Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   35489   clinical trials with a EudraCT protocol, of which   5828   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    Efficacy and Safety of Oral Semaglutide versus Liraglutide and versus Placebo in Subjects with Type 2 Diabetes Mellitus. A 52-week randomised, double-blind, active- and placebo-controlled trial.

    Summary
    EudraCT number
    2015-005210-30
    Trial protocol
    SK   LV   HU   DE   CZ   HR  
    Global end of trial date
    30 Mar 2018

    Results information
    Results version number
    v1(current)
    This version publication date
    14 Apr 2019
    First version publication date
    14 Apr 2019
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    NN9924-4224
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02863419
    WHO universal trial number (UTN)
    U1111-1176-6029
    Other trial identifiers
    Japanese trial registration: JapicCTI-163358
    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
    07 Nov 2018
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    19 Aug 2017
    Global end of trial reached?
    Yes
    Global end of trial date
    30 Mar 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 14 mg oral semaglutide versus 1.8 mg liraglutide subcutaneous and versus placebo, all in combination with metformin with or without a sodium-glucose co-transporter-2 (SGLT-2) inhibitor, on glycaemic control in subjects with type 2 diabetes mellitus (T2DM).
    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 on their anti-diabetic background medication (metformin alone or in combination with a SGLT-2 inhibitor) throughout the entire trial.
    Evidence for comparator
    Not applicable.
    Actual start date of recruitment
    10 Aug 2016
    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: 24
    Country: Number of subjects enrolled
    Czech Republic: 30
    Country: Number of subjects enrolled
    Germany: 59
    Country: Number of subjects enrolled
    Croatia: 30
    Country: Number of subjects enrolled
    Hungary: 80
    Country: Number of subjects enrolled
    Japan: 75
    Country: Number of subjects enrolled
    Latvia: 30
    Country: Number of subjects enrolled
    Poland: 73
    Country: Number of subjects enrolled
    Slovakia: 39
    Country: Number of subjects enrolled
    Ukraine: 40
    Country: Number of subjects enrolled
    United States: 179
    Country: Number of subjects enrolled
    South Africa: 52
    Worldwide total number of subjects
    711
    EEA total number of subjects
    341
    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)
    561
    From 65 to 84 years
    150
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    The trial was conducted at 101 sites in 12 countries as follows: Croatia (5), Czech Republic (3), Germany (8), Hungary (9), Japan (9), Latvia (4), Poland (9), Slovakia (5), South Africa (5), Ukraine (3), United Arab Emirates (2), United States (39).

    Pre-assignment
    Screening details
    Not applicable.

    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
    Investigator, Monitor, Carer, Assessor, Subject
    Blinding implementation details
    The trial was double-blinded and the clinical study group and the investigator remained blinded throughout the trial. For both oral semaglutide and liraglutide, the active and corresponding placebo products were visually identical. Furthermore, all semaglutide tablets were visually identical to each other, irrespective of the dose levels.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Oral semaglutide 14 mg
    Arm description
    Subjects were to receive once-daily oral semaglutide tablets for 52 weeks. Subjects started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52). The subjects also received liraglutide placebo once-daily as subcutaneous injection (under the skin) for 52 weeks where they initiated liraglutide placebo at 0.6 mg once-daily, and were dose escalated after 1 week to 1.2 mg, and then dose escalated after 1 week to the recommended maximum dose of 1.8 mg.
    Arm type
    Experimental

    Investigational medicinal product name
    Oral semaglutide 3 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Oral semaglutide 3 mg was administered from week 0 to week 4, as part of dose escalation regimen. The tablet was taken once daily in the morning in a fasting state and at least 30 minutes before the first meal of the day. The trial product could be taken with up to a half a glass of water (approximately 120 mL/4 fluid oz) and was to be swallowed whole and not broken or chewed. Oral medication other than trial product could be taken 30 minutes after administration of trial product

    Investigational medicinal product name
    Oral semaglutide 7 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Oral semaglutide 3 mg was administered from week 4 to week 8, as part of dose escalation regimen. The tablet was taken once daily in the morning in a fasting state and at least 30 minutes before the first meal of the day. The trial product could be taken with up to a half a glass of water (approximately 120 mL/4 fluid oz) and was to be swallowed whole and not broken or chewed. Oral medication other than trial product could be taken 30 minutes after administration of trial product

    Investigational medicinal product name
    Oral semaglutide 14 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Oral semaglutide 14 mg was administered from week 8 to week 52, once daily in the morning in a fasting state and at least 30 minutes before the first meal of the day. The trial product could be taken with up to a half a glass of water (approximately 120 mL/4 fluid oz) and was to be swallowed whole and not broken or chewed. Oral medication other than trial product could be taken 30 minutes after administration of trial product

    Arm title
    Liraglutide 1.8 mg
    Arm description
    Subjects were to receive liraglutide for 52 weeks. Liraglutide was administered once-daily as subcutaneous injection (under the skin) in the abdomen, thigh or upper arm and was taken with or without food, preferably at the same time each day. Subjects initiated liraglutide at 0.6 mg once-daily, and were dose escalated after 1 week to 1.2 mg, and then dose escalated after 1 week to the recommended maximum dose of 1.8 mg. The subjects also received once daily oral semaglutide placebo 14 mg tablets for 52 weeks where they started oral semaglutide placebo at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).
    Arm type
    Active comparator

    Investigational medicinal product name
    Liraglutide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Liraglutide 1.8 mg was administered once-daily as sub-cutaneous injection (under the skin) in the abdomen, thigh or upper arm; it was to be taken with or without food, and preferably at the same time each day.

