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    Clinical Trial Results:
    Effect of semaglutide on functional capacity in patients with type 2 diabetes and peripheral artery disease

    Summary
    EudraCT number
    		 2019-003399-38
    Trial protocol
    		 DE   AT   HU   NO   BE   DK   LV  
    Global end of trial date
    12 Jul 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    24 Jul 2025
    First version publication date
    24 Jul 2025
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    NN9535-4533
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04560998
    WHO universal trial number (UTN)
    		 U1111-1238-7071
    Other trial identifiers
    		 Japanese trial registration number: jRCT2031200141
    Sponsors
    Sponsor organisation name
    Novo Nordisk A/S
    Sponsor organisation address
    Novo Alle, Bagsvaerd, Denmark, 2880
    Public contact
    Clinical Reporting Office (2834), Novo Nordisk A/S, clinicaltrials@novonordisk.com
    Scientific contact
    Clinical Reporting Office (2834), 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
    02 Sep 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    12 Jul 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective is to demonstrate the effect of subcutaneous (s.c., under the skin) semaglutide 1 mg once-weekly on walking ability compared with placebo, both added to standard-of-care, in patients with type 2 diabetes (T2D) and peripheral arterial disease (PAD) with intermittent claudication.
    Protection of trial subjects
    The study was conducted in accordance with the Declaration of Helsinki and International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Good Clinical Practice, including archiving of essential documents.
    Background therapy
    		 Not applicable
    Evidence for comparator
    		 Not applicable
    Actual start date of recruitment
    01 Oct 2020
    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
    Austria: 5
    Country: Number of subjects enrolled
    Belgium: 30
    Country: Number of subjects enrolled
    Canada: 61
    Country: Number of subjects enrolled
    China: 18
    Country: Number of subjects enrolled
    Czechia: 27
    Country: Number of subjects enrolled
    Germany: 23
    Country: Number of subjects enrolled
    Denmark: 44
    Country: Number of subjects enrolled
    Spain: 38
    Country: Number of subjects enrolled
    Greece: 66
    Country: Number of subjects enrolled
    Hungary: 61
    Country: Number of subjects enrolled
    India: 33
    Country: Number of subjects enrolled
    Japan: 79
    Country: Number of subjects enrolled
    Latvia: 35
    Country: Number of subjects enrolled
    Malaysia: 33
    Country: Number of subjects enrolled
    Norway: 11
    Country: Number of subjects enrolled
    Poland: 100
    Country: Number of subjects enrolled
    Sweden: 8
    Country: Number of subjects enrolled
    Thailand: 30
    Country: Number of subjects enrolled
    Taiwan: 38
    Country: Number of subjects enrolled
    United States: 52
    Worldwide total number of subjects
    792
    EEA total number of subjects
    448
    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)
    285
    From 65 to 84 years
    499
    85 years and over
    8

    Subject disposition

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    Recruitment
    Recruitment details
    		 The trial was conducted at 129 sites in 21 countries.

    Pre-assignment
    Screening details
    		 Participants were randomized in a 1:1 ratio to receive treatment with either semaglutide or placebo as an adjunct to standard-of-care.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Semaglutide
    Arm description
    		 Participants received once-weekly (OW) subcutaneous injection (s. c.) of semaglutide for 52 weeks. Participants received a dose of 0.25 milligrams (mg) from week 0 to week 4, then the dose was increased to 0.5 mg from week 4 to week 8. From week 8 to week 52, the dosage was 1.0 mg.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Semaglutide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Once-weekly subcutaneous injection of semaglutide was administered for 52 weeks

    Arm title
    		 Placebo
    Arm description
    		 Participants received once-weekly (OW) subcutaneous injection (s. c.) of placebo matched for semaglutide for 52 weeks.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Once-weekly subcutaneous injection of placebo matched for semaglutide was administered for 52 weeks.

    Number of subjects in period 1
    		Semaglutide Placebo
    Started
    396
    396
    Full analysis set
    396
    396
    Safety analysis set
    396
    395
    Completed
    366
    379
    Not completed
    30
    17
         Physician decision
    4
    -
         Consent withdrawn by subject
    18
    12
         Lost to follow-up
    8
    5

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Semaglutide
    Reporting group description
    		 Participants received once-weekly (OW) subcutaneous injection (s. c.) of semaglutide for 52 weeks. Participants received a dose of 0.25 milligrams (mg) from week 0 to week 4, then the dose was increased to 0.5 mg from week 4 to week 8. From week 8 to week 52, the dosage was 1.0 mg.

