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 were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   44335   clinical trials with a EudraCT protocol, of which   7366   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).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    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:
    A 52 week study comparing the efficacy and safety of once weekly IcoSema and once weekly semaglutide, both treatment arms with or without oral anti diabetic drugs, in participants with type 2 diabetes inadequately controlled with a GLP 1 receptor agonist. COMBINE 2

    Summary
    EudraCT number
    		 2020-005308-21
    Trial protocol
    		 SK   GR   SE   HU  
    Global end of trial date
    16 Jan 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    01 Feb 2025
    First version publication date
    01 Feb 2025
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    NN1535-4592
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT05259033
    WHO universal trial number (UTN)
    		 U1111-1260-8268
    Other trial identifiers
    		 jRCT2051220044: Japanese trial registration number, CTR20220767: China Drug Trials (China)
    Sponsors
    Sponsor organisation name
    Novo Nordisk A/S
    Sponsor organisation address
    Novo Allé, 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
    01 Mar 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    16 Jan 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To confirm superiority of once weekly IcoSema compared with once weekly semaglutide, both treatment arms with or without OADs, in terms of glycaemic control measured by change in HbA1c from baseline after 52 weeks in participants with T2D inadequately controlled with a GLP 1 receptor agonist.
    Protection of trial subjects
    The study was conducted in accordance with the Declaration of Helsinki (64th World Medical Association [WMA] General Assembly, Fortaleza, Brazil. Oct 2013) and International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice, including archiving of essential documents.
    Background therapy
    		 Not applicable
    Evidence for comparator
    		 Not applicable
    Actual start date of recruitment
    11 Apr 2022
    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
    Brazil: 63
    Country: Number of subjects enrolled
    Canada: 35
    Country: Number of subjects enrolled
    Switzerland: 13
    Country: Number of subjects enrolled
    China: 50
    Country: Number of subjects enrolled
    France: 35
    Country: Number of subjects enrolled
    Greece: 72
    Country: Number of subjects enrolled
    Hungary: 34
    Country: Number of subjects enrolled
    Israel: 35
    Country: Number of subjects enrolled
    Japan: 100
    Country: Number of subjects enrolled
    Slovakia: 46
    Country: Number of subjects enrolled
    Sweden: 9
    Country: Number of subjects enrolled
    Taiwan: 20
    Country: Number of subjects enrolled
    United States: 171
    Worldwide total number of subjects
    683
    EEA total number of subjects
    196
    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)
    455
    From 65 to 84 years
    228
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Trial was conducted at 124 sites in 13 countries as follows (number of sites that screened subjects/number of sites that randomised subjects):Brazil (6/6); Canada (10/9); China Mainland (11/11); France (5/5); Greece (8/8); Hungary (4/4); Israel (6/6); Japan (9/9); Slovakia (6/6); Sweden (3/3); Switzerland (3/3); Taiwan (5/5);United States (48/46).

    Pre-assignment
    Screening details
    		 Subjects were randomised in 1:1 ratio to receive subcutaneous (s.c.) injection of either IcoSema or semaglutide once weekly. The trial had a 52-week treatment period followed by a 5-week follow-up period.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 IcoSema
    Arm description
    		 Subjects received once weekly 700 units per millilitre (U/mL) of insulin icodec and 2 milligram per millilitre (mg/mL) of semaglutide subcutaneously for 52 weeks. Participants were to perform once daily pre-breakfast self-monitoring plasma glucose (SMPG). The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: dose re-duced by 10 U; 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: dose increased by 10 U. Dose titration of IcoSema was based on the respective premeal(s) and bedtime self-measured plasma glucose (SMPG) measured weekly.
    Arm type
    		 Experimental

    Investigational medicinal product name
    IcoSema
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received icodec once weekly subcutaneously.

    Arm title
    		 Semaglutide
    Arm description
    		 Subjects received once weekly semaglutide subcutaneously in a dose escalation manner, with dose increases every 4 weeks for up to week 8 (0.25 milligrams [mg], 0.5 mg) followed by 1.0 mg once weekly up to the end of treatment period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Semaglutide
    Investigational medicinal product code
    Other name
    Ozempic
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received semaglutide once weekly subcutaneously.