    Arm title
    Placebo
    Arm description
    Subjects were to receive both semaglutide placebo and liraglutide placebo for 52 weeks. Subjects started semaglutide placebo tablets at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52). Liraglutide placebo was administered once-daily as subcutaneous injection (under the skin) in the abdomen, thigh or upper arm and was taken with or without food, preferably at the same time each day. Subjects initiated liraglutide placebo injection at 0.6 mg once-daily, and were dose escalated after 1 week to 1.2 mg, and then dose escalated after 1 week to the recommended maximum dose of 1.8 mg.
    Arm type
    Placebo

    Investigational medicinal product name
    Oral semaglutide placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Oral semaglutide placebo was administered once daily in the morning in a fasting state and at least 30 minutes before the first meal of the day. The trial product could be taken with up to a half a glass of water (approximately 120 mL/4 fluid oz) and was to be swallowed whole and not broken or chewed. Oral medication other than trial product could be taken 30 minutes after administration of trial product.

    Investigational medicinal product name
    Liraglutide placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Liraglutide placebo was administered once-daily as sub-cutaneous injection (under the skin) in the abdomen, thigh or upper arm; it was to be taken with or without food, and preferably at the same time each day.

    Number of subjects in period 1
    Oral semaglutide 14 mg Liraglutide 1.8 mg Placebo
    Started
    285
    284
    142
    Completed
    277
    274
    134
    Not completed
    8
    10
    8
         Died
             3
             4
             1
         Consent withdrawn by subject
             5
             5
             3
         Lost to follow-up
             -
             1
             4

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Oral semaglutide 14 mg
    Reporting group description
    Subjects were to receive once-daily oral semaglutide tablets for 52 weeks. Subjects started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52). The subjects also received liraglutide placebo once-daily as subcutaneous injection (under the skin) for 52 weeks where they initiated liraglutide placebo at 0.6 mg once-daily, and were dose escalated after 1 week to 1.2 mg, and then dose escalated after 1 week to the recommended maximum dose of 1.8 mg.

    Reporting group title
    Liraglutide 1.8 mg
    Reporting group description
    Subjects were to receive liraglutide for 52 weeks. Liraglutide was administered once-daily as subcutaneous injection (under the skin) in the abdomen, thigh or upper arm and was taken with or without food, preferably at the same time each day. Subjects initiated liraglutide at 0.6 mg once-daily, and were dose escalated after 1 week to 1.2 mg, and then dose escalated after 1 week to the recommended maximum dose of 1.8 mg. The subjects also received once daily oral semaglutide placebo 14 mg tablets for 52 weeks where they started oral semaglutide placebo at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).

    Reporting group title
    Placebo
    Reporting group description
    Subjects were to receive both semaglutide placebo and liraglutide placebo for 52 weeks. Subjects started semaglutide placebo tablets at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52). Liraglutide placebo was administered once-daily as subcutaneous injection (under the skin) in the abdomen, thigh or upper arm and was taken with or without food, preferably at the same time each day. Subjects initiated liraglutide placebo injection at 0.6 mg once-daily, and were dose escalated after 1 week to 1.2 mg, and then dose escalated after 1 week to the recommended maximum dose of 1.8 mg.

    Reporting group values
    Oral semaglutide 14 mg Liraglutide 1.8 mg Placebo Total
    Number of subjects
    285 284 142 711
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    232 220 109 561
        From 65 to 74
    48 56 27 131
        From 75 to 84
    5 8 6 19
        85 and above
    0 0 0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    56 ± 10 56 ± 10 57 ± 10 -
    Sex: Female, Male
    Units: Subjects
        Female
    138 135 68 341
        Male
    147 149 74 370
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    0 1 1 2
        Asian
    39 36 19 94
        Native Hawaiian or Other Pacific Islander
    0 1 0 1
        Black or African American
    12 9 8 29
        White
    208 212 99 519
        More than one race
    3 8 3 14
        Unknown or Not Reported
    23 17 12 52
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    17 18 5 40
        Not Hispanic or Latino
    268 266 137 671
        Unknown or Not Reported
    0 0 0 0
    HbA1c
    Glycosylate haemoglobin
    Units: %-point
        arithmetic mean (standard deviation)
    8.0 ± 0.7 8.0 ± 0.7 7.9 ± 0.7 -
    Body weight
    Units: kg
        arithmetic mean (standard deviation)
    92.9 ± 20.6 95.5 ± 21.9 93.2 ± 20.0 -

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Oral semaglutide 14 mg
    Reporting group description
    Subjects were to receive once-daily oral semaglutide tablets for 52 weeks. Subjects started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52). The subjects also received liraglutide placebo once-daily as subcutaneous injection (under the skin) for 52 weeks where they initiated liraglutide placebo at 0.6 mg once-daily, and were dose escalated after 1 week to 1.2 mg, and then dose escalated after 1 week to the recommended maximum dose of 1.8 mg.

    Reporting group title
    Liraglutide 1.8 mg
    Reporting group description
    Subjects were to receive liraglutide for 52 weeks. Liraglutide was administered once-daily as subcutaneous injection (under the skin) in the abdomen, thigh or upper arm and was taken with or without food, preferably at the same time each day. Subjects initiated liraglutide at 0.6 mg once-daily, and were dose escalated after 1 week to 1.2 mg, and then dose escalated after 1 week to the recommended maximum dose of 1.8 mg. The subjects also received once daily oral semaglutide placebo 14 mg tablets for 52 weeks where they started oral semaglutide placebo at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).

    Reporting group title
    Placebo
    Reporting group description
    Subjects were to receive both semaglutide placebo and liraglutide placebo for 52 weeks. Subjects started semaglutide placebo tablets at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52). Liraglutide placebo was administered once-daily as subcutaneous injection (under the skin) in the abdomen, thigh or upper arm and was taken with or without food, preferably at the same time each day. Subjects initiated liraglutide placebo injection at 0.6 mg once-daily, and were dose escalated after 1 week to 1.2 mg, and then dose escalated after 1 week to the recommended maximum dose of 1.8 mg.

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

    Close Top of page
    End point title
    Change in HbA1c (in-trial observation period) (week 26)
    End point description
    Observed mean change from baseline (week 0) to week 26 in glycosylated haemoglobin. The endpoint was evaluated based on data from the in-trial observation period. In-trial observation period: the time period from when a subject was randomised until the final scheduled visit, including any period after initiation of rescue medication or premature discontinuation of trial product. Full analysis set comprised of all randomised subjects. "Number analysed"=subjects with available data.
    End point type
    Primary
    End point timeframe
    From baseline to week 26
    End point values
    Oral semaglutide 14 mg Liraglutide 1.8 mg Placebo
    Number of subjects analysed
    278
    272
    134
    Units: %-point
        arithmetic mean (standard deviation)
    -1.2 ± 0.9
    -1.1 ± 0.9
    -0.1 ± 0.7
    Statistical analysis title
    Oral semaglutide versus Placebo
    Statistical analysis description
    The endpoint was analysed using an ANCOVA model with treatment, stratification factor and region as categorical fixed effects and baseline HbA1c as covariate. The null hypothesis (H0) and the alternate hypothesis (HA) were: H0: μ ≥0.0%-points against HA: μ <0.0%. (μ denotes mean treatment difference). The analysis was based on a pattern mixture model that used multiple imputation to impute missing week-26 data, assuming that such data were missing at random.
    Comparison groups
    Oral semaglutide 14 mg v Placebo
    Number of subjects included in analysis
    412
    Analysis specification
    Pre-specified
    Analysis type
    superiority [1]
    P-value
    < 0.0001 [2]
    Method
    ANCOVA
    Parameter type
    Treatment difference
    Point estimate
    -1.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.2
         upper limit
    -0.9
    Notes
    [1] - The analysis was based on treatment policy estimand. This hypothesis was controlled for multiplicity. "Subjects in this analysis"=number of subjects with available data; all subjects in the FAS (N=427) with data contributed to the analysis.
    [2] - Unadjusted two-sided p-value for test of no difference from 0.
    Statistical analysis title
    Oral semaglutide versus Liraglutide
    Statistical analysis description
    Change from baseline was analysed using an ANCOVA model with treatment, 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. The hypothesis tested was: H0: μ ≥0.4%-points against HA: μ <0.4%. A value of 0.4% (the non-inferiority margin) was added to imputed values at week 26 for the oral semaglutide treatment arm only.
    Comparison groups
    Oral semaglutide 14 mg v Liraglutide 1.8 mg
    Number of subjects included in analysis
    550
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [3]
    P-value
    < 0.0001 [4]
    Method
    ANCOVA
    Parameter type
    Treatment difference
    Point estimate
    -0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.3
         upper limit
    0
    Notes
    [3] - The analysis was based on treatment policy estimand. This hypothesis was controlled for multiplicity. HbA1c non-inferiority was tested using a non-inferiority margin of 0.4%-points. "Subjects in this analysis"=number of subjects with available data; all subjects in the FAS (N=569) contributed with data to the analysis.
    [4] - Unadjusted two-sided p-value for test of no difference from the non-inferiority margin.
    Statistical analysis title
    Oral semaglutide versus Liraglutide
    Statistical analysis description
    Change from baseline was analysed using an ANCOVA model with treatment, 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. The null hypothesis (H0) and the alternate hypothesis (HA) were: H0: μ ≥0.0%-points against HA: μ <0.0%. (μ denotes mean treatment difference).
    Comparison groups
    Oral semaglutide 14 mg v Liraglutide 1.8 mg
    Number of subjects included in analysis
    550
    Analysis specification
    Pre-specified
    Analysis type
    superiority [5]
    P-value
    = 0.0645 [6]
    Method
    ANCOVA
    Parameter type
    Treatment difference
    Point estimate
    -0.1
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.3
         upper limit
    0
    Notes
    [5] - The analysis was based on treatment policy estimand. This hypothesis was controlled for multiplicity. "Subjects in this analysis"=number of subjects with available data; all subjects in the FAS (N=569) contributed with data 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)

    Close Top of page
    End point title
    Change in HbA1c (on-treatment without rescue medication observation period) (week 26)
    End point description
    Observed mean change from baseline (week 0) to week 26 in glycosylated haemoglobin. The primary endpoint was analysed based on data from the on-treatment without rescue medication observation period. On-treatment without rescue medication observation period: the time period when a subject was on treatment with trial product, excluding any period after initiation of rescue medication. Full analysis set comprised of all randomised subjects. "Number analysed"=subjects with available data.
    End point type
    Primary
    End point timeframe
    From baseline to week 26
    End point values
    Oral semaglutide 14 mg Liraglutide 1.8 mg Placebo
    Number of subjects analysed
    238
    245
    112
    Units: %-points
        arithmetic mean (standard deviation)
    -1.4 ± 0.9
    -1.2 ± 0.9
    -0.1 ± 0.7
    Statistical analysis title
    Oral semaglutide 14 mg vs. Liraglutide
    Statistical analysis description
    Changes from baseline were analysed using a mixed model for repeated measurements model with treatment, strata, and region as categorical fixed effects and baseline value as covariate, all nested within visit, and an unstructured residual covariance matrix. The hypothesis tested was: H0: μ ≥0.4%-points against HA: μ <0.4%. (μ denotes mean treatment difference).
    Comparison groups
    Oral semaglutide 14 mg v Liraglutide 1.8 mg
    Number of subjects included in analysis
    483
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [7]
    P-value
    < 0.0001 [8]
    Method
    Mixed model for repeated measurements
    Parameter type
    Treatment difference
    Point estimate
    -0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.3
         upper limit
    -0.1
    Notes
    [7] - The analysis was based on hypothetical estimand. This hypothesis was not controlled for multiplicity. HbA1c non-inferiority was tested using a non-inferiority margin of 0.4%-points. "Subjects in this analysis"=number of subjects with available data; all subjects in the FAS (N=569) with data contributed to the analysis.
    [8] - Unadjusted two-sided p-value for test of no difference from the non-inferiority margin.
    Statistical analysis title
    Oral semaglutide 14 mg vs. Liraglutide 1.8 mg
    Statistical analysis description
    Changes from baseline were analysed using a mixed model for repeated measurements model with treatment, strata, and region as categorical fixed effects and baseline value as covariate, all nested within visit, and an unstructured residual covariance matrix. The null hypothesis (H0) and the alternate hypothesis (HA) were: H0: μ ≥0.0%-points against HA: μ <0.0%. (μ denotes mean treatment difference).
    Comparison groups
    Oral semaglutide 14 mg v Liraglutide 1.8 mg
    Number of subjects included in analysis
    483
    Analysis specification
    Pre-specified
    Analysis type
    superiority [9]
    P-value
    = 0.0056 [10]
    Method
    Mixed model for repeated measurements
    Parameter type
    Treatment difference
    Point estimate
    -0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.3
         upper limit
    -0.1
    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 (N=569) with data contributed to the analysis.
    [10] - Unadjusted two-sided p-value for test of no difference from 0.
    Statistical analysis title
    Oral semaglutide 14 mg vs. Placebo
    Statistical analysis description
    Changes from baseline were analysed using a mixed model for repeated measurements model with treatment, strata, and region as categorical fixed effects and baseline value as covariate, all nested within visit, and an unstructured residual covariance matrix. The null hypothesis (H0) and the alternate hypothesis (HA) were: H0: μ ≥0.0%-points against HA: μ <0.0%. (μ denotes mean treatment difference).
    Comparison groups
    Oral semaglutide 14 mg v Placebo
    Number of subjects included in analysis
    350
    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
    -1.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.4
         upper limit
    -1
    Notes
    [11] - The 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 (N=427) with data contributed to the analysis.
    [12] - Unadjusted two-sided p-value for test of no difference from 0.

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

    Close Top of page
    End point title
    Change in body weight (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. Results are based on full analysis set comprised of 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 14 mg Liraglutide 1.8 mg Placebo
    Number of subjects analysed
    278
    271
    134
    Units: kg
        arithmetic mean (standard deviation)
    -4.4 ± 4.4
    -3.2 ± 3.7
    -0.6 ± 3.1
    Statistical analysis title
    Oral semaglutide versus Placebo
    Statistical analysis description
    The endpoint was analysed using an ANCOVA model with treatment, stratification factor and region as categorical fixed effects and the baseline body weight value as the covariate. The null hypothesis (H0) and the alternate hypothesis (HA) were: H0: μ ≥0.0 kg against HA: μ <0.0 kg (μ denotes mean treatment difference). The analysis was based on a pattern mixture model that used multiple imputation to impute missing week-26 data, assuming that such data were missing at random.
    Comparison groups
    Oral semaglutide 14 mg v Placebo
    Number of subjects included in analysis
    412
    Analysis specification
    Pre-specified
    Analysis type
    superiority [13]
    P-value
    < 0.0001 [14]
    Method
    ANCOVA
    Parameter type
    Treatment difference
    Point estimate
    -3.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.7
         upper limit
    -3
    Notes
    [13] - The analysis was for the treatment policy estimand. This hypothesis was controlled for multiplicity. Subjects in this analysis=number of subjects with available data; all subjects in the FAS (N=427) contributed with data to the analysis.
    [14] - Unadjusted two-sided p-value for test of no difference from 0.
    Statistical analysis title
    Oral semaglutide versus Liraglutide
    Statistical analysis description
    The endpoint was analysed using an ANCOVA model with treatment, stratification factor and region as categorical fixed effects and the baseline body weight value as the covariate. The null hypothesis (H0) and the alternate hypothesis (HA) were: H0: μ ≥0.0 kg against HA: μ <0.0 kg (μ denotes mean treatment difference). The analysis was based on a pattern mixture model that used multiple imputation to impute missing week-26 data, assuming that such data were missing at random
    Comparison groups
    Oral semaglutide 14 mg v Liraglutide 1.8 mg
    Number of subjects included in analysis
    549
    Analysis specification
    Pre-specified
    Analysis type
    superiority [15]
    P-value
    = 0.0003 [16]
    Method
    ANCOVA
    Parameter type
    Treatment difference
    Point estimate
    -1.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.9
         upper limit
    -0.6
    Notes
    [15] - The analysis was for the treatment policy estimand. This hypothesis was controlled for multiplicity. Subjects in this analysis=number of subjects with available data; all subjects in the FAS (N=569) contributed with data to the analysis
    [16] - Unadjusted two-sided p-value for test of no difference from 0.

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

    Close Top of page
    End point title
    Change in body weight (on-treatment without rescue medication observation period) (week 26)
    End point description
    Observed mean change from baseline (week 0) to week 26 in body weight. The endpoint was evaluated based on data from the on-treatment without rescue medication observation period. Full analysis set comprised of all randomised subjects. "Number analysed"=subjects with available data.
    End point type
    Secondary
    End point timeframe
    From baseline to week 26
    End point values
    Oral semaglutide 14 mg Liraglutide 1.8 mg Placebo
    Number of subjects analysed
    223
    230
    83
    Units: kg
        arithmetic mean (standard deviation)
    -5.0 ± 5.2
    -3.3 ± 4.3
    -1.5 ± 3.3
    Statistical analysis title
    Oral semagltide 14 mg vs. Liraglutide 1.8 mg
    Statistical analysis description
    Changes from baseline were analysed using a mixed model for repeated measurements model with treatment, 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 Liraglutide 1.8 mg
    Number of subjects included in analysis
    453
    Analysis specification
    Pre-specified
    Analysis type
    superiority [17]
    P-value
    < 0.0001 [18]
    Method
    Mixed model for repeated measurements
    Parameter type
    Treatment difference
    Point estimate
    -1.5
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.2
         upper limit
    -0.9
    Notes
    [17] - The analysis was for hypothetical estimand. This hypothesis was not controlled for multiplicity. "Subjects in this analysis"=number of subjects with available data at week 26; all subjects in the FAS (N=569) contributed to the analysis.
    [18] - Unadjusted two sided p-value for test of no difference from 0.
    Statistical analysis title
    Oral semagltide 14 mg vs. Placebo
    Statistical analysis description
    Changes from baseline were analysed using a mixed model for repeated measurements model with treatment, 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
    306
    Analysis specification
    Pre-specified
    Analysis type
    superiority [19]
    P-value
    < 0.0001
    Method
    Mixed model for repeated measurements
    Parameter type
    Treatment difference
    Point estimate
    -4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -4.8
         upper limit
    -3.2
    Notes
    [19] - Analysis was for the hypothetical estimand. This hypothesis was not controlled for multiplicity. Subjects in this analysis"=number of subjects with available data at week 26; all subjects in the FAS (N=427) contributed to the analysis.

    Secondary: Change in HbA1c (week 52)

    Close Top of page
    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. Results are based on full analysis set comprised of 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 14 mg Liraglutide 1.8 mg Placebo
    Number of subjects analysed
    275
    269
    133
    Units: %-point
        arithmetic mean (standard deviation)
    -1.2 ± 1.0
    -0.9 ± 1.0
    -0.1 ± 0.9
    No statistical analyses for this end point

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

    Close Top of page
    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. Results are based on full analysis set comprised of 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 14 mg Liraglutide 1.8 mg Placebo
    Number of subjects analysed
    275
    269
    133
    Units: kg
        arithmetic mean (standard deviation)
    -4.94 ± 6.37
    -3.25 ± 4.33
    -0.99 ± 4.12
    No statistical analyses for this end point

    Secondary: Change in fasting plasma glucose (week 26)

    Close Top of page
    End point title
    Change in fasting plasma glucose (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. Results are based on full analysis set comprised of 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 14 mg Liraglutide 1.8 mg Placebo
    Number of subjects analysed
    276
    269
    133
    Units: mmol/L
        arithmetic mean (standard deviation)
    -2.04 ± 2.28
    -1.91 ± 2.05
    -0.33 ± 2.03
    No statistical analyses for this end point

    Secondary: Change in fasting plasma glucose (week 52)

    Close Top of page
    End point title
    Change in fasting plasma glucose (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. Results are based on full analysis set comprised of 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 14 mg Liraglutide 1.8 mg Placebo
    Number of subjects analysed
    273
    269
    132
    Units: mmol/L
        arithmetic mean (standard deviation)
    -1.91 ± 2.41
    -1.54 ± 2.41
    -0.66 ± 1.99
    No statistical analyses for this end point

    Secondary: Achieved HbA1c < 7.0 % (53 mmol/mol) American Diabetes Association target (yes/no) (week 26)

    Close Top of page
    End point title
    Achieved HbA1c < 7.0 % (53 mmol/mol) American Diabetes Association target (yes/no) (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. Results are based on full analysis set comprised of all randomised subjects. "Number of subjects analysed"=subjects with available data.
    End point type
    Secondary
    End point timeframe
    At week 26
    End point values
    Oral semaglutide 14 mg Liraglutide 1.8 mg Placebo
    Number of subjects analysed
    278
    272
    134
    Units: percentage
    number (not applicable)
        Yes
    67.6
    61.8
    14.2
        No
    32.4
    38.2
    85.8
    No statistical analyses for this end point