    Reporting group title
    Placebo
    Reporting group description
    		 Participants received once-weekly (OW) subcutaneous injection (s. c.) of placebo matched for semaglutide for 52 weeks.

    Reporting group values
    		 Semaglutide Placebo Total
    Number of subjects
    		 396 396 792
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 152 133 285
        From 65 years
    		 244 263 507
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 66.2 ( 9.71 ) 67.0 ( 8.96 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 107 88 195
        Male
    		 289 308 597

    End points

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    End points reporting groups
    Reporting group title
    Semaglutide
    Reporting group description
    		 Participants received once-weekly (OW) subcutaneous injection (s. c.) of semaglutide for 52 weeks. Participants received a dose of 0.25 milligrams (mg) from week 0 to week 4, then the dose was increased to 0.5 mg from week 4 to week 8. From week 8 to week 52, the dosage was 1.0 mg.

    Reporting group title
    Placebo
    Reporting group description
    		 Participants received once-weekly (OW) subcutaneous injection (s. c.) of placebo matched for semaglutide for 52 weeks.

    Primary: Change in maximum walking distance on a constant load treadmill test

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    End point title
    		 Change in maximum walking distance on a constant load treadmill test
    End point description
    Constant-load treadmill test with fixed speed (3.2 km/h, 2 mph), fixed inclination (12%) is a standardised method for functional assessment of patients with peripheral artery disease. Participants continue on treadmill after indicating onset of pain and should continue as long as possible until pain limits further activity. This distance is the maximum walking distance. Endpoint was evaluated based on data from in-study observation period. In-study observation period is defined as period from date of randomisation to one of the following dates, whichever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete the trial and did not withdraw consent), date of death. Full Analysis Set (FAS). Overall Number of Participants Analyzed = number of participants with available data for this endpoint.
    End point type
    Primary
    End point timeframe
    From baseline (week 0) to end of treatment (week 52)
    End point values
    		 Semaglutide Placebo
    Number of subjects analysed
    338
    345
    Units: Ratio of maximum walking distance
        median (inter-quartile range (Q1-Q3))
    1.21 (0.95 to 1.55)
    1.08 (0.86 to 1.36)
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Semaglutide v Placebo
    Number of subjects included in analysis
    683
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0004
    Method
    		 Wilcoxon (Mann-Whitney)
    Parameter type
    		 The Hodges-Lehmann estimate
    Point estimate
    1.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.056
         upper limit
    		 1.211

    Secondary: Follow-up change in maximum walking distance on a constant load treadmill test

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    End point title
    		 Follow-up change in maximum walking distance on a constant load treadmill test
    End point description
    Constant-load treadmill test with fixed speed (3.2 km/h, 2 mph), fixed inclination (12%) is a standardised method for functional assessment of patients with peripheral artery disease. Participants continue on the treadmill after indicating onset of pain and should continue as long as possible until pain limits further activity. This distance is maximum walking distance. Endpoint measure was evaluated based on data from in-study observation period. In-study observation period is defined as the period from date of randomisation to one of following dates, which-ever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete the trial and did not withdraw consent), date of death. Full Analysis Set (FAS). Overall Number of Participants Analyzed = number of participants with available data for this endpoint.
    End point type
    Secondary
    End point timeframe
    From baseline (week 0) to end of follow-up (week 57)
    End point values
    		 Semaglutide Placebo
    Number of subjects analysed
    329
    333
    Units: Ratio of maximum walking distance
        median (inter-quartile range (Q1-Q3))
    1.16 (0.92 to 1.48)
    1.10 (0.87 to 1.40)
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Semaglutide v Placebo
    Number of subjects included in analysis
    662
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.038
    Method
    		 Wilcoxon (Mann-Whitney)
    Parameter type
    		 The Hodges-Lehmann estimate
    Point estimate
    1.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.004
         upper limit
    		 1.156

    Secondary: Change in Vascular Quality of Life Questionnaire-6 (VascuQoL-6) score

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    End point title
    		 Change in Vascular Quality of Life Questionnaire-6 (VascuQoL-6) score
    End point description
    VascuQoL-6 is a peripheral artery disease-specific questionnaire with 6 items covering social, emotional, functional, pain/symptom-related aspects of the patient´s overall quality of life. Each item has a 4-point response scale (where 1 = worst score and 4 = best score). Endpoint analysed is the total score (range: 6-24) generated by summing the scores from all items. Higher score indicates better health status. Endpoint was evaluated based on data from in-study observation period. In-study observation period is defined as the period from date of randomisation to one of following dates, whichever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete trial and did not withdraw consent), date of death. Full Analysis Set (FAS). Overall Number of Participants Analyzed = number of participants with available data for this endpoint.
    End point type
    Secondary
    End point timeframe
    From baseline (week 0) to end of treatment (week 52)
    End point values
    		 Semaglutide Placebo
    Number of subjects analysed
    362
    362
    Units: Scores on a scale
        median (inter-quartile range (Q1-Q3))
    2.0 (0.00 to 4.00)
    1.0 (-1.00 to 4.00)
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Semaglutide v Placebo
    Number of subjects included in analysis
    724
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0108
    Method
    		 Wilcoxon (Mann-Whitney)
    Parameter type
    		 The Hodges-Lehmann estimate
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.478
         upper limit
    		 1.518

    Secondary: Follow-up change in pain-free walking distance on a constant load treadmill test

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    End point title
    		 Follow-up change in pain-free walking distance on a constant load treadmill test
    End point description
    The constant-load treadmill test with fixed speed (3.2 km/h, 2 mph), fixed inclination (12%) is a standardised method for functional assessment of patients with peripheral artery disease. Participants are instructed to when pain starts in either leg and to continue on the treadmill without stop-ping at this stage. Distance walked is pain-free walking distance. Endpoint was evaluated based on data from in-study observation period. In-study observation period is defined as the period from date of randomisation to one of the following dates, whichever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete the trial and did not withdraw consent), date of death. Full Analysis Set (FAS). Overall Number of Participants Analyzed = number of participants with available data for this endpoint.
    End point type
    Secondary
    End point timeframe
    From baseline (week 0) to end of follow-up (week 57)
    End point values
    		 Semaglutide Placebo
    Number of subjects analysed
    329
    333
    Units: Ratio of pain-free walking distance
        median (inter-quartile range (Q1-Q3))
    1.18 (0.92 to 1.59)
    1.10 (0.83 to 1.48)
    No statistical analyses for this end point

    Secondary: Change in pain-free walking distance on a constant load treadmill test

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    End point title
    		 Change in pain-free walking distance on a constant load treadmill test
    End point description
    The constant-load treadmill test with fixed speed (3.2 km/h, 2 mph), fixed inclination (12%) is a standardised method for functional assessment of patients with peripheral artery disease. Participants are instructed to when pain starts in either leg and to continue on the treadmill without stopping at this stage. Distance walked is pain-free walking distance. Endpoint was evaluated based on data from in-study observation period. In-study observation period is defined as period from date of randomisation to one of following dates, whichever comes first: date of follow-up visit, date when participant withdrew consent, date of last contact with participant for participants who were lost to follow-up (participant did not complete the trial and did not withdraw consent), date of death. Full Analysis Set (FAS). Overall Number of Participants Analyzed = number of participants with available data for this endpoint.
    End point type
    Secondary
    End point timeframe
    From baseline (week 0) to end of treatment (week 52)
    End point values
    		 Semaglutide Placebo
    Number of subjects analysed
    338
    344
    Units: Ratio of pain-free walking distance
        median (inter-quartile range (Q1-Q3))
    1.21 (0.92 to 1.52)
    1.10 (0.86 to 1.44)
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Semaglutide v Placebo
    Number of subjects included in analysis
    682
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0046
    Method
    		 Wilcoxon (Mann-Whitney)
    Parameter type
    		 The Hodges-Lehmann Estimate
    Point estimate
    1.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.033
         upper limit
    		 1.197

    Secondary: Change in body weight

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    End point title
    		 Change in body weight
    End point description
    Change in body weight from baseline to week 52 in kilogram (kg) is presented. The endpoint is evaluated based on the on-treatment without rescue treatment observation period. This period includes assessments and events for the time period where participants were exposed to trial product and before rescue treatment (medication or revascularisation procedure). Full Analysis Set (FAS). Overall Number of Participants Analyzed = number of participants with available data for this endpoint.
    End point type
    Secondary
    End point timeframe
    From baseline (week 0) to end of treatment (week 52)
    End point values
    		 Semaglutide Placebo
    Number of subjects analysed
    310
    318
    Units: Kilogram (kg)
        arithmetic mean (standard deviation)
    -5.2 ( 4.8 )
    -1.2 ( 4.2 )
    No statistical analyses for this end point

    Secondary: Change in Glycosylated Haemoglobin (HbA1c)

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    End point title
    		 Change in Glycosylated Haemoglobin (HbA1c)
    End point description
    Change in HbA1c from baseline to week 52 in percentage-point is presented. The endpoint is evaluated based on the on treatment without rescue treatment observation period. This period includes assessments and events for the time period where participants were exposed to trial product and before rescue treatment (medication or revascularisation procedure). Full Analysis Set (FAS). Overall Number of Participants Analyzed = number of participants with available data for this endpoint.
    End point type
    Secondary
    End point timeframe
    From baseline (week 0) to end of treatment (week 52)
    End point values
    		 Semaglutide Placebo
    Number of subjects analysed
    304
    311
    Units: Percentage-point of HbA1c
        arithmetic mean (standard deviation)
    -0.8 ( 1.1 )
    0.2 ( 1.1 )
    No statistical analyses for this end point

    Secondary: Change in Low-density lipoprotein (LDL)-cholesterol

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    End point title
    		 Change in Low-density lipoprotein (LDL)-cholesterol
    End point description
    Change in LDL-cholesterol from baseline to week 52 is presented as ratio to baseline. The endpoint is evaluated based on the on-treatment without rescue treatment observation period. This period includes assessments and events for the time period where participants were exposed to trial product and before rescue treatment (medication or revascularisation procedure). Full Analysis Set (FAS). Overall Number of Participants Analyzed = number of participants with available data for this endpoint.
    End point type
    Secondary
    End point timeframe
    From baseline (week 0) to end of treatment (week 52)
    End point values
    		 Semaglutide Placebo
    Number of subjects analysed
    294
    296
    Units: Ratio of LDL
        geometric mean (geometric coefficient of variation)
    0.99 ( 38.37 )
    1.03 ( 42.27 )
    No statistical analyses for this end point

    Secondary: Change in total cholesterol

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    End point title
    		 Change in total cholesterol
    End point description
    Change in total cholesterol from baseline to week 52 is presented as ratio to baseline. The endpoint is evaluated based on the on-treatment without rescue treatment observation period. This period includes assessments and events for the time period where participants were exposed to trial product and before rescue treatment (medication or revascularisation procedure). Full Analysis Set (FAS). Overall Number of Participants Analyzed = number of participants with available data for this endpoint.
    End point type
    Secondary
    End point timeframe
    From baseline (week 0) to end of treatment (week 52)
    End point values
    		 Semaglutide Placebo
    Number of subjects analysed
    305
    312
    Units: Ratio of total cholesterol
        geometric mean (geometric coefficient of variation)
    0.96 ( 20.18 )
    1.00 ( 19.88 )
    No statistical analyses for this end point

    Secondary: Change in systolic blood pressure

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    End point title
    		 Change in systolic blood pressure
    End point description
    Change in systolic blood pressure from baseline to week 52 is presented. The endpoint measure is evaluated based on the on treatment without rescue treatment observation period. This period includes assessments and events for the time period where participants were exposed to trial product and before rescue treatment (medication or revascularisation procedure). Full Analysis Set (FAS). Overall Number of Participants Analyzed = number of participants with available data for this endpoint.
    End point type
    Secondary
    End point timeframe
    From baseline (week 0) to end of treatment (week 52)
    End point values
    		 Semaglutide Placebo
    Number of subjects analysed
    310
    319
    Units: Millimetre of mercury (mmHg)
        arithmetic mean (standard deviation)
    -4 ( 15 )
    -1 ( 18 )
    No statistical analyses for this end point

    Secondary: Change in Ankle–Brachial Index (ABI)

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    End point title
    		 Change in Ankle–Brachial Index (ABI)
    End point description
    Change in ABI from baseline to week 52 is presented. ABI is calculated as a ratio of the higher ankle systolic pressure to the higher systolic pressure measured in both arms. ABI is measured at both left and right leg and the analysis endpoint is defined as the lower of the two indices. An ABI between 1.0 to 1.4 is considered the normal range. An ABI between 0.90 to 0.99 is considered borderline. An ABI less than 0.90 indicates peripheral artery disease (PAD). The endpoint is evaluated based on the on-treatment without rescue treatment observation period. This period includes assessments and events for the time period where participants were exposed to trial product and before rescue treatment (medication or revascularisation procedure). Full Analysis Set (FAS). Overall Number of Participants Analyzed = number of participants with available data for this endpoint.
    End point type
    Secondary
    End point timeframe
    From screening (week -2) to end of treatment (week 52)
    End point values
    		 Semaglutide Placebo
    Number of subjects analysed
    306
    315
    Units: Ratio of ABI
        geometric mean (geometric coefficient of variation)
    1.06 ( 34.0 )
    1.02 ( 19.6 )
    No statistical analyses for this end point

    Secondary: Change in High density lipoprotein (HDL)-cholesterol

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    End point title
    		 Change in High density lipoprotein (HDL)-cholesterol
    End point description
    Change in HDL-cholesterol from baseline to week 52 is presented as ratio to baseline. The endpoint is evaluated based on the on-treatment without rescue treatment observation period. This period includes assessments and events for the time period where participants were exposed to trial product and before rescue treatment (medication or revascularisation procedure). Full Analysis Set (FAS). Overall Number of Participants Analyzed = number of participants with available data for this endpoint.
    End point type
    Secondary
    End point timeframe
    From baseline (week 0) to end of treatment (week 52)
    End point values
    		 Semaglutide Placebo
    Number of subjects analysed
    294
    295
    Units: Ratio of HDL
        geometric mean (geometric coefficient of variation)
    1.04 ( 15.95 )
    0.99 ( 13.91 )
    No statistical analyses for this end point

    Secondary: Change in triglycerides

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    End point title
    		 Change in triglycerides
    End point description
    Change in Triglycerides from baseline to week 52 is presented as ratio to baseline. The endpoint is evaluated based on the on-treatment without rescue treatment observation period. This period includes assessments and events for the time period where participants were exposed to trial product and before rescue treatment (medication or revascularisation procedure). Full Analysis Set (FAS). Overall Number of Participants Analyzed = number of participants with available data for this endpoint.
    End point type
    Secondary
    End point timeframe
    From baseline (week 0) to end of treatment (week 52)
    End point values
    		 Semaglutide Placebo
    Number of subjects analysed
    305
    310
    Units: Ratio of triglycerides
        geometric mean (geometric coefficient of variation)
    0.80 ( 45.95 )
    0.95 ( 41.73 )
    No statistical analyses for this end point

    Secondary: Change in Short Form 36 (SF-36) physical functioning domain

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    End point title
    		 Change in Short Form 36 (SF-36) physical functioning domain
    End point description
    SF-36 is a 36-item patient-reported survey of patient health that measures participant's overall health-related quality of life (HRQoL). SF-36v2 (acute version) questionnaire measured 8 domains of functional health, well-being, 2 component summary scores (physical and mental component summary). 0-100 scale scores from the SF-36 were converted to norm-based scores (Range: 19.03 to 57.60) to enable a direct interpretation in relation to distribution of scores in the 2009 U.S. general population. Positive change score indicates improvement in participant health status. Endpoint is evaluated based on on-treatment without rescue treatment observation period. This period includes assessments, events for time period where participants were exposed to trial product and before rescue treatment (medication or revascularisation procedure). Full Analysis Set (FAS). Overall Number of Participants Analyzed = number of participants with available data for this endpoint.
    End point type
    Secondary
    End point timeframe
    From baseline (week 0) to end of treatment (week 52)
    End point values
    		 Semaglutide Placebo
    Number of subjects analysed
    311
    320
    Units: Scores on a scale
        arithmetic mean (standard deviation)
    2.98 ( 7.32 )
    1.52 ( 7.17 )
    No statistical analyses for this end point

    Secondary: Change in Toe–Brachial Index (TBI)

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    End point title
    		 Change in Toe–Brachial Index (TBI)
    End point description
    Change in TBI from baseline to week 52 is presented. TBI is calculated as a ratio of the toe systolic pressure to the higher systolic pressure measured in both arms. TBI is measured at both left and right leg and the analysis endpoint is defined as the lower of the two indices. A TBI range of above or equal to 0.7 is considered normal, whereas a TBI less than 0.7 is considered abnormal. The endpoint is evaluated based on the on-treatment without rescue treatment observation period. This period includes assessments and events for the time period where participants were exposed to trial product and before rescue treatment (medication or revascularisation procedure). Full Analysis Set (FAS). Overall Number of Participants Analyzed = number of participants with available data for this endpoint.
    End point type
    Secondary
    End point timeframe
    From screening (week -2) to end of treatment (week 52)
    End point values
    		 Semaglutide Placebo
    Number of subjects analysed
    297
    301
    Units: Ratio of TBI
        geometric mean (geometric coefficient of variation)
    1.07 ( 34.4 )
    1.04 ( 37.3 )
    No statistical analyses for this end point

    Secondary: Change in Walking Impairment Questionnaire (WIQ) global score

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    End point title
    		 Change in Walking Impairment Questionnaire (WIQ) global score
    End point description
    WIQ consists of three domains, speed, distance, stair climbing, consisting of in total 14 questions. Each response is weighted based on difficulty of task. Domain scores are determined by dividing weighted answers by maximum possible weighted score, multiplying by 100. Global score is calculated as mean of three domain scores (ranged from 0% to 100%). Global score of 0% represents inabil-ity to perform any of tasks, 100% represents no difficulty with any of tasks. Higher scores indicate better walking ability, less impairment. Endpoint is evaluated based on on-treatment without rescue treatment observation period. This period includes assessments, events for time period where participants were exposed to trial product and before rescue treatment (medication or revascularisation procedure). Full Analysis Set (FAS). Overall Number of Participants Analyzed = number of participants with available data for this endpoint.
    End point type
    Secondary
    End point timeframe
    From baseline (week 0) to end of treatment (week 52)
    End point values
    		 Semaglutide Placebo
    Number of subjects analysed
    312
    321
    Units: %-point scores on a scale
        arithmetic mean (standard deviation)
    9.48 ( 18.63 )
    6.51 ( 20.53 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Until week 57
    Adverse event reporting additional description
    All presented adverse events are treatment emergent adverse events (TEAEs). A Treatment Emergent Adverse Event (TEAE) is defined as an AE with onset in the on-treatment observation period.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    27
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received once-weekly (OW) subcutaneous injection (s. c.) of placebo matched for semaglutide for 52 weeks.

    Reporting group title
    Semaglutide
    Reporting group description
    		 Participants received once-weekly (OW) subcutaneous injection (s. c.) of semaglutide for 52 weeks. Participants received a dose of 0.25 milligrams (mg) from week 0 to week 4, then the dose was increased to 0.5 mg from week 4 to week 8. From week 8 to week 52, the dosage was 1.0 mg.

    Serious adverse events
    		 Placebo Semaglutide
    Total subjects affected by serious adverse events
         subjects affected / exposed
    78 / 395 (19.75%)
    74 / 396 (18.69%)
         number of deaths (all causes)
    9
    4
         number of deaths resulting from adverse events
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma of colon
         subjects affected / exposed
    1 / 395 (0.25%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Bladder cancer stage 0, with cancer in situ
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchial carcinoma
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder cancer
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clear cell renal cell carcinoma
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colorectal cancer metastatic
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric cancer
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Invasive ductal breast carcinoma
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung adenocarcinoma stage II
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal carcinoma
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung adenocarcinoma stage I
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastatic malignant melanoma
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung cancer metastatic
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung adenocarcinoma
         subjects affected / exposed
    1 / 395 (0.25%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pancreatic carcinoma metastatic
         subjects affected / exposed
    2 / 395 (0.51%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pancreatic carcinoma
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Plasma cell myeloma
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal cancer
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small cell lung cancer
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Accelerated hypertension
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriosclerosis
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive urgency
         subjects affected / exposed
    0 / 395 (0.00%)
    2 / 396 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intermittent claudication
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery stenosis
         subjects affected / exposed
    2 / 395 (0.51%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery occlusion
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    5 / 395 (1.27%)
    4 / 396 (1.01%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Orthostatic hypotension
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    3 / 395 (0.76%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Death
         subjects affected / exposed
    2 / 395 (0.51%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sudden cardiac death
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Tissue discolouration
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Scrotal ulcer
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asthma
         subjects affected / exposed
    0 / 395 (0.00%)
    2 / 396 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Epistaxis
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemothorax
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory arrest
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 395 (0.00%)
    2 / 396 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Neutrophil count decreased
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Ankle fracture
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain contusion
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carotid artery restenosis
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Concussion
         subjects affected / exposed
    2 / 395 (0.51%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fracture displacement
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    0 / 395 (0.00%)
    2 / 396 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Limb injury
         subjects affected / exposed
    1 / 395 (0.25%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haematuria
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal fracture
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tendon rupture
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Hydrocele
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    5 / 395 (1.27%)
    3 / 396 (0.76%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute coronary syndrome
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Angina unstable
         subjects affected / exposed
    2 / 395 (0.51%)
    3 / 396 (0.76%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    2 / 395 (0.51%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    1 / 395 (0.25%)
    2 / 396 (0.51%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure acute
         subjects affected / exposed
    1 / 395 (0.25%)
    2 / 396 (0.51%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure chronic
         subjects affected / exposed
    0 / 395 (0.00%)
    2 / 396 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cardiogenic shock
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    0 / 395 (0.00%)
    4 / 396 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery occlusion
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery stenosis
         subjects affected / exposed
    0 / 395 (0.00%)
    3 / 396 (0.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic cardiomyopathy
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericarditis
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    1 / 395 (0.25%)
    2 / 396 (0.51%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus node dysfunction
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Carotid artery stenosis
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    3 / 395 (0.76%)
    3 / 396 (0.76%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic neuropathy
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Facial paresis
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    IIIrd nerve paralysis
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    1 / 395 (0.25%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lacunar stroke
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Polyneuropathy
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    1 / 395 (0.25%)
    2 / 396 (0.51%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    0 / 395 (0.00%)
    2 / 396 (0.51%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 395 (0.25%)
    2 / 396 (0.51%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo positional
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Cataract
         subjects affected / exposed
    2 / 395 (0.51%)
    2 / 396 (0.51%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Optic nerve disorder
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal symptom
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic gastritis
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenitis
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric ulcer
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    1 / 395 (0.25%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 395 (0.25%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus paralytic
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal ischaemia
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophagitis
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic pseudocyst
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophagitis haemorrhagic
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stomach mass
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis acute
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic hepatitis
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Diabetic foot
         subjects affected / exposed
    2 / 395 (0.51%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin ulcer
         subjects affected / exposed
    1 / 395 (0.25%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 395 (0.00%)
    3 / 396 (0.76%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar spinal stenosis
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pathological fracture
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal osteoarthritis
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal stenosis
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Abdominal abscess
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abscess limb
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anal abscess
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    2 / 395 (0.51%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain abscess
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    2 / 395 (0.51%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    2 / 395 (0.51%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cystitis
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    1 / 395 (0.25%)
    3 / 396 (0.76%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver abscess
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia viral
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    5 / 395 (1.27%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rotavirus infection
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal abscess
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 395 (0.25%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic endocarditis
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 395 (0.25%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Wound infection
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Alkalosis
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic ketoacidosis
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    0 / 395 (0.00%)
    1 / 396 (0.25%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Obesity
         subjects affected / exposed
    1 / 395 (0.25%)
    0 / 396 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo Semaglutide
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    24 / 395 (6.08%)
    47 / 396 (11.87%)
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    3 / 395 (0.76%)
    22 / 396 (5.56%)
         occurrences all number
    4
    26
    Infections and infestations
    COVID-19
         subjects affected / exposed
    21 / 395 (5.32%)
    30 / 396 (7.58%)
         occurrences all number
    21
    32

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    18 Nov 2020
    Due to the Coronavirus disease (COVID-19) pandemic the exclusion and discontinuation criteria were amended to allow for simultaneous participation in trials with the primary objective of evaluating an approved or non-approved investigational medicinal product for prevention or treatment of COVID-19 disease or COVID-19 postinfectious conditions. Additional blood sampling was included for PK assessment. Plasma semaglutide concentrations was used to describe the exposure-response analysis and other updates.
    18 Apr 2023
    To strengthen approach of submitting a single trial to have the lower extremity peripheral artery disease (PAD) information accepted into the label. This was achieved by elevating the supportive endpoint “Follow-up change in maximum walking distance on a constant load treadmill test” to confirmatory secondary endpoint with the purpose of ensuring that the follow-up period results are taken into consideration by regulators. Additionally, this amendment includes the inversion of confirmatory endpoints “Change in pain free walking distance on a constant load treadmill test” and “Change in VascuQoL-6 score”, as well as a small change in the wording of the secondary objective related to VascuQoL-6 questionnaire, to clarify the measured concepts and other updates.

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

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