    Number of subjects in period 1
    		IcoSema Semaglutide
    Started
    342
    341
    Full analysis set (FAS)
    342
    341
    Safety analysis set (SAS)
    341
    340
    Exposed
    341
    340
    Completed
    329
    336
    Not completed
    13
    5
         Consent withdrawn by subject
    10
    5
         Death
    2
    -
         Lost to follow-up
    1
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    IcoSema
    Reporting group description
    		 Subjects received once weekly 700 units per millilitre (U/mL) of insulin icodec and 2 milligram per millilitre (mg/mL) of semaglutide subcutaneously for 52 weeks. Participants were to perform once daily pre-breakfast self-monitoring plasma glucose (SMPG). The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: dose re-duced by 10 U; 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: dose increased by 10 U. Dose titration of IcoSema was based on the respective premeal(s) and bedtime self-measured plasma glucose (SMPG) measured weekly.

    Reporting group title
    Semaglutide
    Reporting group description
    		 Subjects received once weekly semaglutide subcutaneously in a dose escalation manner, with dose increases every 4 weeks for up to week 8 (0.25 milligrams [mg], 0.5 mg) followed by 1.0 mg once weekly up to the end of treatment period.

    Reporting group values
    		 IcoSema Semaglutide Total
    Number of subjects
    		 342 341 683
    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)
    		 213 242 455
        From 65-84 years
    		 129 99 228
        85 years and over
    		 0 0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 59.9 ( 10.5 ) 58.3 ( 9.8 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 141 145 286
        Male
    		 201 196 397

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    IcoSema
    Reporting group description
    		 Subjects received once weekly 700 units per millilitre (U/mL) of insulin icodec and 2 milligram per millilitre (mg/mL) of semaglutide subcutaneously for 52 weeks. Participants were to perform once daily pre-breakfast self-monitoring plasma glucose (SMPG). The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: dose re-duced by 10 U; 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: dose increased by 10 U. Dose titration of IcoSema was based on the respective premeal(s) and bedtime self-measured plasma glucose (SMPG) measured weekly.

    Reporting group title
    Semaglutide
    Reporting group description
    		 Subjects received once weekly semaglutide subcutaneously in a dose escalation manner, with dose increases every 4 weeks for up to week 8 (0.25 milligrams [mg], 0.5 mg) followed by 1.0 mg once weekly up to the end of treatment period.

    Primary: Change in glycosylated haemoglobin (HbA1c)

    		 Close Top of page
    End point title
    		 Change in glycosylated haemoglobin (HbA1c)
    End point description
    Change from baseline (week 0) to week 52 in HbA1c is presented.The outcome measure was evaluated based on the data from in study period, where all data from randomisation until last date of any of the following: 1) last direct subjects-site contact; 2) subjects who withdrew their informed consent; 3) last subjects-investigator contact as defined by the investigator for subjects who lost to follow-up (i.e. possibly an unscheduled phone visit); 4) death of subjects who died before any of the above. Full Analysis Set (FAS) which comprised all randomised subjects. Number of subjects analyzed = subjects with available data for this outcome measure.
    End point type
    Primary
    End point timeframe
    From baseline week 0 (V2) to week 52 (V54)
    End point values
    		 IcoSema Semaglutide
    Number of subjects analysed
    325
    335
    Units: Percentage point of HbA1c
        arithmetic mean (standard deviation)
    -1.40 ( 0.91 )
    -0.86 ( 0.96 )
    Statistical analysis title
    		 IcoSema - Semaglutide
    Statistical analysis description
    Hypothetical estimand
    Comparison groups
    IcoSema v Semaglutide
    Number of subjects included in analysis
    660
    Analysis specification
    Pre-specified
    Analysis type
    		 [1]
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 Estimated treatment difference
    Point estimate
    -0.44
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.56
         upper limit
    		 -0.33
    Notes
    [1] - Responses were analysed using an analysis of covariance (ANCOVA) model with region and randomised treatment as fixed factors and baseline HbA1c as covariate. Each imputed dataset is analysed separately and estimates are combined using Rubin's rules.

