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    Clinical Trial Results:
    Efficacy and Safety of Oral Semaglutide versus Placebo in Subjects with Type 2 Diabetes Mellitus treated with insulin - A 52-week, randomised, placebo-controlled trial, double-blinded during the initial 26 weeks.

    Summary
    EudraCT number
    2016-000988-16
    Trial protocol
    FR   GR   PL  
    Global end of trial date
    22 Aug 2018

    Results information
    Results version number
    v1(current)
    This version publication date
    05 Sep 2019
    First version publication date
    05 Sep 2019
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    NN9924-4280
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT03021187
    WHO universal trial number (UTN)
    U1111-1180-3637
    Sponsors
    Sponsor organisation name
    Novo Nordisk A/S
    Sponsor organisation address
    Novo Allé, Bagsvaerd, Denmark, 2880
    Public contact
    Clinical Reporting Anchor and Disclosure (1452), Novo Nordisk A/S, clinicaltrials@novonordisk.com
    Scientific contact
    Clinical Reporting 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
    12 Feb 2019
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    18 Jan 2018
    Global end of trial reached?
    Yes
    Global end of trial date
    22 Aug 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To compare the effect of once-daily dosing of three dose levels of oral semaglutide (3 mg, 7 mg and 14 mg) versus placebo on glycaemic control in subjects with type 2 diabetes mellitus treated with insulin.
    Protection of trial subjects
    The trial was conducted in accordance with the Declaration of Helsinki (2013), ICH Good Clinical Practice, including archiving of essential documents (1996), and 21 CFR 312.120.
    Background therapy
    The subjects continued to receive their regular dose of insulin throughout the trial. The 52-week randomised treatment period was split into two treatment periods; an initial 26-week fixed insulin treatment period where the insulin treatment was restricted, followed by a 26-week period where the insulin treatment was adjustable without any restrictions.
    Evidence for comparator
    Not applicable
    Actual start date of recruitment
    02 Feb 2017
    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
    Canada: 41
    Country: Number of subjects enrolled
    France: 38
    Country: Number of subjects enrolled
    Greece: 31
    Country: Number of subjects enrolled
    India: 51
    Country: Number of subjects enrolled
    Japan: 194
    Country: Number of subjects enrolled
    Mexico: 40
    Country: Number of subjects enrolled
    Poland: 65
    Country: Number of subjects enrolled
    Russian Federation: 61
    Country: Number of subjects enrolled
    United States: 210
    Worldwide total number of subjects
    731
    EEA total number of subjects
    134
    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)
    453
    From 65 to 84 years
    276
    85 years and over
    2

    Subject disposition

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    Recruitment
    Recruitment details
    The trial was conducted at 111 sites in 9 countries: Canada (7), France (10), Greece (6), India (9), Japan (18), Mexico (2), Poland (4), Russian Federation (5) and United States (48). Following sites were approved by the IRB/IEC but didn't randomise subjects: France (2), India (1), Japan (1) and United States (3).

    Pre-assignment
    Screening details
    Not applicable

    Period 1
    Period 1 title
    Overall Period
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Investigator, Subject

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Oral semaglutide 3 mg
    Arm description
    Subjects were randomised to receive once-daily semaglutide 3 mg tablets for a period of 52 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    Semaglutide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects were to take the 3 mg semaglutide tablets once daily in the morning in a fasting state and at least 30 minutes before the first meal of the day for 52 weeks. The tablet was to be taken with about 120 ml (half a glass) of water. Subjects had to swallow the tablet as a whole and not break or chew it. Oral medication other than trial product could be taken 30 minutes after administration of trial product.

    Arm title
    Oral semaglutide 7 mg
    Arm description
    Subjects were randomised to receive once-daily semaglutide tablet in a dose escalation manner for 52 weeks: 3 mg from weeks 1-4 and 7 mg from weeks 5-52.
    Arm type
    Experimental

    Investigational medicinal product name
    Semaglutide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects were to take 3 mg semaglutide tablets once daily in the morning in a fasting state for first 4 weeks. They were to take 7 mg semaglutide tablets for the rest of the treatment period upto 52 weeks. The tablet was to be taken at least 30 minutes before the first meal of the day with about 120 ml (half a glass) of water. Subjects had to swallow the tablet as a whole and not break or chew it. Oral medication other than trial product could be taken 30 minutes after administration of trial product.

    Arm title
    Oral semaglutide 14 mg
    Arm description
    Subjects were randomised to receive once-daily semaglutide tablets in a dose escalation manner for 52 weeks: 3 mg from weeks 1-4, 7 mg from weeks 5-8 and 14 mg from weeks 9-52.
    Arm type
    Experimental

    Investigational medicinal product name
    Semaglutide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects were to take 3 mg semaglutide for first 4 weeks followed by 7 mg tablets for another 4 weeks and then 14 mg tablets for the rest of the treatment period upto 52 weeks in the fasting state. The tablet was to be taken at least 30 minutes before the first meal of the day with about 120 ml (half a glass) of water. Subjects had to swallow the tablet as a whole and not break or chew it. Oral medication other than trial product could be taken 30 minutes after administration of trial product.