    Secondary: Achieved HbA1c < 7.0 % (53 mmol/mol) American Diabetes Association target (yes/no) (week 52)

    Close Top of page
    End point title
    Achieved HbA1c < 7.0 % (53 mmol/mol) American Diabetes Association target (yes/no) (week 52)
    End point description
    Number of subjects achieving HbA1c < 7.0 % (53 mmol/mol) according to American Diabetes Association (ADA) target, at week 52. The endpoint was evaluated based on data from the in-trial observation period. Results are based on full analysis set comprised of all randomised subjects. "Number of subjects analysed"=subjects with available data.
    End point type
    Secondary
    End point timeframe
    At week 52
    End point values
    Oral semaglutide 14 mg Liraglutide 1.8 mg Placebo
    Number of subjects analysed
    275
    269
    133
    Units: percentage
    number (not applicable)
        Yes
    60.7
    55.0
    15.0
        No
    39.3
    45.0
    85.0
    No statistical analyses for this end point

    Secondary: Number of treatment-emergent adverse events

    Close Top of page
    End point title
    Number of treatment-emergent adverse events
    End point description
    A treatment-emergent adverse event (TEAE) is defined as an adverse event with onset in the on-treatment observation period (the time period where subjects are considered treated with trial product). The safety analysis set (SAS) included all randomised subjects who received at least one dose of trial product. "Number of subjects analysed"=subjects with available data.
    End point type
    Secondary
    End point timeframe
    During exposure to trial product, assessed up to approximately 57 weeks
    End point values
    Oral semaglutide 14 mg Liraglutide 1.8 mg Placebo
    Number of subjects analysed
    285
    284
    142
    Units: Events
    973
    927
    300
    No statistical analyses for this end point

    Secondary: Number of treatment-emergent severe or blood glucose-confirmed symptomatic hypoglycaemic episodes

    Close Top of page
    End point title
    Number of treatment-emergent severe or blood glucose-confirmed symptomatic hypoglycaemic episodes
    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 American Diabetes Association classification or blood glucose-confirmed by a plasma glucose value <3.1 mmol/L (56mg/dL) with symptoms consistent with hypoglycaemia. The safety analysis set (SAS) included all randomised subjects who received at least one dose of trial product. "Number of subjects analysed"=subjects with available data.
    End point type
    Secondary
    End point timeframe
    During exposure to trial product, assessed up to approximately 57 weeks
    End point values
    Oral semaglutide 14 mg Liraglutide 1.8 mg Placebo
    Number of subjects analysed
    285
    284
    142
    Units: Episodes
    2
    9
    3
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    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
    Evaluation of safety was based on safety analysis set (SAS) which comprised of all randomised subjects who received at least one dose of trial product. AEs with onset during the on-treatment observation period (the period when subjects were exposed to trial product) were considered treatment-emergent.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    20
    Reporting groups
    Reporting group title
    Oral Semaglutide 14 mg
    Reporting group description
    Subjects were to receive once-daily oral semaglutide tablets for 52 weeks. Subjects started oral semaglutide at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52). The subjects also received liraglutide placebo once-daily as subcutaneous injection (under the skin) for 52 weeks where they initiated liraglutide placebo at 0.6 mg once-daily, and were dose escalated after 1 week to 1.2 mg, and then dose escalated after 1 week to the recommended maximum dose of 1.8 mg.

    Reporting group title
    Liraglutide 1.8 mg
    Reporting group description
    Subjects were to receive liraglutide for 52 weeks. Liraglutide was administered once-daily as subcutaneous injection (under the skin) in the abdomen, thigh or upper arm and was taken with or without food, preferably at the same time each day. Subjects initiated liraglutide at 0.6 mg once-daily, and were dose escalated after 1 week to 1.2 mg, and then dose escalated after 1 week to the recommended maximum dose of 1.8 mg. The subjects also received once daily oral semaglutide placebo 14 mg tablets for 52 weeks where they started oral semaglutide placebo at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52).

    Reporting group title
    Placebo
    Reporting group description
    Subjects were to receive both semaglutide placebo and liraglutide placebo for 52 weeks. Subjects started semaglutide placebo tablets at 3 mg and were dose escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8, 14 mg from week 8 to week 52). Liraglutide placebo was administered once-daily as subcutaneous injection (under the skin) in the abdomen, thigh or upper arm and was taken with or without food, preferably at the same time each day. Subjects initiated liraglutide placebo injection at 0.6 mg once-daily, and were dose escalated after 1 week to 1.2 mg, and then dose escalated after 1 week to the recommended maximum dose of 1.8 mg.