    Secondary: Change in fasting plasma glucose (FPG)

    		 Close Top of page
    End point title
    		 Change in fasting plasma glucose (FPG)
    End point description
    Change from baseline (week 0) to week 52 in FPG is presented.The outcome measure was evaluated based on the data from in study period, where all data from randomisation until last date of any of the following: 1) last direct subjects-site contact; 2) subjects who withdrew their informed consent; 3) last subjects-investigator contact as defined by the investigator for subjects who lost to follow-up (i.e. possibly an unscheduled phone visit); 4) death of subjects who died before any of the above. FAS which comprised all randomised subjects. Number of subjects analyzed = subjects with available data for this outcome measure.
    End point type
    Secondary
    End point timeframe
    From baseline week 0 (V2) to week 52 (V54)
    End point values
    		 IcoSema Semaglutide
    Number of subjects analysed
    313
    317
    Units: Millimoles per litre (mmol/L)
        arithmetic mean (standard deviation)
    -2.74 ( 2.85 )
    -1.41 ( 2.89 )
    No statistical analyses for this end point

    Secondary: Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL), confirmed by BG meter)

    		 Close Top of page
    End point title
    		 Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL), confirmed by BG meter)
    End point description
    Hypoglycaemic episodes were classified according to the American Diabetes Association/ International Hypoglycaemia Study Group, where glycemic criteria for level 2 was < 3.0 mmol/L (54 mg/dL). The outcome measure was evaluated based on data from on treatment period, where all data from date of first dose of randomised treatment as recorded on the electronic case report form (eCRF) until the first date of any of the following: 1)last follow-up visit (V56); 2) last date on randomised treatment +6 weeks (corresponding to 5 weeks after the end of the dosing interval for both treatment arms); 3) end-date for the in-study data points sets. SAS included all subjects exposed to randomised treatment.
    End point type
    Secondary
    End point timeframe
    From baseline week 0 (V2) to week 57 (V56)
    End point values
    		 IcoSema Semaglutide
    Number of subjects analysed
    341
    340
    Units: Episodes
        number (not applicable)
    15
    13
    No statistical analyses for this end point

    Secondary: Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L [54 mg/dL], confirmed by blood glucose [BG] meter) or severe hypoglycaemic episodes (level 3)

    		 Close Top of page
    End point title
    		 Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L [54 mg/dL], confirmed by blood glucose [BG] meter) or severe hypoglycaemic episodes (level 3)
    End point description
    Hypoglycaemic episodes were classified according to the American Diabetes Association/ International Hypoglycaemia Study Group, where glycemic criteria for level 2 was less than (<) 3.0 mmol/L (54 milligram per decilitre [mg/dL]) and level 3 had no specific glucose threshold. The outcome measure was evaluated based on data from on treatment period, where all data from date of first dose of randomised treatment as recorded on the electronic case report form (eCRF) until the first date of any of the following: 1)last follow-up visit (V56); 2) last date on randomised treatment +6 weeks (corresponding to 5 weeks after the end of the dosing interval for both treatment arms); 3) end-date for the in-study data points sets. Safety Analysis Set (SAS) included all subjects exposed to randomised treatment.
    End point type
    Secondary
    End point timeframe
    From baseline week 0 (V2) to week 57 (V56)
    End point values
    		 IcoSema Semaglutide
    Number of subjects analysed
    341
    340
    Units: Episodes
        number (not applicable)
    15
    13
    No statistical analyses for this end point

    Secondary: Number of severe hypoglycaemic episodes (level 3)

    		 Close Top of page
    End point title
    		 Number of severe hypoglycaemic episodes (level 3)
    End point description
    Hypoglycaemic episodes were classified according to the American Diabetes Association/ International Hypoglycaemia Study Group, where glycemic criteria for level 3 had no specific glucose threshold.The outcome measure was evaluated based on data from on treatment period, where all data from date of first dose of randomised treatment as recorded on the electronic case report form (eCRF) until the first date of any of the following: 1)last follow-up visit (V56); 2) last date on randomised treatment +6 weeks (corresponding to 5 weeks after the end of the dosing interval for both treatment arms); 3) end-date for the in-study data points sets. SAS included all subjects exposed to randomised treatment.
    End point type
    Secondary
    End point timeframe
    From baseline week 0 (V2) to week 57 (V56)
    End point values
    		 IcoSema Semaglutide
    Number of subjects analysed
    341
    340
    Units: Episodes
        number (not applicable)
    0
    0
    No statistical analyses for this end point