    Arm title
    Placebo
    Arm description
    Subjects were randomised to receive once-daily placebo tablets for a period of 52 weeks.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects in the placebo group were to take placebo tablets once daily in the morning in a fasting state for 52 weeks. The tablet was to be taken with about 120 ml (half a glass) of water. Subjects had to swallow the tablet as a whole and not break or chew it. Oral medication other than trial product could be taken 30 minutes after administration of trial product.

    Number of subjects in period 1
    Oral semaglutide 3 mg Oral semaglutide 7 mg Oral semaglutide 14 mg Placebo
    Started
    184
    182
    181
    184
    Exposed
    184
    181
    181
    184
    Completed
    174
    173
    175
    175
    Not completed
    10
    9
    6
    9
         Adverse event, serious fatal
    -
    -
    3
    -
         Consent withdrawn by subject
    -
    6
    2
    5
         Lost to follow-up
    10
    3
    1
    4

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Oral semaglutide 3 mg
    Reporting group description
    Subjects were randomised to receive once-daily semaglutide 3 mg tablets for a period of 52 weeks.

    Reporting group title
    Oral semaglutide 7 mg
    Reporting group description
    Subjects were randomised to receive once-daily semaglutide tablet in a dose escalation manner for 52 weeks: 3 mg from weeks 1-4 and 7 mg from weeks 5-52.

    Reporting group title
    Oral semaglutide 14 mg
    Reporting group description
    Subjects were randomised to receive once-daily semaglutide tablets in a dose escalation manner for 52 weeks: 3 mg from weeks 1-4, 7 mg from weeks 5-8 and 14 mg from weeks 9-52.

    Reporting group title
    Placebo
    Reporting group description
    Subjects were randomised to receive once-daily placebo tablets for a period of 52 weeks.

    Reporting group values
    Oral semaglutide 3 mg Oral semaglutide 7 mg Oral semaglutide 14 mg Placebo Total
    Number of subjects
    184 182 181 184 731
    Age Categorical
    Units: Subjects
        Adults (18 to 65 years)
    110 121 108 114 453
        From 65 to 75 years
    67 49 60 63 239
        From 75 to 85 years
    7 12 11 7 37
        85 years and above
    0 0 2 0 2
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    61 ± 9 60 ± 10 61 ± 10 60 ± 10 -
    Gender Categorical
    Units: Subjects
        Female
    82 79 96 79 336
        Male
    102 103 85 105 395
    HbA1c
    Glycosylated haemoglobin
    Units: %-points
        arithmetic mean (standard deviation)
    8.2 ± 0.7 8.2 ± 0.7 8.2 ± 0.7 8.2 ± 0.7 -

    End points

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    End points reporting groups
    Reporting group title
    Oral semaglutide 3 mg
    Reporting group description
    Subjects were randomised to receive once-daily semaglutide 3 mg tablets for a period of 52 weeks.

    Reporting group title
    Oral semaglutide 7 mg
    Reporting group description
    Subjects were randomised to receive once-daily semaglutide tablet in a dose escalation manner for 52 weeks: 3 mg from weeks 1-4 and 7 mg from weeks 5-52.

    Reporting group title
    Oral semaglutide 14 mg
    Reporting group description
    Subjects were randomised to receive once-daily semaglutide tablets in a dose escalation manner for 52 weeks: 3 mg from weeks 1-4, 7 mg from weeks 5-8 and 14 mg from weeks 9-52.

    Reporting group title
    Placebo
    Reporting group description
    Subjects were randomised to receive once-daily placebo tablets for a period of 52 weeks.

    Primary: Change in HbA1c (in-trial observation period: week 26)

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    End point title
    Change in HbA1c (in-trial observation period: week 26)
    End point description
    Mean change from baseline (week 0) to week 26 in glycosylated haemoglobin (HbA1c). The endpoint was evaluated based on data from the in-trial observation period. In-trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. Analysis population: Full analysis set which comprised all randomised subjects. "Number of subjects analysed" = subjects with available data.
    End point type
    Primary
    End point timeframe
    From baseline to week 26
    End point values
    Oral semaglutide 3 mg Oral semaglutide 7 mg Oral semaglutide 14 mg Placebo
    Number of subjects analysed
    176
    174
    173
    176
    Units: Percentage of HbA1c
        arithmetic mean (standard deviation)
    -0.5 ± 1.0
    -1.0 ± 1.1
    -1.3 ± 1.1
    -0.1 ± 0.9
    Statistical analysis title
    Semaglutide 3 mg vs Placebo
    Statistical analysis description
    Missing post-baseline values were imputed by a pattern mixture model using multiple imputation. Imputation was from own treatment arm and same treatment status. Change from baseline was analysed using an analysis of covariance (ANCOVA) model with treatment, strata, interaction strata, and region as categorical fixed effects and baseline value as covariate for each of the 1000 imputed complete datasets, and pooled by Rubin's rule to draw inference.
    Comparison groups
    Oral semaglutide 3 mg v Placebo
    Number of subjects included in analysis
    352
    Analysis specification
    Pre-specified
    Analysis type
    superiority [1]
    P-value
    < 0.0001 [2]
    Method
    ANCOVA
    Parameter type
    Treatment difference
    Point estimate
    -0.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.7
         upper limit
    -0.3
    Notes
    [1] - This hypothesis was controlled for multiplicity. The estimated treatment effect includes the effect of any rescue medication and any effect after premature trial product discontinuation (treatment policy estimand). Number of subjects included in analysis = Number of subjects in the FAS, who contributed to the analysis.
    [2] - Unadjusted two-sided p-value for test of no difference from 0.
    Statistical analysis title
    Semaglutide 7 mg vs Placebo
    Statistical analysis description
    Missing post-baseline values were imputed by a pattern mixture model using multiple imputation. Imputation was from own treatment arm and same treatment status. Change from baseline was analysed using an ANCOVA model with treatment, strata, interaction strata and region as categorical fixed effects and baseline value as covariate for each of the 1000 imputed complete datasets, and pooled by Rubin's rule to draw inference.
    Comparison groups
    Oral semaglutide 7 mg v Placebo
    Number of subjects included in analysis
    350
    Analysis specification
    Pre-specified
    Analysis type
    superiority [3]
    P-value
    < 0.0001 [4]
    Method
    ANCOVA
    Parameter type
    Treatment difference
    Point estimate
    -0.9
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.1
         upper limit
    -0.7
    Notes
    [3] - This hypothesis was controlled for multiplicity. The estimated treatment effect includes the effect of any rescue medication and any effect after premature trial product discontinuation (treatment policy estimand). Number of subjects included in analysis = Number of subjects in the FAS, who contributed to the analysis.
    [4] - Unadjusted two-sided p-value for test of no difference from 0.
    Statistical analysis title
    Semaglutide 14 mg vs Placebo
    Statistical analysis description
    Missing post-baseline values were imputed by a pattern mixture model using multiple imputation. Imputation was from own treatment arm and same treatment status. Change from baseline was analysed using an ANCOVA model with treatment, strata, interaction strata and region as categorical fixed effects and baseline value as covariate for each of the 1000 imputed complete datasets, and pooled by Rubin's rule to draw inference.
    Comparison groups
    Oral semaglutide 14 mg v Placebo
    Number of subjects included in analysis
    349
    Analysis specification
    Pre-specified
    Analysis type
    superiority [5]
    P-value
    < 0.0001 [6]
    Method
    ANCOVA
    Parameter type
    Treatment difference
    Point estimate
    -1.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.4
         upper limit
    -1
    Notes
    [5] - This hypothesis was controlled for multiplicity. The estimated treatment effect includes the effect of any rescue medication and any effect after premature trial product discontinuation (treatment policy estimand). Number of subjects included in analysis = Number of subjects in the FAS, who contributed to the analysis.
    [6] - Unadjusted two-sided p-value for test of no difference from 0.

    Primary: Change in HbA1c (on-treatment without rescue medication observation period: week 26)

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    End point title
    Change in HbA1c (on-treatment without rescue medication observation period: week 26)
    End point description
    Mean change from baseline (week 0) to week 26 in HbA1c. The endpoint was analysed based on data from the on-treatment without rescue medication observation period. On-treatment without rescue medication observation period started at the date of the first dose of trial product and includes the period after initiation of rescue medication, if any, and excludes the period after premature trial discontinuation, if any. Analysis population: Full analysis set which comprised all randomised subjects. "Number of subjects analysed" = subjects with available data.
    End point type
    Primary
    End point timeframe
    From baseline to week 26
    End point values
    Oral semaglutide 3 mg Oral semaglutide 7 mg Oral semaglutide 14 mg Placebo
    Number of subjects analysed
    162
    157
    146
    161
    Units: Percentage of HbA1c
        arithmetic mean (standard deviation)
    -0.6 ± 1.1
    -1.1 ± 1.0
    -1.4 ± 0.9
    -0.1 ± 0.8
    Statistical analysis title
    Semaglutide 3 mg vs Placebo
    Statistical analysis description
    Changes from baseline were analysed using a mixed model for repeated measurements model with treatment, strata, interaction strata, and region as categorical fixed effects and baseline value as covariate, all nested within visit, and an unstructured residual covariance matrix.
    Comparison groups
    Oral semaglutide 3 mg v Placebo
    Number of subjects included in analysis
    323
    Analysis specification
    Pre-specified
    Analysis type
    superiority [7]
    P-value
    < 0.0001 [8]
    Method
    Mixed model for repeated measurements
    Parameter type
    Treatment difference
    Point estimate
    -0.6
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.7
         upper limit
    -0.4
    Notes
    [7] - Analysis was based on hypothetical estimand. This hypothesis was not controlled for multiplicity. "Subjects in this analysis"=number of subjects with available data; all subjects in the FAS with data contributed to the analysis.
    [8] - Unadjusted two-sided p-value for test of no difference from 0.
    Statistical analysis title
    Semaglutide 7 mg vs Placebo
    Statistical analysis description
    Changes from baseline were analysed using a mixed model for repeated measurements model with treatment, strata, interaction strata, and region as categorical fixed effects and baseline value as covariate, all nested within visit, and an unstructured residual covariance matrix.
    Comparison groups
    Oral semaglutide 7 mg v Placebo
    Number of subjects included in analysis
    318
    Analysis specification
    Pre-specified
    Analysis type
    superiority [9]
    P-value
    < 0.0001 [10]
    Method
    Mixed model for repeated measurements
    Parameter type
    Treatment difference
    Point estimate
    -1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.2
         upper limit
    -0.8
    Notes
    [9] - Analysis was based on hypothetical estimand. This hypothesis was not controlled for multiplicity. "Subjects in this analysis"=number of subjects with available data; all subjects in the FAS with data contributed to the analysis.
    [10] - Unadjusted two-sided p-value for test of no difference from 0.
    Statistical analysis title
    Semaglutide 14 mg vs Placebo
    Statistical analysis description
    Changes from baseline were analysed using a mixed model for repeated measurements model with treatment, strata, interaction strata, and region as categorical fixed effects and baseline value as covariate, all nested within visit, and an unstructured residual covariance matrix.
    Comparison groups
    Oral semaglutide 14 mg v Placebo
    Number of subjects included in analysis
    307
    Analysis specification
    Pre-specified
    Analysis type
    superiority [11]
    P-value
    < 0.0001 [12]
    Method
    Mixed model for repeated measurements
    Parameter type
    Treatment difference
    Point estimate
    -1.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.6
         upper limit
    -1.2
    Notes
    [11] - Analysis was based on hypothetical estimand. This hypothesis was not controlled for multiplicity. "Subjects in this analysis"=number of subjects with available data; all subjects in the FAS with data contributed to the analysis.
    [12] - Unadjusted two-sided p-value for test of no difference from 0.

    Secondary: Change in body weight (kg) (in-trial observation period: week 26)

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    End point title
    Change in body weight (kg) (in-trial observation period: week 26)
    End point description
    Change from baseline (week 0) in body weight to week 26. The endpoint was evaluated based on data from the in-trial observation period. In-trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. Analysis population: Full analysis set which comprised all randomised subjects. "Number of subjects analysed" = subjects with available data.
    End point type
    Secondary
    End point timeframe
    From baseline to 26 weeks
    End point values
    Oral semaglutide 3 mg Oral semaglutide 7 mg Oral semaglutide 14 mg Placebo
    Number of subjects analysed
    177
    174
    173
    177
    Units: kilograms (kg)
        arithmetic mean (standard deviation)
    -1.4 ± 3.1
    -2.6 ± 5.2
    -3.7 ± 4.0
    -0.5 ± 2.5
    No statistical analyses for this end point

    Secondary: Change in body weight (kg) (on-treatment period without rescue medication observation period: week 26)

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    End point title
    Change in body weight (kg) (on-treatment period without rescue medication observation period: week 26)
    End point description
    Mean change from baseline to week 26 in body weight. The endpoint was evaluated based on data from the on-treatment without rescue medication observation period. On-treatment without rescue medication observation period started at the date of the first dose of trial product and included the period after initiation of rescue medication, if any, and excluded the period after premature trial discontinuation, if any. Analysis population: Full analysis set which comprised all randomised subjects. "Number of subjects analysed" = subjects with available data.
    End point type
    Secondary
    End point timeframe
    From baseline to week 26
    End point values
    Oral semaglutide 3 mg Oral semaglutide 7 mg Oral semaglutide 14 mg Placebo
    Number of subjects analysed
    163
    157
    146
    162
    Units: kg
        arithmetic mean (standard deviation)
    -1.5 ± 3.1
    -3.0 ± 3.7
    -3.9 ± 3.6
    -0.5 ± 2.4
    No statistical analyses for this end point

    Secondary: Change in HbA1c (week 52)

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    End point title
    Change in HbA1c (week 52)
    End point description
    Change from baseline (week 0) in HbA1c to week 52. The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. Analysis population: Full analysis set which comprised all randomised subjects. "Number of subjects analysed" = subjects with available data.
    End point type
    Secondary
    End point timeframe
    From baseline to week 52
    End point values
    Oral semaglutide 3 mg Oral semaglutide 7 mg Oral semaglutide 14 mg Placebo
    Number of subjects analysed
    173
    169
    168
    172
    Units: Percentage of HbA1c
        arithmetic mean (standard deviation)
    -0.6 ± 1.0
    -0.9 ± 1.1
    -1.2 ± 1.0
    -0.2 ± 0.8
    No statistical analyses for this end point

    Secondary: Change in body weight (kg) (week 52)

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    End point title
    Change in body weight (kg) (week 52)
    End point description
    Change from baseline (week 0) in body weight to week 52. The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. Analysis population: Full analysis set which comprised all randomised subjects. "Number of subjects analysed" = subjects with available data.
    End point type
    Secondary
    End point timeframe
    From baseline to week 52
    End point values
    Oral semaglutide 3 mg Oral semaglutide 7 mg Oral semaglutide 14 mg Placebo
    Number of subjects analysed
    174
    171
    170
    173
    Units: kg
        arithmetic mean (standard deviation)
    -0.9 ± 3.9
    -2.2 ± 5.2
    -3.8 ± 5.8
    0.5 ± 3.2
    No statistical analyses for this end point

    Secondary: Change in fasting plasma glucose (FPG) (week 26)

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    End point title
    Change in fasting plasma glucose (FPG) (week 26)
    End point description
    Change from baseline (week 0) in fasting plasma glucose to week 26. The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. Analysis population: Full analysis set which comprised all randomised subjects. "Number of subjects analysed" = subjects with available data.
    End point type
    Secondary
    End point timeframe
    From baseline to week 26
    End point values
    Oral semaglutide 3 mg Oral semaglutide 7 mg Oral semaglutide 14 mg Placebo
    Number of subjects analysed
    175
    173
    173
    175
    Units: mmol/L
        arithmetic mean (standard deviation)
    -0.45 ± 3.35
    -1.14 ± 3.08
    -1.36 ± 2.72
    0.51 ± 2.84
    No statistical analyses for this end point

    Secondary: Change in fasting plasma glucose (FPG) (week 52)

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    End point title
    Change in fasting plasma glucose (FPG) (week 52)
    End point description
    Change from baseline (week 0) in fasting plasma glucose to week 52. The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. Analysis population: Full analysis set which comprised all randomised subjects. "Number of subjects analysed" = subjects with available data.
    End point type
    Secondary
    End point timeframe
    From baseline to week 52
    End point values
    Oral semaglutide 3 mg Oral semaglutide 7 mg Oral semaglutide 14 mg Placebo
    Number of subjects analysed
    172
    168
    169
    172
    Units: mmol/L
        arithmetic mean (standard deviation)
    -0.81 ± 3.21
    -1.12 ± 2.91
    -1.60 ± 2.65
    -0.09 ± 2.97
    No statistical analyses for this end point

    Secondary: If a subject achieves (yes/no): HbA1c < 7.0% (53 mmol/mol) (American Diabetes Association (ADA) target) (week 26)

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    End point title
    If a subject achieves (yes/no): HbA1c < 7.0% (53 mmol/mol) (American Diabetes Association (ADA) target) (week 26)
    End point description
    Number of subjects achieving HbA1c < 7.0 % (53 mmol/mol) according to American Diabetes Association (ADA) target, at week 26. The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. Analysis population: Full analysis set which comprised all randomised subjects. "Number of subjects analysed" = subjects with available data.
    End point type
    Secondary
    End point timeframe
    After week 26
    End point values
    Oral semaglutide 3 mg Oral semaglutide 7 mg Oral semaglutide 14 mg Placebo
    Number of subjects analysed
    176
    174
    173
    176
    Units: Subjects
        Yes
    50
    74
    101
    12
        No
    126
    100
    72
    164
    No statistical analyses for this end point

    Secondary: If a subject achieves (yes/no): HbA1c < 7.0% (53 mmol/mol) (American Diabetes Association (ADA) target) (week 52)

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    End point title
    If a subject achieves (yes/no): HbA1c < 7.0% (53 mmol/mol) (American Diabetes Association (ADA) target) (week 52)
    End point description
    Number of subjects achieving HbA1c < 7.0 % (53 mmol/mol) according to the ADA target, at week 52. The endpoint was evaluated based on data from the in-trial observation period. In trial observation period started at the date of randomisation and included the period after initiation of rescue medication and/or premature trial product discontinuation, if any. Analysis population: Full analysis set which comprised all randomised subjects. "Number of subjects analysed" = subjects with available data.
    End point type
    Secondary
    End point timeframe
    After week 52
    End point values
    Oral semaglutide 3 mg Oral semaglutide 7 mg Oral semaglutide 14 mg Placebo
    Number of subjects analysed
    173
    169
    168
    172
    Units: Subjects
        Yes
    50
    67
    91
    16
        No
    123
    102
    77
    156
    No statistical analyses for this end point

    Secondary: Number of treatment-emergent adverse events (TEAEs) during exposure to trial product

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    End point title
    Number of treatment-emergent adverse events (TEAEs) during exposure to trial product
    End point description
    A treatment-emergent adverse event (TEAE) is defined as an adverse event with onset in the on-treatment observation period. This period started at the date of first dose of trial product and included the period after initiation of rescue medication, if any, and excluded the period after premature trial product discontinuation, if any. The safety analysis set (SAS) comprised all randomised subjects who received at least one dose of trial product. Subjects contribute to a treatment group based on the trial product they actually received for the majority of the on-treatment observation period. "Number of subjects analysed" = subjects with available data.
    End point type
    Secondary
    End point timeframe
    Assessed up to approximately 57 weeks
    End point values
    Oral semaglutide 3 mg Oral semaglutide 7 mg Oral semaglutide 14 mg Placebo
    Number of subjects analysed
    184
    181
    181
    184
    Units: Events
    626
    555
    586
    464
    No statistical analyses for this end point

    Secondary: Number of treatment-emergent severe or blood glucose-confirmed symptomatic hypoglycaemic episodes during exposure to trial product

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    End point title
    Number of treatment-emergent severe or blood glucose-confirmed symptomatic hypoglycaemic episodes during exposure to trial product
    End point description
    Hypoglycaemic episodes defined as treatment-emergent if the onset of the episode occurs within the on-treatment observation period. Severe or BG-confirmed symptomatic hypoglycaemia is an episode that is severe according to the ADA classification or blood glucose-confirmed by a plasma glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. The safety analysis set (SAS) comprised all randomised subjects who received at least one dose of trial product. Subjects contribute to a treatment group based on the trial product they actually received for the majority of the on-treatment observation period. "Number of subjects analysed" = subjects with available data.
    End point type
    Secondary
    End point timeframe
    Assessed up to approximately 57 weeks
    End point values
    Oral semaglutide 3 mg Oral semaglutide 7 mg Oral semaglutide 14 mg Placebo
    Number of subjects analysed
    184
    181
    181
    184
    Units: Episodes
    196
    180
    147
    156
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From the date of first dose of trial product (week 0) to end of treatment (week 52) + 5 weeks of follow-up (until week 57).
    Adverse event reporting additional description
    Results are based on the SAS. All presented AEs are TEAEs which were recorded during the exposure to trial products. AEs with onset during the on-treatment observation period were considered treatment-emergent. Number of deaths causally related to treatment’ is the data considered to present under ‘total number of deaths resulting from AEs.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    20
    Reporting groups
    Reporting group title
    Oral Semaglutide 3 mg
    Reporting group description
    Subjects were to take oral semaglutide 3 mg tablets once daily from week 1 to 52.

    Reporting group title
    Oral Semaglutide 7 mg
    Reporting group description
    Subjects were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 52: 3 mg from week 1 to 4 and 7 mg from week 5 to 52.

    Reporting group title
    Oral Semaglutide 14 mg
    Reporting group description
    Subjects were to take oral semaglutide tablets once daily in a dose escalation manner from week 1 to 52: 3 mg from week 1 to 4, 7 mg from week 5 to 8 and 14 mg from week 9 to 52.

    Reporting group title
    Placebo
    Reporting group description
    Subjects were to take oral semaglutide placebo tablets once daily from week 1 to 52.

    Serious adverse events
    Oral Semaglutide 3 mg Oral Semaglutide 7 mg Oral Semaglutide 14 mg Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    25 / 184 (13.59%)
    19 / 181 (10.50%)
    12 / 181 (6.63%)
    17 / 184 (9.24%)
         number of deaths (all causes)
    0
    0
    3
    0
         number of deaths resulting from adverse events
    0
    0
    1
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma of colon
         subjects affected / exposed
    0 / 184 (0.00%)
    0 / 181 (0.00%)
    1 / 181 (0.55%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast cancer
         subjects affected / exposed
    0 / 184 (0.00%)
    1 / 181 (0.55%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    1 / 184 (0.54%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal adenocarcinoma
         subjects affected / exposed
    1 / 184 (0.54%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vulval cancer
         subjects affected / exposed
    0 / 184 (0.00%)
    1 / 181 (0.55%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Aortic stenosis
         subjects affected / exposed
    0 / 184 (0.00%)
    1 / 181 (0.55%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    0 / 184 (0.00%)
    2 / 181 (1.10%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    0 / 184 (0.00%)
    1 / 181 (0.55%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral artery thrombosis
         subjects affected / exposed
    1 / 184 (0.54%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Hip arthroplasty
         subjects affected / exposed
    0 / 184 (0.00%)
    1 / 181 (0.55%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hysterectomy
         subjects affected / exposed
    0 / 184 (0.00%)
    1 / 181 (0.55%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spinal operation
         subjects affected / exposed
    1 / 184 (0.54%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thyroidectomy
         subjects affected / exposed
    0 / 184 (0.00%)
    0 / 181 (0.00%)
    1 / 181 (0.55%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    1 / 184 (0.54%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    0 / 184 (0.00%)
    0 / 181 (0.00%)
    1 / 181 (0.55%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 184 (0.00%)
    1 / 181 (0.55%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    1 / 184 (0.54%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Systemic inflammatory response syndrome
         subjects affected / exposed
    1 / 184 (0.54%)
    1 / 181 (0.55%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Prostatomegaly
         subjects affected / exposed
    0 / 184 (0.00%)
    0 / 181 (0.00%)
    1 / 181 (0.55%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uterine polyp
         subjects affected / exposed
    0 / 184 (0.00%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    1 / 184 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vaginal prolapse
         subjects affected / exposed
    0 / 184 (0.00%)
    1 / 181 (0.55%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    1 / 184 (0.54%)
    1 / 181 (0.55%)
    1 / 181 (0.55%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 184 (0.54%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    1 / 184 (0.54%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 184 (0.54%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Depression suicidal
         subjects affected / exposed
    0 / 184 (0.00%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    1 / 184 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mental status changes
         subjects affected / exposed
    1 / 184 (0.54%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Spinal myelogram
         subjects affected / exposed
    1 / 184 (0.54%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Clavicle fracture
         subjects affected / exposed
    1 / 184 (0.54%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    1 / 184 (0.54%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    1 / 184 (0.54%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Jaw fracture
         subjects affected / exposed
    1 / 184 (0.54%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint dislocation
         subjects affected / exposed
    1 / 184 (0.54%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postoperative thoracic procedure complication
         subjects affected / exposed
    0 / 184 (0.00%)
    1 / 181 (0.55%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    0 / 184 (0.00%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    1 / 184 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    0 / 184 (0.00%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    1 / 184 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    0 / 184 (0.00%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    1 / 184 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    1 / 184 (0.54%)
    1 / 181 (0.55%)
    1 / 181 (0.55%)
    1 / 184 (0.54%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    1 / 184 (0.54%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    2 / 184 (1.09%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    1 / 184 (0.54%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    0 / 184 (0.00%)
    1 / 181 (0.55%)
    0 / 181 (0.00%)
    1 / 184 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure chronic
         subjects affected / exposed
    1 / 184 (0.54%)
    1 / 181 (0.55%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    0 / 184 (0.00%)
    0 / 181 (0.00%)
    1 / 181 (0.55%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    0 / 184 (0.00%)
    1 / 181 (0.55%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 184 (0.54%)
    0 / 181 (0.00%)
    1 / 181 (0.55%)
    1 / 184 (0.54%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Silent myocardial infarction
         subjects affected / exposed
    0 / 184 (0.00%)
    0 / 181 (0.00%)
    1 / 181 (0.55%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    0 / 184 (0.00%)
    1 / 181 (0.55%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Brain stem infarction
         subjects affected / exposed
    0 / 184 (0.00%)
    1 / 181 (0.55%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Carpal tunnel syndrome
         subjects affected / exposed
    0 / 184 (0.00%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    1 / 184 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    0 / 184 (0.00%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    1 / 184 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoglycaemic unconsciousness
         subjects affected / exposed
    2 / 184 (1.09%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ischaemic cerebral infarction
         subjects affected / exposed
    0 / 184 (0.00%)
    0 / 181 (0.00%)
    1 / 181 (0.55%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    2 / 184 (1.09%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    2 / 184 (1.09%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lacunar infarction
         subjects affected / exposed
    0 / 184 (0.00%)
    1 / 181 (0.55%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mononeuropathy
         subjects affected / exposed
    0 / 184 (0.00%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    1 / 184 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    0 / 184 (0.00%)
    1 / 181 (0.55%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    White matter lesion
         subjects affected / exposed
    0 / 184 (0.00%)
    1 / 181 (0.55%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 184 (0.54%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Normocytic anaemia
         subjects affected / exposed
    1 / 184 (0.54%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Cataract
         subjects affected / exposed
    1 / 184 (0.54%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    1 / 184 (0.54%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Glaucoma
         subjects affected / exposed
    1 / 184 (0.54%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retinal detachment
         subjects affected / exposed
    1 / 184 (0.54%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    0 / 184 (0.00%)
    0 / 181 (0.00%)
    1 / 181 (0.55%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal inflammation
         subjects affected / exposed
    1 / 184 (0.54%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 184 (0.00%)
    0 / 181 (0.00%)
    1 / 181 (0.55%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Impaired gastric emptying
         subjects affected / exposed
    0 / 184 (0.00%)
    0 / 181 (0.00%)
    1 / 181 (0.55%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 184 (0.54%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 184 (0.00%)
    0 / 181 (0.00%)
    2 / 181 (1.10%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 184 (0.00%)
    0 / 181 (0.00%)
    2 / 181 (1.10%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    1 / 184 (0.54%)
    1 / 181 (0.55%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Liver injury
         subjects affected / exposed
    1 / 184 (0.54%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Diabetic foot
         subjects affected / exposed
    0 / 184 (0.00%)
    1 / 181 (0.55%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 184 (0.54%)
    0 / 181 (0.00%)
    1 / 181 (0.55%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 184 (0.00%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    1 / 184 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervical spinal stenosis
         subjects affected / exposed
    0 / 184 (0.00%)
    0 / 181 (0.00%)
    1 / 181 (0.55%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    0 / 184 (0.00%)
    0 / 181 (0.00%)
    1 / 181 (0.55%)
    1 / 184 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rhabdomyolysis
         subjects affected / exposed
    1 / 184 (0.54%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Carbuncle
         subjects affected / exposed
    0 / 184 (0.00%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    1 / 184 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 184 (0.54%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    1 / 184 (0.54%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 184 (0.00%)
    0 / 181 (0.00%)
    1 / 181 (0.55%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    0 / 184 (0.00%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    1 / 184 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infected skin ulcer
         subjects affected / exposed
    0 / 184 (0.00%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    1 / 184 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 184 (0.00%)
    1 / 181 (0.55%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia pneumococcal
         subjects affected / exposed
    0 / 184 (0.00%)
    1 / 181 (0.55%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    1 / 184 (0.54%)
    0 / 181 (0.00%)
    1 / 181 (0.55%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 184 (0.00%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    1 / 184 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Wound infection
         subjects affected / exposed
    1 / 184 (0.54%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Diabetes mellitus inadequate control
         subjects affected / exposed
    0 / 184 (0.00%)
    0 / 181 (0.00%)
    0 / 181 (0.00%)
    1 / 184 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Oral Semaglutide 3 mg Oral Semaglutide 7 mg Oral Semaglutide 14 mg Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    77 / 184 (41.85%)
    86 / 181 (47.51%)
    100 / 181 (55.25%)
    73 / 184 (39.67%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    3 / 184 (1.63%)
    4 / 181 (2.21%)
    1 / 181 (0.55%)
    11 / 184 (5.98%)
         occurrences all number
    4
    4
    1
    12
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    7 / 184 (3.80%)
    11 / 181 (6.08%)
    10 / 181 (5.52%)
    3 / 184 (1.63%)
         occurrences all number
    8
    12
    11
    3
    Constipation
         subjects affected / exposed
    8 / 184 (4.35%)
    15 / 181 (8.29%)
    12 / 181 (6.63%)
    5 / 184 (2.72%)
         occurrences all number
    8
    16
    13
    6
    Diarrhoea
         subjects affected / exposed
    16 / 184 (8.70%)
    22 / 181 (12.15%)
    26 / 181 (14.36%)
    11 / 184 (5.98%)
         occurrences all number
    19
    26
    40
    15
    Nausea
         subjects affected / exposed
    21 / 184 (11.41%)
    30 / 181 (16.57%)
    41 / 181 (22.65%)
    13 / 184 (7.07%)
         occurrences all number
    23
    34
    60
    19
    Vomiting
         subjects affected / exposed
    11 / 184 (5.98%)
    14 / 181 (7.73%)
    17 / 181 (9.39%)
    7 / 184 (3.80%)
         occurrences all number
    14
    17
    28
    8
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    27 / 184 (14.67%)
    21 / 181 (11.60%)
    18 / 181 (9.94%)
    27 / 184 (14.67%)
         occurrences all number
    42
    32
    29
    35
    Upper respiratory tract infection
         subjects affected / exposed
    8 / 184 (4.35%)
    6 / 181 (3.31%)
    13 / 181 (7.18%)
    13 / 184 (7.07%)
         occurrences all number
    11
    8
    13
    17
    Urinary tract infection
         subjects affected / exposed
    6 / 184 (3.26%)
    5 / 181 (2.76%)
    10 / 181 (5.52%)
    7 / 184 (3.80%)
         occurrences all number
    10
    6
    10
    12
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    8 / 184 (4.35%)
    18 / 181 (9.94%)
    23 / 181 (12.71%)
    2 / 184 (1.09%)
         occurrences all number
    8
    19
    24
    2

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    04 Jan 2017
    New text addressing: 1) Additional eye examinations and additional data collection on diabetic retinopathy. 2) Investigator’s responsibility in ensuring evaluation and management of certain risk factors and complications. 3) Clarification of the criteria for completion, withdrawal and lost to follow-up. 4) Week 26 reporting of trial results. 5) Other minor corrections and clarifications
    23 Jun 2017
    New text addressing the inclusion in the flow chart of the 7-point SMPG profile at visit 18A, and inclusion of an “Eye Examination Category” in section 17.2 “Definition of analysis sets”, and correction of a minor typographical error in section 8.1.5.

    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
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    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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