    Serious adverse events
    Oral Semaglutide 14 mg Liraglutide 1.8 mg Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    31 / 285 (10.88%)
    22 / 284 (7.75%)
    15 / 142 (10.56%)
         number of deaths (all causes)
    3
    4
    1
         number of deaths resulting from adverse events
    0
    0
    0
    Vascular disorders
    Diabetic vascular disorder
         subjects affected / exposed
    0 / 285 (0.00%)
    1 / 284 (0.35%)
    0 / 142 (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 / 285 (0.00%)
    0 / 284 (0.00%)
    1 / 142 (0.70%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    0 / 285 (0.00%)
    1 / 284 (0.35%)
    0 / 142 (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
    Varicose vein
         subjects affected / exposed
    0 / 285 (0.00%)
    0 / 284 (0.00%)
    1 / 142 (0.70%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Hospitalisation
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    0 / 142 (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
    Thyroidectomy
         subjects affected / exposed
    0 / 285 (0.00%)
    1 / 284 (0.35%)
    0 / 142 (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
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Benign neoplasm of thyroid gland
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    0 / 142 (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
    Colon adenoma
         subjects affected / exposed
    0 / 285 (0.00%)
    1 / 284 (0.35%)
    0 / 142 (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
    Invasive ductal breast carcinoma
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    0 / 142 (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
    Lung adenocarcinoma
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    0 / 142 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Oral fibroma
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    0 / 142 (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
    Ovarian cancer metastatic
         subjects affected / exposed
    0 / 285 (0.00%)
    1 / 284 (0.35%)
    0 / 142 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Pancreatic carcinoma
         subjects affected / exposed
    0 / 285 (0.00%)
    1 / 284 (0.35%)
    0 / 142 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Papillary thyroid cancer
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    0 / 142 (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
    Parathyroid tumour benign
         subjects affected / exposed
    0 / 285 (0.00%)
    1 / 284 (0.35%)
    0 / 142 (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
    Thyroid cancer metastatic
         subjects affected / exposed
    0 / 285 (0.00%)
    1 / 284 (0.35%)
    0 / 142 (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
    General disorders and administration site conditions
    Death
         subjects affected / exposed
    0 / 285 (0.00%)
    1 / 284 (0.35%)
    0 / 142 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    0 / 142 (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
    Menometrorrhagia
         subjects affected / exposed
    0 / 285 (0.00%)
    0 / 284 (0.00%)
    1 / 142 (0.70%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Accidental overdose
         subjects affected / exposed
    0 / 285 (0.00%)
    0 / 284 (0.00%)
    1 / 142 (0.70%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Ankle fracture
         subjects affected / exposed
    0 / 285 (0.00%)
    1 / 284 (0.35%)
    0 / 142 (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
    Meniscus injury
         subjects affected / exposed
    1 / 285 (0.35%)
    1 / 284 (0.35%)
    0 / 142 (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
    Muscle rupture
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    0 / 142 (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
    Spinal compression fracture
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    0 / 142 (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
    Subdural haematoma
         subjects affected / exposed
    0 / 285 (0.00%)
    1 / 284 (0.35%)
    0 / 142 (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
    Tibia fracture
         subjects affected / exposed
    0 / 285 (0.00%)
    1 / 284 (0.35%)
    0 / 142 (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
    Investigations
    Hepatic enzyme increased
         subjects affected / exposed
    0 / 285 (0.00%)
    1 / 284 (0.35%)
    0 / 142 (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
    Investigation
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    0 / 142 (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
    Lipase increased
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    0 / 142 (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
    Weight decreased
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    0 / 142 (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
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    1 / 142 (0.70%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    1 / 285 (0.35%)
    1 / 284 (0.35%)
    0 / 142 (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
    Atrial flutter
         subjects affected / exposed
    0 / 285 (0.00%)
    0 / 284 (0.00%)
    1 / 142 (0.70%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block second degree
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    0 / 142 (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 chronic
         subjects affected / exposed
    0 / 285 (0.00%)
    1 / 284 (0.35%)
    0 / 142 (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
    Coronary artery disease
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    0 / 142 (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
    Coronary artery occlusion
         subjects affected / exposed
    0 / 285 (0.00%)
    1 / 284 (0.35%)
    0 / 142 (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
    Myocardial infarction
         subjects affected / exposed
    2 / 285 (0.70%)
    1 / 284 (0.35%)
    0 / 142 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    Ventricular extrasystoles
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    0 / 142 (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
    Congenital, familial and genetic disorders
    Respiratory tract malformation
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    0 / 142 (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, thoracic and mediastinal disorders
    Epistaxis
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    1 / 142 (0.70%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Aphasia
         subjects affected / exposed
    0 / 285 (0.00%)
    0 / 284 (0.00%)
    1 / 142 (0.70%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Carpal tunnel syndrome
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    0 / 142 (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
    Cerebellar syndrome
         subjects affected / exposed
    0 / 285 (0.00%)
    0 / 284 (0.00%)
    1 / 142 (0.70%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    0 / 142 (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
    Cerebrovascular disorder
         subjects affected / exposed
    0 / 285 (0.00%)
    0 / 284 (0.00%)
    1 / 142 (0.70%)
         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 neuropathy
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    0 / 142 (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
    Dizziness
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    0 / 142 (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
    Facial paresis
         subjects affected / exposed
    0 / 285 (0.00%)
    0 / 284 (0.00%)
    1 / 142 (0.70%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    0 / 285 (0.00%)
    0 / 284 (0.00%)
    1 / 142 (0.70%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hemiparesis
         subjects affected / exposed
    0 / 285 (0.00%)
    0 / 284 (0.00%)
    1 / 142 (0.70%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    0 / 285 (0.00%)
    0 / 284 (0.00%)
    1 / 142 (0.70%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sciatica