    Secondary: Change in body weight

    		 Close Top of page
    End point title
    		 Change in body weight
    End point description
    Change from baseline (week 0) to week 52 in body weight is presented. The outcome measure was evaluated based on the data from in study period, where all data from randomisation until last date of any of the following: 1) last direct subjects-site contact; 2) subjects who withdrew their informed consent; 3) last subjects-investigator contact as defined by the investigator for subjects who lost to follow-up (i.e. possibly an unscheduled phone visit); 4) death of subjects who died before any of the above. FAS which comprised all randomised subjects. Number of subjects analyzed = subjects with available data for this outcome measure.
    End point type
    Secondary
    End point timeframe
    From baseline week 0 (V2) to week 52 (V54)
    End point values
    		 IcoSema Semaglutide
    Number of subjects analysed
    325
    336
    Units: Kilogram (kg)
        arithmetic mean (standard deviation)
    0.89 ( 4.36 )
    -3.77 ( 4.60 )
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Week 0 to week 57.
    Adverse event reporting additional description
    Presented AEs are TEAEs, defined as event with onset during on treatment period. Results are based on SAS including all subjects exposed to randomised treatment.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22
    Reporting groups
    Reporting group title
    Semaglutide
    Reporting group description
    		 Subjects received once weekly semaglutide subcutaneously in a dose escalation manner, with dose increases every 4 weeks for up to week 8 (0.25 milligrams [mg], 0.5 mg) followed by 1.0 mg once weekly up to the end of treatment period.

    Reporting group title
    IcoSema
    Reporting group description
    		 Subjects received once weekly 700 units per millilitre (U/mL) of insulin icodec and 2 milligram per millilitre (mg/mL) of semaglutide subcutaneously for 52 weeks. Participants were to perform once daily pre-breakfast self-monitoring plasma glucose (SMPG). The dose was adjusted based on 3 pre-breakfast SMPG values measured on the 2 previous days and the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 mmol/L: dose re-duced by 10 U; 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: dose increased by 10 U. Dose titration of IcoSema was based on the respective premeal(s) and bedtime self-measured plasma glucose (SMPG) measured weekly.

    Serious adverse events
    		 Semaglutide IcoSema
    Total subjects affected by serious adverse events
         subjects affected / exposed
    21 / 340 (6.18%)
    38 / 341 (11.14%)
         number of deaths (all causes)
    0
    2
         number of deaths resulting from adverse events
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acoustic neuroma
         subjects affected / exposed
    1 / 340 (0.29%)
    0 / 341 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Adenocarcinoma of colon
         subjects affected / exposed
    0 / 340 (0.00%)
    1 / 341 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colorectal adenoma
         subjects affected / exposed
    1 / 340 (0.29%)
    0 / 341 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma of the tongue
         subjects affected / exposed
    0 / 340 (0.00%)
    1 / 341 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma of head and neck
         subjects affected / exposed
    1 / 340 (0.29%)
    0 / 341 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ovarian adenoma
         subjects affected / exposed
    0 / 340 (0.00%)
    1 / 341 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 340 (0.00%)
    1 / 341 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    0 / 340 (0.00%)
    1 / 341 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypovolaemic shock
         subjects affected / exposed
    1 / 340 (0.29%)
    0 / 341 (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
    0 / 340 (0.00%)
    1 / 341 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Cardioversion
         subjects affected / exposed
    0 / 340 (0.00%)
    1 / 341 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    0 / 340 (0.00%)
    1 / 341 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sudden death
         subjects affected / exposed
    0 / 340 (0.00%)
    1 / 341 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Reproductive system and breast disorders
    Prostatitis
         subjects affected / exposed
    0 / 340 (0.00%)
    1 / 341 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 340 (0.00%)
    1 / 341 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 340 (0.29%)
    0 / 341 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    1 / 340 (0.29%)
    0 / 341 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Femoral neck fracture
         subjects affected / exposed
    1 / 340 (0.29%)
    3 / 341 (0.88%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    0 / 340 (0.00%)
    1 / 341 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meniscus injury
         subjects affected / exposed
    0 / 340 (0.00%)
    1 / 341 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    0 / 340 (0.00%)
    1 / 341 (0.29%)
         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
    1 / 340 (0.29%)
    0 / 341 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Patella fracture
         subjects affected / exposed
    0 / 340 (0.00%)
    1 / 341 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal column injury
         subjects affected / exposed
    1 / 340 (0.29%)
    0 / 341 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ulna fracture
         subjects affected / exposed
    0 / 340 (0.00%)
    1 / 341 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Angina unstable
         subjects affected / exposed
    0 / 340 (0.00%)
    1 / 341 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    1 / 340 (0.29%)
    0 / 341 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    0 / 340 (0.00%)
    2 / 341 (0.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    1 / 340 (0.29%)
    0 / 341 (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
    1 / 340 (0.29%)
    0 / 341 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure chronic
         subjects affected / exposed
    0 / 340 (0.00%)
    1 / 341 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Arteriosclerosis coronary artery
         subjects affected / exposed
    0 / 340 (0.00%)
    1 / 341 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Left ventricular failure
         subjects affected / exposed
    1 / 340 (0.29%)
    0 / 341 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 340 (0.00%)
    1 / 341 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular extrasystoles
         subjects affected / exposed
    0 / 340 (0.00%)
    1 / 341 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    1 / 340 (0.29%)
    0 / 341 (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 / 340 (0.00%)
    2 / 341 (0.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cerebral infarction
         subjects affected / exposed
    0 / 340 (0.00%)
    1 / 341 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    0 / 340 (0.00%)
    1 / 341 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Migraine without aura
         subjects affected / exposed
    0 / 340 (0.00%)
    1 / 341 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    VIth nerve paralysis
         subjects affected / exposed
    1 / 340 (0.29%)
    0 / 341 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Cataract
         subjects affected / exposed
    1 / 340 (0.29%)
    0 / 341 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Optic ischaemic neuropathy
         subjects affected / exposed
    1 / 340 (0.29%)
    0 / 341 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Colon dysplasia
         subjects affected / exposed
    1 / 340 (0.29%)
    0 / 341 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 340 (0.29%)
    0 / 341 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Food poisoning
         subjects affected / exposed
    0 / 340 (0.00%)
    1 / 341 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 340 (0.29%)
    0 / 341 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 340 (0.29%)
    0 / 341 (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
    0 / 340 (0.00%)
    1 / 341 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 340 (0.29%)
    1 / 341 (0.29%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis acute
         subjects affected / exposed
    1 / 340 (0.29%)
    2 / 341 (0.59%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 340 (0.29%)
    1 / 341 (0.29%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    0 / 340 (0.00%)
    1 / 341 (0.29%)
         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
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 340 (0.00%)
    2 / 341 (0.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lumbar spinal stenosis
         subjects affected / exposed
    2 / 340 (0.59%)
    0 / 341 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    1 / 340 (0.29%)
    0 / 341 (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 sepsis
         subjects affected / exposed
    0 / 340 (0.00%)
    1 / 341 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    0 / 340 (0.00%)
    1 / 341 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    1 / 340 (0.29%)
    0 / 341 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Otitis media
         subjects affected / exposed
    0 / 340 (0.00%)
    1 / 341 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Otitis media chronic
         subjects affected / exposed
    0 / 340 (0.00%)
    1 / 341 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 340 (0.29%)
    2 / 341 (0.59%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 340 (0.29%)
    0 / 341 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic ketoacidosis
         subjects affected / exposed
    0 / 340 (0.00%)
    1 / 341 (0.29%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ketoacidosis
         subjects affected / exposed
    1 / 340 (0.29%)
    0 / 341 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lactic acidosis
         subjects affected / exposed
    1 / 340 (0.29%)
    0 / 341 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Type 2 diabetes mellitus
         subjects affected / exposed
    1 / 340 (0.29%)
    0 / 341 (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
    		 Semaglutide IcoSema
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    159 / 340 (46.76%)
    163 / 341 (47.80%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    6 / 340 (1.76%)
    20 / 341 (5.87%)
         occurrences all number
    6
    25
    Eye disorders
    Diabetic retinopathy
         subjects affected / exposed
    10 / 340 (2.94%)
    19 / 341 (5.57%)
         occurrences all number
    10
    20
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    17 / 340 (5.00%)
    11 / 341 (3.23%)
         occurrences all number
    22
    14
    Diarrhoea
         subjects affected / exposed
    41 / 340 (12.06%)
    38 / 341 (11.14%)
         occurrences all number
    82
    53
    Vomiting
         subjects affected / exposed
    22 / 340 (6.47%)
    17 / 341 (4.99%)
         occurrences all number
    48
    24
    Nausea
         subjects affected / exposed
    39 / 340 (11.47%)
    40 / 341 (11.73%)
         occurrences all number
    73
    65
    Infections and infestations
    COVID-19
         subjects affected / exposed
    49 / 340 (14.41%)
    51 / 341 (14.96%)
         occurrences all number
    53
    52
    Nasopharyngitis
         subjects affected / exposed
    33 / 340 (9.71%)
    33 / 341 (9.68%)
         occurrences all number
    45
    45
    Upper respiratory tract infection
         subjects affected / exposed
    29 / 340 (8.53%)
    22 / 341 (6.45%)
         occurrences all number
    34
    34

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

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

    European Medicines Agency © 1995-Sat May 10 00:48:33 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA