    End point title
    		 Change in IWQOL-Lite for CT (physical function domain (5-items) score)
    End point description
    The Impact of Weight on Quality of Life Clinical Trials Version (IWQOL-Lite-CT) is designed to assess the impact of changes in weight on patients' quality of life within the context of clinical trials. IWQOL-Lite-CT is a 20-item questionnaire-based instrument used to assess the impact of body weight changes on subject’s overall health-related quality of life (HRQoL). All IWQOL-Lite-CT composite scores range from 0 to 100, with higher scores reflecting better levels of functioning. This endpoint shows results for ‘physical function domain’. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. This endpoint was evaluated based on the FAS which comprised all randomised subjects. Number of subjects analysed = number of subjects with available data.
    End point type
    Secondary
    End point timeframe
    From baseline (week 0) to week 68
    End point values
    		 Semaglutide 1.0 mg Semaglutide 2.4 mg Placebo
    Number of subjects analysed
    369
    376
    365
    Units: Score on a scale
        arithmetic mean (standard deviation)
    8.5 ± 18.8
    11.4 ± 20.8
    4.9 ± 20.4
    No statistical analyses for this end point

    Secondary: Change in IWQOL-Lite for CT (all scores except physical function)

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    End point title
    		 Change in IWQOL-Lite for CT (all scores except physical function)
    End point description
    The Impact of Weight on Quality of Life Clinical Trials Version (IWQOL-Lite-CT) is designed to assess the impact of changes in weight on patients' quality of life within the context of clinical trials. IWQOL-Lite-CT is a 20-item questionnaire-based instrument used to assess the impact of body weight changes on subject’s overall health-related quality of life (HRQoL). All IWQOL-Lite-CT composite scores range from 0 to 100, with higher scores reflecting better levels of functioning. This endpoint shows results for ‘physical and psychosocial domains, and for total’. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. This endpoint was evaluated based on the FAS which comprised all randomised subjects. Number of subjects analysed = number of subjects with available data.
    End point type
    Secondary
    End point timeframe
    From baseline (week 0) to week 68
    End point values
    		 Semaglutide 1.0 mg Semaglutide 2.4 mg Placebo
    Number of subjects analysed
    369
    376
    365
    Units: Score on a scale
    arithmetic mean (standard deviation)
        Physical
    7.6 ± 18.0
    11.0 ± 19.6
    4.4 ± 19.1
        Psychosocial
    8.6 ± 15.7
    9.6 ± 16.7
    5.6 ± 16.5
        Total
    8.2 ± 14.8
    10.1 ± 15.9
    5.2 ± 15.5
    No statistical analyses for this end point

    Secondary: Subjects who achieve (yes/no): Responder definition value for SF-36 physical functioning score

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    End point title
    		 Subjects who achieve (yes/no): Responder definition value for SF-36 physical functioning score
    End point description
    Number of subjects experiencing a meaningful within subject improvement in SF-36 Physical function after 68 weeks was determined by two thresholds. The default generic responder threshold of 4.3 is for general population. The threshold of 3.7 is for overweight/obese population in the study and calculated using patient global rating anchor questionnaires to reflect subjects’ own perspective based on Food and Drug Administration (FDA) recommendations. In the reported data, number of subjects who have achieved an improvement in score >/= to threshold are inferred as “Yes” and who have not achieved an improvement in score >/= to threshold are inferred as “No”. The endpoint was evaluated based on in-trial observation period which is the uninterrupted time interval from randomization (week 0) to last trial related subject-site contact. The endpoint was evaluated based on the FAS which comprised all randomised subjects. Number of subjects analysed = number of subjects with available data.
    End point type
    Secondary
    End point timeframe
    After 68 weeks
    End point values
    		 Semaglutide 1.0 mg Semaglutide 2.4 mg Placebo
    Number of subjects analysed
    370
    376
    365
    Units: Subjects
        Yes (with threshold 4.3)
    88
    111
    68
        No (with threshold 4.3)
    282
    265
    297
        Yes (with threshold 3.7)
    130
    158
    102
        No (with threshold 3.7)
    240
    218
    263
    No statistical analyses for this end point

    Secondary: Subjects who achieve (yes/no): Responder definition value for IWQOL-Lite for CT physical function domain (5-items) score

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    End point title
    		 Subjects who achieve (yes/no): Responder definition value for IWQOL-Lite for CT physical function domain (5-items) score
    End point description
    Number of subjects experiencing a meaningful within subject improvement in IWQOL-Lite-CT physical function after 68 weeks was determined by two thresholds. The preliminary responder threshold 20 was based on earlier studies. The threshold of 14.6 is for the overweight/obese population in the study and calculated using patient global rating anchor questionnaires to reflect subjects’ own perspective based on FDA recommendations. In the reported data, number of subjects who have achieved an improvement in score >/= to threshold are inferred as “Yes” and who have not achieved an improvement in score >/= to threshold are inferred as “No”. The endpoint was evaluated based on in-trial observation period which was the uninterrupted time interval from randomization (week 0) to last trial related subject-site contact. The endpoint was evaluated based on the FAS which comprised all randomised subjects. Number of subjects analysed = number of subjects with available data.
    End point type
    Secondary
    End point timeframe
    After 68 weeks
    End point values
    		 Semaglutide 1.0 mg Semaglutide 2.4 mg Placebo
    Number of subjects analysed
    369
    376
    365
    Units: Subjects
    number (not applicable)
        Yes (with threshold 20)
    107
    131
    83
        No (with threshold 20)
    262
    245
    282
        Yes (with threshold 14.6)
    144
    160
    113
        No (with threshold 14.6)
    225
    216
    252
    No statistical analyses for this end point

    Secondary: Subjects who achieve (yes/no): HbA1c <7.0% (53 mmol/mol)

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    End point title
    		 Subjects who achieve (yes/no): HbA1c <7.0% (53 mmol/mol)
    End point description
    Number of subjects who achieved HbA1c <7% (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. This endpoint was evaluated based on the FAS which comprised all randomised subjects. Number of subjects analysed = number of subjects with available data.
    End point type
    Secondary
    End point timeframe
    After 68 weeks
    End point values
    		 Semaglutide 1.0 mg Semaglutide 2.4 mg Placebo
    Number of subjects analysed
    376
    381
    374
    Units: Subjects
    number (not applicable)
        Yes
    272
    299
    99
        No
    104
    82
    275
    No statistical analyses for this end point

    Secondary: Subjects who achieve (yes/no): HbA1c ≤6.5% (48 mmol/mol)

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    End point title
    		 Subjects who achieve (yes/no): HbA1c ≤6.5% (48 mmol/mol)
    End point description
    Number of subjects who achieved HbA1c ≤6.5% (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. This endpoint was evaluated based on the FAS which comprised all randomised subjects. Number of subjects analysed = number of subjects with available data.
    End point type
    Secondary
    End point timeframe
    After 68 weeks
    End point values
    		 Semaglutide 1.0 mg Semaglutide 2.4 mg Placebo
    Number of subjects analysed
    376
    381
    374
    Units: Subjects
        Yes
    226
    257
    58
        No
    150
    124
    316
    No statistical analyses for this end point

    Secondary: Number of treatment-emergent adverse events (TEAEs) - semaglutide 2.4 mg versus placebo

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    End point title
    		 Number of treatment-emergent adverse events (TEAEs) - semaglutide 2.4 mg versus placebo [8]
    End point description
    Adverse events (AEs) with onset during the on-treatment observation period were defined as treatment-emergent AEs (TEAEs). On-treatment observation period: the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 7 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least seven consecutive missed doses. This endpoint was evaluated based on the SAS which included all randomised subjects exposed to at least one dose of randomised treatment. Number of subjects analysed = number of subjects with available data.
    End point type
    Secondary
    End point timeframe
    From baseline (week 0) to week 75
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint compared 'Semaglutide 2.4 mg arm' with 'Placebo arm', thus values only for these two arms are provided.
    End point values
    		 Semaglutide 2.4 mg Placebo
    Number of subjects analysed
    403
    402
    Units: Events
    2197
    1388
    No statistical analyses for this end point

    Secondary: Number of serious adverse events (SAEs) - semaglutide 2.4 mg versus placebo

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    End point title
    		 Number of serious adverse events (SAEs) - semaglutide 2.4 mg versus placebo [9]
    End point description
    Serious adverse event (SAE) results are based on the on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 7 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least seven consecutive missed doses. This endpoint was evaluated based on the SAS which included all randomised subjects exposed to at least one dose of randomised treatment. Number of subjects analysed = number of subjects with available data.
    End point type
    Secondary
    End point timeframe
    From baseline (week 0) to week 75
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint compared 'Semaglutide 2.4 mg arm' with 'Placebo arm', thus values only for these two arms are provided.
    End point values
    		 Semaglutide 2.4 mg Placebo
    Number of subjects analysed
    403
    402
    Units: Events
    71
    53
    No statistical analyses for this end point

    Secondary: Number of treatment emergent severe or blood glucose confirmed symptomatic hypoglycaemia episodes - semaglutide 2.4 mg versus placebo

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    End point title
    		 Number of treatment emergent severe or blood glucose confirmed symptomatic hypoglycaemia episodes - semaglutide 2.4 mg versus placebo [10]
    End point description
    Hypoglycaemic episodes with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 7 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least 7 consecutive missed doses. Severe hypoglycaemia: An episode requiring assistance of another person to actively administer carbohydrate, glucagon or take other corrective actions. plasma glucose (PG) concentrations may not be available during an event, but neurological recovery following the return of PG to normal is considered sufficient evidence that the event was induced by a low PG concentration. Blood glucose (BG) confirmed symptomatic hypoglycaemia: An episode that is BG confirmed by PG value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.
    End point type
    Secondary
    End point timeframe
    From baseline (week 0) to week 75
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint compared 'Semaglutide 2.4 mg arm' with 'Placebo arm', thus values only for these two arms are provided.
    End point values
    		 Semaglutide 2.4 mg Placebo
    Number of subjects analysed
    403
    402
    Units: Episodes
    51
    18
    No statistical analyses for this end point

    Secondary: Change in pulse (bpm) - semaglutide 2.4 mg versus placebo

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    End point title
    		 Change in pulse (bpm) - semaglutide 2.4 mg versus placebo [11]
    End point description
    Change in pulse from baseline (week 0) to week 68 is presented. Results are based on the data from on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 2 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses. This endpoint was evaluated based on the SAS which included all randomised subjects exposed to at least one dose of randomised treatment. Number of subjects analysed = number of subjects with available data.
    End point type
    Secondary
    End point timeframe
    From baseline (week 0) to week 68
    Notes
    [11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint compared 'Semaglutide 2.4 mg arm' with 'Placebo arm', thus values only for these two arms are provided.
    End point values
    		 Semaglutide 2.4 mg Placebo
    Number of subjects analysed
    351
    340
    Units: Beats/minute
        arithmetic mean (standard deviation)
    2 ± 9
    0 ± 9
    No statistical analyses for this end point

    Secondary: Change in amylase (U/L) - semaglutide 2.4 mg versus placebo

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    End point title
    		 Change in amylase (U/L) - semaglutide 2.4 mg versus placebo [12]
    End point description
    Change in amylase (units/litre) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 2 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses. This endpoint was evaluated based on the SAS which included all randomised subjects exposed to at least one dose of randomised treatment. Number of subjects analysed = number of subjects with available data.
    End point type
    Secondary
    End point timeframe
    From baseline (week 0) to week 68
    Notes
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint compared 'Semaglutide 2.4 mg arm' with 'Placebo arm', thus values only for these two arms are provided.
    End point values
    		 Semaglutide 2.4 mg Placebo
    Number of subjects analysed
    350
    338
    Units: Ratio of amylase
        geometric mean (geometric coefficient of variation)
    1.24 ± 28.3
    1.06 ± 25.0
    No statistical analyses for this end point

    Secondary: Change in lipase (U/L) - semaglutide 2.4 mg versus placebo

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    End point title
    		 Change in lipase (U/L) - semaglutide 2.4 mg versus placebo [13]
    End point description
    Change in lipase (units/litre) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 2 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses. This endpoint was evaluated based on the SAS which included all randomised subjects exposed to at least one dose of randomised treatment. Number of subjects analysed = number of subjects with available data.
    End point type
    Secondary
    End point timeframe
    From baseline (week 0) to week 68
    Notes
    [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint compared 'Semaglutide 2.4 mg arm' with 'Placebo arm', thus values only for these two arms are provided.
    End point values
    		 Semaglutide 2.4 mg Placebo
    Number of subjects analysed
    350
    338
    Units: Ratio of lipase
        geometric mean (geometric coefficient of variation)
    1.41 ± 57.2
    0.99 ± 51.8
    No statistical analyses for this end point

    Secondary: Change in calcitonin - semaglutide 2.4 mg versus placebo

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    End point title
    		 Change in calcitonin - semaglutide 2.4 mg versus placebo [14]
    End point description
    Change in calcitonin (nanogram/litre) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 2 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses. This endpoint was evaluated based on the SAS which included all randomised subjects exposed to at least one dose of randomised treatment. Number of subjects analysed = number of subjects with available data.
    End point type
    Secondary
    End point timeframe
    From baseline (week 0) to week 68
    Notes
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint compared 'Semaglutide 2.4 mg arm' with 'Placebo arm', thus values only for these two arms are provided.
    End point values
    		 Semaglutide 2.4 mg Placebo
    Number of subjects analysed
    348
    339
    Units: Ratio of calcitonin
        geometric mean (geometric coefficient of variation)
    0.94 ± 60.3
    0.96 ± 38.6
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Week 0 to week 75. Results are based on the SAS which included all randomised subjects exposed to at least one dose of randomised treatment.
    Adverse event reporting additional description
    All presented AEs are treatment-emergent (i.e., TEAEs).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22
    Reporting groups
    Reporting group title
    Semaglutide 1.0 mg
    Reporting group description
    		 Subjects received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Subjects also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Subjects received the treatments as an adjunct to a reduced calorie diet and increased physical activity.

    Reporting group title
    Semaglutide 2.4 mg
    Reporting group description
    		 Subjects received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Subjects also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Subjects received the treatments as an adjunct to a reduced calorie diet and increased physical activity.

    Reporting group title
    Placebo
    Reporting group description
    		 Subjects received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Subjects received the treatments as an adjunct to a reduced calorie diet and increased physical activity.

    Serious adverse events
    		 Semaglutide 1.0 mg Semaglutide 2.4 mg Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    31 / 402 (7.71%)
    40 / 403 (9.93%)
    37 / 402 (9.20%)
         number of deaths (all causes)
    0
    1
    1
         number of deaths resulting from adverse events
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma gastric
         subjects affected / exposed
    1 / 402 (0.25%)
    0 / 403 (0.00%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Adenocarcinoma of colon
         subjects affected / exposed
    1 / 402 (0.25%)
    0 / 403 (0.00%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric cancer
         subjects affected / exposed
    0 / 402 (0.00%)
    0 / 403 (0.00%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric cancer stage IV
         subjects affected / exposed
    0 / 402 (0.00%)
    0 / 403 (0.00%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal lymphoma
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal stromal tumour
         subjects affected / exposed
    1 / 402 (0.25%)
    0 / 403 (0.00%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatocellular carcinoma
         subjects affected / exposed
    0 / 402 (0.00%)
    0 / 403 (0.00%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Invasive ductal breast carcinoma
         subjects affected / exposed
    1 / 402 (0.25%)
    0 / 403 (0.00%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Keratinising squamous cell carcinoma of nasopharynx
         subjects affected / exposed
    0 / 402 (0.00%)
    0 / 403 (0.00%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myeloid leukaemia
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neuroendocrine tumour
         subjects affected / exposed
    1 / 402 (0.25%)
    0 / 403 (0.00%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    0 / 402 (0.00%)
    0 / 403 (0.00%)
    2 / 402 (0.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Uterine cancer
         subjects affected / exposed
    1 / 402 (0.25%)
    0 / 403 (0.00%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Aortic rupture
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    0 / 402 (0.00%)
    2 / 403 (0.50%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypertensive urgency
         subjects affected / exposed
    0 / 402 (0.00%)
    0 / 403 (0.00%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Shock
         subjects affected / exposed
    1 / 402 (0.25%)
    0 / 403 (0.00%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Cardiac pacemaker replacement
         subjects affected / exposed
    1 / 402 (0.25%)
    0 / 403 (0.00%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sperm aspiration
         subjects affected / exposed
    0 / 402 (0.00%)
    0 / 403 (0.00%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Stent placement
         subjects affected / exposed
    0 / 402 (0.00%)
    0 / 403 (0.00%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thyroidectomy
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous
         subjects affected / exposed
    0 / 402 (0.00%)
    0 / 403 (0.00%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    0 / 402 (0.00%)
    0 / 403 (0.00%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Immunisation reaction
         subjects affected / exposed
    1 / 402 (0.25%)
    0 / 403 (0.00%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Uterine polyp
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure
         subjects affected / exposed
    1 / 402 (0.25%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Asthma
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Anaemia postoperative
         subjects affected / exposed
    0 / 402 (0.00%)
    0 / 403 (0.00%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    1 / 402 (0.25%)
    0 / 403 (0.00%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cervical vertebral fracture
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    1 / 402 (0.25%)
    0 / 403 (0.00%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Joint dislocation
         subjects affected / exposed
    0 / 402 (0.00%)
    0 / 403 (0.00%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ligament rupture
         subjects affected / exposed
    1 / 402 (0.25%)
    0 / 403 (0.00%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lisfranc fracture
         subjects affected / exposed
    0 / 402 (0.00%)
    0 / 403 (0.00%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    0 / 402 (0.00%)
    2 / 403 (0.50%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin laceration
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    0 / 402 (0.00%)
    0 / 403 (0.00%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thoracic vertebral fracture
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Traumatic haemothorax
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    2 / 402 (0.50%)
    1 / 403 (0.25%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    1 / 402 (0.25%)
    0 / 403 (0.00%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    2 / 402 (0.50%)
    2 / 403 (0.50%)
    2 / 402 (0.50%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    1 / 402 (0.25%)
    0 / 403 (0.00%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure acute
         subjects affected / exposed
    0 / 402 (0.00%)
    0 / 403 (0.00%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    1 / 402 (0.25%)
    1 / 403 (0.25%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 402 (0.25%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    1 / 402 (0.25%)
    0 / 403 (0.00%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebral artery thrombosis
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatic encephalopathy
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperaesthesia
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemic encephalopathy
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    1 / 402 (0.25%)
    0 / 403 (0.00%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Presyncope
         subjects affected / exposed
    0 / 402 (0.00%)
    0 / 403 (0.00%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal epidural haematoma
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Subarachnoid haemorrhage
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    1 / 402 (0.25%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Cataract
         subjects affected / exposed
    0 / 402 (0.00%)
    0 / 403 (0.00%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Glaucoma
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    3 / 402 (0.75%)
    0 / 403 (0.00%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 402 (0.25%)
    0 / 403 (0.00%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diverticular perforation
         subjects affected / exposed
    0 / 402 (0.00%)
    0 / 403 (0.00%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Food poisoning
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric ulcer
         subjects affected / exposed
    1 / 402 (0.25%)
    0 / 403 (0.00%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    0 / 402 (0.00%)
    0 / 403 (0.00%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    2 / 402 (0.50%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Obstructive pancreatitis
         subjects affected / exposed
    0 / 402 (0.00%)
    0 / 403 (0.00%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 402 (0.00%)
    2 / 403 (0.50%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis acute
         subjects affected / exposed
    0 / 402 (0.00%)
    0 / 403 (0.00%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis chronic
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    1 / 402 (0.25%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Non-alcoholic steatohepatitis
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    2 / 402 (0.50%)
    2 / 403 (0.50%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bladder outlet obstruction
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Stag horn calculus
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ureterolithiasis
         subjects affected / exposed
    0 / 402 (0.00%)
    0 / 403 (0.00%)
    2 / 402 (0.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Neuropathic arthropathy
         subjects affected / exposed
    0 / 402 (0.00%)
    0 / 403 (0.00%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    0 / 402 (0.00%)
    0 / 403 (0.00%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rotator cuff syndrome
         subjects affected / exposed
    1 / 402 (0.25%)
    0 / 403 (0.00%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spondylolisthesis
         subjects affected / exposed
    1 / 402 (0.25%)
    0 / 403 (0.00%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Trigger finger
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    0 / 402 (0.00%)
    0 / 403 (0.00%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    2 / 402 (0.50%)
    0 / 403 (0.00%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colonic abscess
         subjects affected / exposed
    0 / 402 (0.00%)
    0 / 403 (0.00%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cystitis
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    1 / 402 (0.25%)
    0 / 403 (0.00%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Empyema
         subjects affected / exposed
    0 / 402 (0.00%)
    0 / 403 (0.00%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    3 / 402 (0.75%)
    3 / 403 (0.74%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    1 / 3
    2 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Joint abscess
         subjects affected / exposed
    0 / 402 (0.00%)
    0 / 403 (0.00%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Kidney infection
         subjects affected / exposed
    0 / 402 (0.00%)
    0 / 403 (0.00%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    0 / 402 (0.00%)
    0 / 403 (0.00%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pharyngitis streptococcal
         subjects affected / exposed
    0 / 402 (0.00%)
    0 / 403 (0.00%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 402 (0.25%)
    1 / 403 (0.25%)
    2 / 402 (0.50%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia influenzal
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    1 / 402 (0.25%)
    0 / 403 (0.00%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    3 / 402 (0.75%)
    0 / 403 (0.00%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Wound infection staphylococcal
         subjects affected / exposed
    0 / 402 (0.00%)
    0 / 403 (0.00%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Cachexia
         subjects affected / exposed
    1 / 402 (0.25%)
    0 / 403 (0.00%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Decreased appetite
         subjects affected / exposed
    1 / 402 (0.25%)
    0 / 403 (0.00%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    2 / 402 (0.50%)
    1 / 403 (0.25%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetes mellitus inadequate control
         subjects affected / exposed
    0 / 402 (0.00%)
    0 / 403 (0.00%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetic ketoacidosis
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diabetic metabolic decompensation
         subjects affected / exposed
    0 / 402 (0.00%)
    0 / 403 (0.00%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    1 / 402 (0.25%)
    0 / 403 (0.00%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ketoacidosis
         subjects affected / exposed
    0 / 402 (0.00%)
    1 / 403 (0.25%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lactic acidosis
         subjects affected / exposed
    1 / 402 (0.25%)
    0 / 403 (0.00%)
    0 / 402 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Obesity
         subjects affected / exposed
    0 / 402 (0.00%)
    0 / 403 (0.00%)
    1 / 402 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Semaglutide 1.0 mg Semaglutide 2.4 mg Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    261 / 402 (64.93%)
    284 / 403 (70.47%)
    190 / 402 (47.26%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    33 / 402 (8.21%)
    31 / 403 (7.69%)
    20 / 402 (4.98%)
         occurrences all number
    48
    40
    27
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    19 / 402 (4.73%)
    28 / 403 (6.95%)
    4 / 402 (1.00%)
         occurrences all number
    26
    29
    4
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    9 / 402 (2.24%)
    24 / 403 (5.96%)
    11 / 402 (2.74%)
         occurrences all number
    12
    30
    13
    Constipation
         subjects affected / exposed
    51 / 402 (12.69%)
    70 / 403 (17.37%)
    22 / 402 (5.47%)
         occurrences all number
    70
    82
    26
    Diarrhoea
         subjects affected / exposed
    88 / 402 (21.89%)
    86 / 403 (21.34%)
    48 / 402 (11.94%)
         occurrences all number
    157
    141
    66
    Dyspepsia
         subjects affected / exposed
    27 / 402 (6.72%)
    25 / 403 (6.20%)
    5 / 402 (1.24%)
         occurrences all number
    27
    30
    5
    Flatulence
         subjects affected / exposed
    21 / 402 (5.22%)
    16 / 403 (3.97%)
    7 / 402 (1.74%)
         occurrences all number
    25
    21
    9
    Nausea
         subjects affected / exposed
    128 / 402 (31.84%)
    135 / 403 (33.50%)
    37 / 402 (9.20%)
         occurrences all number
    196
    248
    45
    Vomiting
         subjects affected / exposed
    54 / 402 (13.43%)
    86 / 403 (21.34%)
    11 / 402 (2.74%)
         occurrences all number
    93
    186
    12
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    24 / 402 (5.97%)
    23 / 403 (5.71%)
    20 / 402 (4.98%)
         occurrences all number
    27
    29
    20
    Back pain
         subjects affected / exposed
    28 / 402 (6.97%)
    27 / 403 (6.70%)
    14 / 402 (3.48%)
         occurrences all number
    30
    30
    15
    Infections and infestations
    Gastroenteritis
         subjects affected / exposed
    21 / 402 (5.22%)
    11 / 403 (2.73%)
    12 / 402 (2.99%)
         occurrences all number
    25
    12
    14
    Nasopharyngitis
         subjects affected / exposed
    47 / 402 (11.69%)
    68 / 403 (16.87%)
    59 / 402 (14.68%)
         occurrences all number
    69
    115
    92
    Upper respiratory tract infection
         subjects affected / exposed
    37 / 402 (9.20%)
    42 / 403 (10.42%)
    38 / 402 (9.45%)
         occurrences all number
    54
    48
    50
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    29 / 402 (7.21%)
    38 / 403 (9.43%)
    15 / 402 (3.73%)
         occurrences all number
    33
    41
    17

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    27 Jul 2018
    Inclusion of genetic biosamples for future analysis for applicable countries. Removal of discontinuation criteria for trial products for subjects enrolled in violation with exclusion/inclusion criteria. Removal of classification of risks, inclusion of a reference to the investigator’s brochure. Removal of persistent criteria from exploratory endpoint regarding micro/macro albuminuria.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/33667417
    http://www.ncbi.nlm.nih.gov/pubmed/32441473
    http://www.ncbi.nlm.nih.gov/pubmed/30122305
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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