         subjects affected / exposed
    0 / 285 (0.00%)
    0 / 284 (0.00%)
    1 / 142 (0.70%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    0 / 142 (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
    Trigeminal neuralgia
         subjects affected / exposed
    0 / 285 (0.00%)
    1 / 284 (0.35%)
    0 / 142 (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
    Eye disorders
    Ophthalmic vein thrombosis
         subjects affected / exposed
    0 / 285 (0.00%)
    1 / 284 (0.35%)
    0 / 142 (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
    Ear and labyrinth disorders
    Vertigo positional
         subjects affected / exposed
    0 / 285 (0.00%)
    0 / 284 (0.00%)
    1 / 142 (0.70%)
         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 disorders
    Duodenal ulcer
         subjects affected / exposed
    0 / 285 (0.00%)
    0 / 284 (0.00%)
    1 / 142 (0.70%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    0 / 142 (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
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 285 (0.00%)
    0 / 284 (0.00%)
    1 / 142 (0.70%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hiatus hernia
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    0 / 142 (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
    Large intestine polyp
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    0 / 142 (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
    Nausea
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    0 / 142 (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
    Vomiting
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    0 / 142 (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
    Renal and urinary disorders
    Nephrolithiasis
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    0 / 142 (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
    Renal failure
         subjects affected / exposed
    0 / 285 (0.00%)
    1 / 284 (0.35%)
    0 / 142 (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
    Ureterolithiasis
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    0 / 142 (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
    Hepatobiliary disorders
    Cholecystitis
         subjects affected / exposed
    0 / 285 (0.00%)
    1 / 284 (0.35%)
    0 / 142 (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
    Cholelithiasis
         subjects affected / exposed
    0 / 285 (0.00%)
    1 / 284 (0.35%)
    0 / 142 (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
    Drug-induced liver injury
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    0 / 142 (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
    Hepatic haematoma
         subjects affected / exposed
    0 / 285 (0.00%)
    1 / 284 (0.35%)
    0 / 142 (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
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 285 (0.00%)
    0 / 284 (0.00%)
    1 / 142 (0.70%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    0 / 285 (0.00%)
    1 / 284 (0.35%)
    0 / 142 (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
    Bursitis
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    0 / 142 (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
    Intervertebral disc protrusion
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    0 / 142 (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
    Ligamentitis
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    0 / 142 (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
    Osteoarthritis
         subjects affected / exposed
    0 / 285 (0.00%)
    2 / 284 (0.70%)
    0 / 142 (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
    Spinal osteoarthritis
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    0 / 142 (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
    Tendon disorder
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    0 / 142 (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
    Endocrine disorders
    Thyroid mass
         subjects affected / exposed
    0 / 285 (0.00%)
    1 / 284 (0.35%)
    0 / 142 (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
    Metabolism and nutrition disorders
    Cachexia
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    0 / 142 (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
    Infections and infestations
    Cellulitis
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    0 / 142 (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
    Chronic sinusitis
         subjects affected / exposed
    0 / 285 (0.00%)
    0 / 284 (0.00%)
    1 / 142 (0.70%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    0 / 142 (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
    Herpes zoster
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    0 / 142 (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
    Otitis media
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    0 / 142 (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
    Postoperative wound infection
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    0 / 142 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    0 / 142 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 285 (0.35%)
    0 / 284 (0.00%)
    0 / 142 (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
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Oral Semaglutide 14 mg Liraglutide 1.8 mg Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    148 / 285 (51.93%)
    120 / 284 (42.25%)
    47 / 142 (33.10%)
    Investigations
    Blood glucose increased
         subjects affected / exposed
    0 / 285 (0.00%)
    2 / 284 (0.70%)
    9 / 142 (6.34%)
         occurrences all number
    0
    2
    10
    Nervous system disorders
    Headache
         subjects affected / exposed
    27 / 285 (9.47%)
    17 / 284 (5.99%)
    8 / 142 (5.63%)
         occurrences all number
    33
    24
    12
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    16 / 285 (5.61%)
    6 / 284 (2.11%)
    3 / 142 (2.11%)
         occurrences all number
    16
    6
    3
    Constipation
         subjects affected / exposed
    22 / 285 (7.72%)
    11 / 284 (3.87%)
    4 / 142 (2.82%)
         occurrences all number
    23
    12
    4
    Diarrhoea
         subjects affected / exposed
    43 / 285 (15.09%)
    31 / 284 (10.92%)
    11 / 142 (7.75%)
         occurrences all number
    59
    42
    11
    Dyspepsia
         subjects affected / exposed
    16 / 285 (5.61%)
    12 / 284 (4.23%)
    0 / 142 (0.00%)
         occurrences all number
    26
    13
    0
    Nausea
         subjects affected / exposed
    55 / 285 (19.30%)
    51 / 284 (17.96%)
    5 / 142 (3.52%)
         occurrences all number
    69
    67
    5
    Vomiting
         subjects affected / exposed
    24 / 285 (8.42%)
    13 / 284 (4.58%)
    3 / 142 (2.11%)
         occurrences all number
    28
    24
    3
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    11 / 285 (3.86%)
    17 / 284 (5.99%)
    5 / 142 (3.52%)
         occurrences all number
    13
    19
    6
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    16 / 285 (5.61%)
    20 / 284 (7.04%)
    0 / 142 (0.00%)
         occurrences all number
    17
    23
    0
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    41 / 285 (14.39%)
    37 / 284 (13.03%)
    15 / 142 (10.56%)
         occurrences all number
    60
    59
    18

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    15 Dec 2016
    Key changes: 1. Introduction of additional eye examinations and additional data collection on diabetic retinopathy 2. Added bicarbonate as a part of the biochemistry laboratory assessment 3. Added text to highlight investigator’s responsibility in ensuring evaluation and management of certain risk factors and complications 4. Clarification of the criteria for completion, withdrawal and lost to follow-up 5. Other minor corrections and clarifications

    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
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2019 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA