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    Clinical Trial Results:
    A 78-week trial comparing the effect and safety of once weekly insulin icodec and once daily insulin glargine 100 units/mL, both in combination with non-insulin anti-diabetic treatment, in insulin naïve subjects with type 2 diabetes

    Summary
    EudraCT number
    		 2020-000442-34
    Trial protocol
    		 GB   SK   PL   HR   IT  
    Global end of trial date
    01 Dec 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    16 Dec 2023
    First version publication date
    16 Dec 2023
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    NN1436-4477
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04460885
    WHO universal trial number (UTN)
    		 U1111-1247-3878
    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
    21 Dec 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    01 Dec 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To demonstrate the effect on glycaemic control of once weekly insulin icodec, in combination with non-insulin anti-diabetic drugs, in insulin naive subjects with type 2 diabetes (T2D). This included comparing the difference in change from baseline in glycosylated haemoglobin (HbA1c) between insulin icodec and insulin glargine after 52 weeks of treatment to a non-inferiority limit of 0.3%.
    Protection of trial subjects
    The trial was conducted in accordance with the Declaration of Helsinki (64th World Medical Association [WMA] general Assembly; Oct 2013) and International Conference on Harmonization (ICH) Good Clinical Practice, including archiving of essential documents, (Current Step 4 version, Nov 2016) and 21 Code of Federal Regulations (CFR) 312.120
    Background therapy
    		 Not applicable
    Evidence for comparator
    		 Not applicable
    Actual start date of recruitment
    25 Nov 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
    Spain: 36
    Country: Number of subjects enrolled
    United Kingdom: 48
    Country: Number of subjects enrolled
    Croatia: 36
    Country: Number of subjects enrolled
    India: 88
    Country: Number of subjects enrolled
    Israel: 37
    Country: Number of subjects enrolled
    Italy: 46
    Country: Number of subjects enrolled
    Japan: 164
    Country: Number of subjects enrolled
    Mexico: 41
    Country: Number of subjects enrolled
    Poland: 88
    Country: Number of subjects enrolled
    Russian Federation: 117
    Country: Number of subjects enrolled
    Slovakia: 63
    Country: Number of subjects enrolled
    United States: 220
    Worldwide total number of subjects
    984
    EEA total number of subjects
    269
    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)
    665
    From 65 to 84 years
    319
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 The trial was conducted in 12 countries. The total number of sites which screened subjects/total number of sites which randomised subjects is as follows: Croatia (4/4), India (9/9), Israel (5/5), Italy (5/5), Japan (14/14), Mexico (3/3), Poland (8/8), Russia (14/14), Slovakia (7/7), Spain (5/5), United Kingdom (11/11) and United States (56/52).

    Pre-assignment
    Screening details
    		 A total of 984 subjects were randomised and exposed to the trial product in 1:1 ratio and 949 subjects completed the trial.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Insulin icodec
    Arm description
    		 Subjects received once-weekly subcutaneous injection of insulin icodec at a starting dose of 70 U for 52 weeks using PDS 290 pre-filled injector in combination with non-insulin anti-diabetic drugs. The dose adjustment was based on the three pre-breakfast self-monitored plasma glucose (SMPG) values measured on two days prior to titration and on the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 millimoles per liter (mmol/L): dose reduced by 20 units (U); 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: dose increased by 20 units.
    Arm type
    		 Experimental

    Investigational medicinal product name
    insulin icodec 700 U/mL PDS290
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Insulin icodec was administered once weekly subcutaneously into the thigh, upper arm or abdomen using the PDS290 pen injector.

    Arm title
    		 Insulin glargine
    Arm description
    		 Subjects received once daily subcutaneous injection of insulin glargine at a starting dose of 10 U using SoloSTAR pre-filled pen injector in combination with non-insulin anti-diabetic drugs. The dose adjustment was based on the three pre-breakfast self-monitored plasma glucose (SMPG) values measured on two days prior to titration and on the day of the contact. If atleast one pre-breakfast SMPG value was: < 4.4 mmol/L: the dose was reduced by 3 U; 4.4-7.2: no dose adjustment required and >7.2 mmol/L: dose was increased by 3 U
    Arm type
    		 Experimental

    Investigational medicinal product name
    Lantus
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Insulin glargine was administered once daily subcutaneously into the thigh, upper arm or abdomen using the 3 mL SoloSTAR pre-filled pen injector.

    Number of subjects in period 1
    		Insulin icodec Insulin glargine
    Started
    492
    492
    Completed
    474
    475
    Not completed
    18
    17
         Physician decision
    2
    1
         Consent withdrawn by subject
    6
    8
         Death
    5
    4
         Lost to follow-up
    4
    4
         Site closure
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Insulin icodec
    Reporting group description
    		 Subjects received once-weekly subcutaneous injection of insulin icodec at a starting dose of 70 U for 52 weeks using PDS 290 pre-filled injector in combination with non-insulin anti-diabetic drugs. The dose adjustment was based on the three pre-breakfast self-monitored plasma glucose (SMPG) values measured on two days prior to titration and on the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 millimoles per liter (mmol/L): dose reduced by 20 units (U); 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: dose increased by 20 units.

    Reporting group title
    Insulin glargine
    Reporting group description
    		 Subjects received once daily subcutaneous injection of insulin glargine at a starting dose of 10 U using SoloSTAR pre-filled pen injector in combination with non-insulin anti-diabetic drugs. The dose adjustment was based on the three pre-breakfast self-monitored plasma glucose (SMPG) values measured on two days prior to titration and on the day of the contact. If atleast one pre-breakfast SMPG value was: < 4.4 mmol/L: the dose was reduced by 3 U; 4.4-7.2: no dose adjustment required and >7.2 mmol/L: dose was increased by 3 U

    Reporting group values
    		 Insulin icodec Insulin glargine Total
    Number of subjects
    		 492 492 984
    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)
    		 333 332 665
        From 65-84 years
    		 159 160 319
        85 years and over
    		 0 0 0
    Age Continuous
    Units: years
        median (full range (min-max))
    		 60.00 (27.00 to 84.00) 60.00 (28.00 to 80.00) -
    Gender Categorical
    Units: Subjects
        Female
    		 197 229 426
        Male
    		 295 263 558

    End points

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    End points reporting groups
    Reporting group title
    Insulin icodec
    Reporting group description
    		 Subjects received once-weekly subcutaneous injection of insulin icodec at a starting dose of 70 U for 52 weeks using PDS 290 pre-filled injector in combination with non-insulin anti-diabetic drugs. The dose adjustment was based on the three pre-breakfast self-monitored plasma glucose (SMPG) values measured on two days prior to titration and on the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 millimoles per liter (mmol/L): dose reduced by 20 units (U); 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: dose increased by 20 units.

    Reporting group title
    Insulin glargine
    Reporting group description
    		 Subjects received once daily subcutaneous injection of insulin glargine at a starting dose of 10 U using SoloSTAR pre-filled pen injector in combination with non-insulin anti-diabetic drugs. The dose adjustment was based on the three pre-breakfast self-monitored plasma glucose (SMPG) values measured on two days prior to titration and on the day of the contact. If atleast one pre-breakfast SMPG value was: < 4.4 mmol/L: the dose was reduced by 3 U; 4.4-7.2: no dose adjustment required and >7.2 mmol/L: dose was increased by 3 U

    Primary: Change in glycated haemoglobin (HbA1c)

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    End point title
    		 Change in glycated haemoglobin (HbA1c)
    End point description
    Change in HbA1c from baseline week 0 (V2) to week 52 (V46) was presented. The endpoint data was evaluated based on the in-trial observation period. The in-trial period started at randomization and ended at the date of: The last direct subject-site contact, withdrawal for subjects who withdrew their informed consent, the last subject-investigator contact as defined by the investigator for subjects who were lost to follow-up (i.e., possibly an unscheduled phone visit), death for subjects who died before any of the above. Full analysis set included all randomized subjects.
    End point type
    Primary
    End point timeframe
    From baseline week 0 (V2) to week 52 (V46)
    End point values
    		 Insulin icodec Insulin glargine
    Number of subjects analysed
    492
    492
    Units: Percentage (%) of HbA1c
        least squares mean (standard error)
    -1.55 ± 0.06
    -1.35 ± 0.05
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The response and change from baseline in response after 52 weeks are analysed using an analysis of covariance (ANCOVA) model with treatment and region as fixed factors, and baseline response as covariate.
    Comparison groups
    Insulin icodec v Insulin glargine
    Number of subjects included in analysis
    984
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 Treatment difference
    Point estimate
    -0.19
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.36
         upper limit
    		 -0.03

    Secondary: Change in fasting plasma glucose (FPG)

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    End point title
    		 Change in fasting plasma glucose (FPG)
    End point description
    Change in FPG from baseline (week 0) to week 52 is presented. The outcome data was evaluated based on the in-trial observation period. The in-trial period started at randomization and ended at the date of: The last direct subject-site contact, withdrawal for subjects who withdrew their informed consent, the last subject-investigator contact as defined by the investigator for subjects who were lost to follow-up (i.e., possibly an unscheduled phone visit), death for subjects who died before any of the above. Full analysis set included all randomized subjects. Number of subjects analysed = Subjects with available data for the endpoint.
    End point type
    Secondary
    End point timeframe
    From baseline week 0 (V2) to week 52 (V46)
    End point values
    		 Insulin icodec Insulin glargine
    Number of subjects analysed
    480
    474
    Units: millimoles per liter (mmol/L)
        least squares mean (standard error)
    -3.35 ± 0.09
    -3.33 ± 0.09
    No statistical analyses for this end point

    Secondary: Time in target range 3.9-10.0 mmol/L (70-180 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6

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    End point title
    		 Time in target range 3.9-10.0 mmol/L (70-180 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6
    End point description
    Time in target range 3.9-10.0 millimoles per liter (mmol/L) (70-180 milligrams per deciliter [mg/dL]) using continuous glucose monitoring (CGM) system, Dexcom G6 is presented. Time in target range is defined as 100 times the number of recorded measurements in glycaemic target range 3.9-10.0 mmol/L (70-180 mg/dL), both inclusive, divided by the total number of recorded measurements. The in-trial period started at randomization and ended at the date of: The last direct subject-site contact, withdrawal for subjects who withdrew their informed consent, the last subject-investigator contact as defined by the investigator for subjects who were lost to follow-up (i.e., possibly an unscheduled phone visit), death for subjects who died before any of the above. Full analysis set included all randomized subjects. Number of subjects analysed=Subjects with available data for the endpoint.
    End point type
    Secondary
    End point timeframe
    From week 48 (V42) to week 52 (V46)
    End point values
    		 Insulin icodec Insulin glargine
    Number of subjects analysed
    439
    440
    Units: Percentage of time
        arithmetic mean (standard deviation)
    71.94 ± 18.23
    66.90 ± 18.19
    No statistical analyses for this end point

    Secondary: Number of severe hypoglycaemic episodes (level 3)

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    End point title
    		 Number of severe hypoglycaemic episodes (level 3)
    End point description
    Number of severe hypoglycaemic episodes (level 3) is presented. Severe hypoglycaemic episode is defined as hypoglycaemia with severe cognitive impairment requiring external assistance for recovery. The outcome data was evaluated based on main-on-treatment period. Main-on-treatment period started with onset date on or after the first dose of trial product and no later than the first date of either the end-date of the on-treatment period or week 52. On-treatment period started with onset date on or after the first dose of trial product and no later than the first date of either the follow-up visit (FU2), the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin or the end-date for the in-trial period. Safety analysis set included all subjects randomly assigned to trial treatment and who took at least 1 dose of trial product.
    End point type
    Secondary
    End point timeframe
    From baseline week 0 (V2) to week 52 (V46)
    End point values
    		 Insulin icodec Insulin glargine
    Number of subjects analysed
    492
    492
    Units: Episodes
        number (not applicable)
    1
    3
    No statistical analyses for this end point

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

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    End point title
    		 Number of clinically significant hypoglycaemic episodes (level 2) (below 3.0 mmol/L (54 mg/dL) confirmed by BG meter)
    End point description
    Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL) confirmed by BG meter) is presented. Clinically significant hypoglycaemia is defined as plasma glucose value of < 3.0 mmol/L (54 mg/dL) confirmed by BG meter. The outcome data was evaluated based on main-on-treatment period. Main-on-treatment period started with onset date on or after the first dose of trial product and no later than the first date of either the end-date of the on-treatment period or week 52. On-treatment period started with onset date on or after the first dose of trial product and no later than the first date of either the follow-up visit (FU2), the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin or the end-date for the in-trial period. Safety analysis set included all subjects randomly assigned to trial treatment and who took at least 1 dose of trial product.
    End point type
    Secondary
    End point timeframe
    From baseline week 0 (V2) to week 52 (V46)
    End point values
    		 Insulin icodec Insulin glargine
    Number of subjects analysed
    492
    492
    Units: Episodes
        number (not applicable)
    143
    75
    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) or severe hypoglycaemic episodes (level 3)

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    End point title
    		 Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL), confirmed by BG meter) or severe hypoglycaemic episodes (level 3)
    End point description
    Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL), confirmed by BG meter) or severe hypoglycaemic episodes (level 3) is presented. Clinically significant hypoglycaemia is defined as plasma glucose value of < 3.0 mmol/L (54 mg/dL). Severe hypoglycaemic episode is defined as hypoglycaemia with severe cognitive impairment requiring external assistance. Outcome data was evaluated based on main-on-treatment period which started with onset date on or after the first dose of trial product and the first date of the end-date of the on-treatment period or week 52. On-treatment period started with onset date on or after first dose of trial product and the first date of either the follow-up visit, the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin or the end-date for in-trial period. Safety analysis set included subjects randomly assigned to trial treatment and who took at least 1 dose of trial product.
    End point type
    Secondary
    End point timeframe
    From baseline week 0 (V2) to week 52 (V46)
    End point values
    		 Insulin icodec Insulin glargine
    Number of subjects analysed
    492
    492
    Units: Episodes
        number (not applicable)
    144
    78
    No statistical analyses for this end point

    Secondary: Number of severe hypoglycaemic episodes (level 3) (From baseline week 0 (V2) to week 83 (V63))

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    End point title
    		 Number of severe hypoglycaemic episodes (level 3) (From baseline week 0 (V2) to week 83 (V63))
    End point description
    Number of severe hypoglycaemic episodes (level 3) is presented. Severe hypoglycaemic episode is defined as hypoglycaemia with severe cognitive impairment requiring external assistance for recovery. The outcome data was evaluated based on on-treatment period. The on-treatment period started at the date of first dose of trial product as recorded on the eCRF, and ended at the first date of any of the following: The end of trial visit (V63), the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin (corresponding to 5 weeks after the end of the dosing interval for both treatment arms) and the end-date for the in-trial observation period. The on-treatment period represented the time period in which a subject was considered exposed to trial product. Safety analysis set included all subjects randomly assigned to trial treatment and who took at least 1 dose of trial product.
    End point type
    Secondary
    End point timeframe
    From baseline week 0 (V2) to week 83 (V63)
    End point values
    		 Insulin icodec Insulin glargine
    Number of subjects analysed
    492
    492
    Units: Episodes
        number (not applicable)
    1
    7
    No statistical analyses for this end point

    Secondary: Number of clinically significant hypoglycaemic episodes (level 2) (below 3.0 mmol/L (54 mg/dL) confirmed by BG meter) (From baseline week 0 (V2) to week 83 (V63))

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    End point title
    		 Number of clinically significant hypoglycaemic episodes (level 2) (below 3.0 mmol/L (54 mg/dL) confirmed by BG meter) (From baseline week 0 (V2) to week 83 (V63))
    End point description
    Number of clinically significant hypoglycaemic episodes (level 2) (<3.0 mmol/L (54 mg/dL) confirmed by BG meter) is presented. Clinically significant hypoglycaemia is defined as plasma glucose value of < 3.0 mmol/L (54 mg/dL) confirmed by BG meter. The outcome data was evaluated based on on-treatment period. The on-treatment period started at the date of first dose of trial product as recorded on the eCRF, and ended at the first date of any of the following: The end of trial visit (V63), the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin (corresponding to 5 weeks after the end of the dosing interval for both treatment arms) and the end-date for the in-trial observation period. The on-treatment period represented the time period in which a subject was considered exposed to trial product. Safety analysis set included all subjects randomly assigned to trial treatment and who took at least 1 dose of trial product.
    End point type
    Secondary
    End point timeframe
    From baseline week 0 (V2) to week 83 (V63)
    End point values
    		 Insulin icodec Insulin glargine
    Number of subjects analysed
    492
    492
    Units: Episodes
        number (not applicable)
    226
    114
    No statistical analyses for this end point

    Secondary: Mean weekly insulin dose

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    End point title
    		 Mean weekly insulin dose
    End point description
    Mean weekly insulin dose from week 50 (V44) to week 52 (V46) is presented. The outcome data was evaluated based on main on treatment period. Main-on-treatment period started with onset date on or after the first dose of trial product and no later than the first date of either the end-date of the on-treatment period or week 52. On-treatment period started with onset date on or after the first dose of trial product and no later than the first date of either the follow-up visit (FU2), the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin or the end-date for the in-trial period. Safety analysis set included all subjects randomly assigned to trial treatment and who took at least 1 dose of trial product. Number of subjects analysed = Subjects with available data for the endpoint.
    End point type
    Secondary
    End point timeframe
    From week 50 (V44) to week 52 (V46)
    End point values
    		 Insulin icodec Insulin glargine
    Number of subjects analysed
    472
    477
    Units: Unit (U) of insulin
        geometric mean (geometric coefficient of variation)
    215.59 ± 77.39
    220.85 ± 76.16
    No statistical analyses for this end point

    Secondary: Number of clinically significant hypoglycaemic episodes (level 2) (below 3.0 mmol/L (54 mg/dL), confirmed by BG meter) or severe hypoglycaemic episodes (level 3) (From baseline week 0 (V2) to week 83 (V63))

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    End point title
    		 Number of clinically significant hypoglycaemic episodes (level 2) (below 3.0 mmol/L (54 mg/dL), confirmed by BG meter) or severe hypoglycaemic episodes (level 3) (From baseline week 0 (V2) to week 83 (V63))
    End point description
    Number of clinically significant hypoglycaemic episodes (level 2) (below 3.0 mmol/L (54 mg/dL), confirmed by BG meter) or severe hypoglycaemic episodes (level 3) is presented. Clinically significant hypoglycaemia is defined as plasma glucose value of below 3.0 mmol/L (54 mg/dL). Severe hypoglycaemic episode is defined as hypoglycaemia with severe cognitive impairment requiring external assistance. Outcome data was evaluated based on on-treatment period. On-treatment period started at date of first dose of trial product as recorded on eCRF and ended at the first date of any of the following: End of trial visit (V63), the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin (corresponding to 5 weeks after the end of dosing interval for both treatment arms) and the end-date for in-trial observation period. Safety analysis set included all subjects randomly assigned to trial treatment and who took at least 1 dose of trial product.
    End point type
    Secondary
    End point timeframe
    From baseline week 0 (V2) to week 83 (V63)
    End point values
    		 Insulin icodec Insulin glargine
    Number of subjects analysed
    492
    492
    Units: Episodes
        number (not applicable)
    227
    121
    No statistical analyses for this end point

    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 week 0 (V2) to week 52 (V46) is presented. The outcome data was evaluated based on the in-trial observation period. The in-trial period started at randomization and ended at the date of: The last direct subject-site contact, withdrawal for subjects who withdrew their informed consent, the last subject-investigator contact as defined by the investigator for subjects who were lost to follow-up (i.e., possibly an unscheduled phone visit), death for subjects who died before any of the above. Full analysis set included all randomized subjects.
    End point type
    Secondary
    End point timeframe
    From baseline week 0 (V2) to week 52 (V46)
    End point values
    		 Insulin icodec Insulin glargine
    Number of subjects analysed
    492
    492
    Units: kilograms (kg)
        least squares mean (standard error)
    2.29 ± 0.21
    1.83 ± 0.21
    No statistical analyses for this end point

    Secondary: Time spent below 3.0 mmol/L (54 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6

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    End point title
    		 Time spent below 3.0 mmol/L (54 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6
    End point description
    Time spent below 3.0 mmol/L (54 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6 from week 48 (V42) to week 52 (V46) was presented. Time spent below threshold is defined as 100 times the number of recorded measurements below the threshold, divided by the total number of recorded measurements. The outcome data was evaluated based on the in-trial observation period. The in-trial period started at randomization and ended at the date of: The last direct subject-site contact, withdrawal for subjects who withdrew their informed consent, the last subject-investigator contact as defined by the investigator for subjects who were lost to follow-up (that is, possibly an unscheduled phone visit), death for subjects who died before any of the above. Full analysis set included all randomized subjects. Number of subjects analysed=Subjects with available data for the endpoint.
    End point type
    Secondary
    End point timeframe
    From week 48 (V42) to week 52 (V46)
    End point values
    		 Insulin icodec Insulin glargine
    Number of subjects analysed
    439
    440
    Units: Percentage of time
        arithmetic mean (standard deviation)
    0.27 ± 0.57
    0.21 ± 0.63
    No statistical analyses for this end point

    Secondary: Time spent greater than 10 mmol/L (180 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6

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    End point title
    		 Time spent greater than 10 mmol/L (180 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6
    End point description
    Time spent greater than 10 mmol/L (180 mg/dL) using continuous glucose monitoring (CGM) system, Dexcom G6 from week 48 (V42) to week 52 (V46) is presented. Time spent above threshold is defined as 100 times the number of recorded measurements above the threshold, divided by the total number of recorded measurements. The outcome data was evaluated based on the in-trial observation period. The in-trial period started at randomization and ended at the date of: The last direct subject-site contact, withdrawal for subjects who withdrew their informed consent, the last participant-investigator contact as defined by the investigator for subjects who were lost to follow-up (i.e., possibly an unscheduled phone visit), death for subjects who died before any of the above. Full analysis set included all randomized subjects. Number of subjects analysed=Subjects with available data for the endpoint.
    End point type
    Secondary
    End point timeframe
    From week 48 (V42) to week 52 (V46)
    End point values
    		 Insulin icodec Insulin glargine
    Number of subjects analysed
    439
    440
    Units: Percentage of time
        arithmetic mean (standard deviation)
    26.86 ± 18.74
    32.27 ± 18.66
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From baseline (week 0) to end of trial (week 83)
    Adverse event reporting additional description
    Safety analysis set included all randomised subjects who were randomly assigned to trial treatment and who took at least 1 dose of trial product. A treatment-emergent AE (TEAE) was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of trial (week 83). All presented AEs are treatment emergent.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24
    Reporting groups
    Reporting group title
    Insulin glargine
    Reporting group description
    		 Subjects received once daily subcutaneous injection of insulin glargine at a starting dose of 10 U using SoloSTAR pre-filled pen injector in combination with non-insulin anti-diabetic drugs. The dose adjustment was based on the three pre-breakfast self-monitored plasma glucose (SMPG) values measured on two days prior to titration and on the day of the contact. If atleast one pre-breakfast SMPG value was: < 4.4 mmol/L: the dose was reduced by 3 U; 4.4-7.2: no dose adjustment required and >7.2 mmol/L: dose was increased by 3 U.

    Reporting group title
    Insulin icodec
    Reporting group description
    		 Subjects received once-weekly subcutaneous injection of insulin icodec at a starting dose of 70 U for 52 weeks using PDS 290 pre-filled injector in combination with non-insulin anti-diabetic drugs. The dose adjustment was based on the three pre-breakfast self-monitored plasma glucose (SMPG) values measured on two days prior to titration and on the day of the contact. If at least one pre-breakfast SMPG value was: < 4.4 millimoles per liter (mmol/L): dose reduced by 20 units (U); 4.4-7.2 mmol/L: no adjustment; > 7.2 mmol/L: dose increased by 20 units.

    Serious adverse events
    		 Insulin glargine Insulin icodec
    Total subjects affected by serious adverse events
         subjects affected / exposed
    72 / 492 (14.63%)
    64 / 492 (13.01%)
         number of deaths (all causes)
    4
    5
         number of deaths resulting from adverse events
    1
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    0 / 492 (0.00%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colon cancer
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatocellular carcinoma
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Glioblastoma multiforme
         subjects affected / exposed
    0 / 492 (0.00%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Lung adenocarcinoma
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastatic renal cell carcinoma
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Metastases to liver
         subjects affected / exposed
    0 / 492 (0.00%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Malignant melanoma in situ
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ovarian cancer metastatic
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic carcinoma metastatic
         subjects affected / exposed
    0 / 492 (0.00%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatic neoplasm
         subjects affected / exposed
    0 / 492 (0.00%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Prostate cancer
         subjects affected / exposed
    1 / 492 (0.20%)
    2 / 492 (0.41%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small cell lung cancer
         subjects affected / exposed
    0 / 492 (0.00%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Arteriosclerosis
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Brachiocephalic arteriosclerosis
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematoma
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (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 / 492 (0.00%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Iliac artery stenosis
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery stenosis
         subjects affected / exposed
    0 / 492 (0.00%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral arterial occlusive disease
         subjects affected / exposed
    2 / 492 (0.41%)
    1 / 492 (0.20%)
         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
    0 / 492 (0.00%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Removal of foreign body
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Death
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Immunisation reaction
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    0 / 492 (0.00%)
    2 / 492 (0.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uterine prolapse
         subjects affected / exposed
    0 / 492 (0.00%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vaginal prolapse
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (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 pulmonary oedema
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    1 / 492 (0.20%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    0 / 492 (0.00%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Psychotic disorder
         subjects affected / exposed
    0 / 492 (0.00%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Cardiac stress test abnormal
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic enzyme increased
         subjects affected / exposed
    1 / 492 (0.20%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Troponin increased
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (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
    Deafness traumatic
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endotracheal intubation complication
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fibula fracture
         subjects affected / exposed
    0 / 492 (0.00%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    0 / 492 (0.00%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower limb fracture
         subjects affected / exposed
    2 / 492 (0.41%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meniscus injury
         subjects affected / exposed
    0 / 492 (0.00%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Periprocedural myocardial infarction
         subjects affected / exposed
    0 / 492 (0.00%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural haemorrhage
         subjects affected / exposed
    0 / 492 (0.00%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural stroke
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Hydrocele
         subjects affected / exposed
    0 / 492 (0.00%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    0 / 492 (0.00%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Acute myocardial infarction
         subjects affected / exposed
    5 / 492 (1.02%)
    4 / 492 (0.81%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    1 / 492 (0.20%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Arteriosclerosis coronary artery
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    1 / 492 (0.20%)
    4 / 492 (0.81%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    2 / 492 (0.41%)
    5 / 492 (1.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    2 / 492 (0.41%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial thrombosis
         subjects affected / exposed
    0 / 492 (0.00%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial flutter
         subjects affected / exposed
    1 / 492 (0.20%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrioventricular block second degree
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (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
    0 / 492 (0.00%)
    2 / 492 (0.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    1 / 492 (0.20%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic coronary syndrome
         subjects affected / exposed
    0 / 492 (0.00%)
    1 / 492 (0.20%)
         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
    2 / 492 (0.41%)
    4 / 492 (0.81%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coronary artery occlusion
         subjects affected / exposed
    0 / 492 (0.00%)
    2 / 492 (0.41%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Left ventricular dysfunction
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (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
    3 / 492 (0.61%)
    3 / 492 (0.61%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus tachycardia
         subjects affected / exposed
    0 / 492 (0.00%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (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
    Carotid artery stenosis
         subjects affected / exposed
    0 / 492 (0.00%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cervical radiculopathy
         subjects affected / exposed
    0 / 492 (0.00%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    0 / 492 (0.00%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoglycaemic unconsciousness
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    0 / 492 (0.00%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolic encephalopathy
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    1 / 492 (0.20%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombotic stroke
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 492 (0.20%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood loss anaemia
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Presbyacusis
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (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 / 492 (0.20%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diabetic retinal oedema
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Optic ischaemic neuropathy
         subjects affected / exposed
    0 / 492 (0.00%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Open angle glaucoma
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Anal fissure
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis ischaemic
         subjects affected / exposed
    0 / 492 (0.00%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal ulcer
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (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
    0 / 492 (0.00%)
    1 / 492 (0.20%)
         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 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    0 / 492 (0.00%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Large intestine polyp
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    1 / 492 (0.20%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Umbilical hernia
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatitis
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic cirrhosis
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Myxoid cyst
         subjects affected / exposed
    0 / 492 (0.00%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urticaria
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ketonuria
         subjects affected / exposed
    0 / 492 (0.00%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal impairment
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureterolithiasis
         subjects affected / exposed
    1 / 492 (0.20%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract obstruction
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 492 (0.00%)
    1 / 492 (0.20%)
         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 / 492 (0.00%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    3 / 492 (0.61%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Plantar fasciitis
         subjects affected / exposed
    0 / 492 (0.00%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal pain
         subjects affected / exposed
    2 / 492 (0.41%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Anal abscess
         subjects affected / exposed
    2 / 492 (0.41%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19 pneumonia
         subjects affected / exposed
    2 / 492 (0.41%)
    4 / 492 (0.81%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    3 / 492 (0.61%)
    4 / 492 (0.81%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Bronchitis
         subjects affected / exposed
    0 / 492 (0.00%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    2 / 492 (0.41%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic hepatitis C
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Empyema
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia urinary tract infection
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    0 / 492 (0.00%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endophthalmitis
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal sepsis
         subjects affected / exposed
    0 / 492 (0.00%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Laryngitis
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteomyelitis chronic
         subjects affected / exposed
    0 / 492 (0.00%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    0 / 492 (0.00%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Otitis media acute
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (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
    3 / 492 (0.61%)
    2 / 492 (0.41%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural infection
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory syncytial virus infection
         subjects affected / exposed
    0 / 492 (0.00%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    2 / 492 (0.41%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Adult failure to thrive
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Electrolyte depletion
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    0 / 492 (0.00%)
    1 / 492 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lactic acidosis
         subjects affected / exposed
    1 / 492 (0.20%)
    0 / 492 (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
    		 Insulin glargine Insulin icodec
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    216 / 492 (43.90%)
    221 / 492 (44.92%)
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    23 / 492 (4.67%)
    27 / 492 (5.49%)
         occurrences all number
    27
    30
    Eye disorders
    Diabetic retinopathy
         subjects affected / exposed
    32 / 492 (6.50%)
    36 / 492 (7.32%)
         occurrences all number
    38
    41
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    26 / 492 (5.28%)
    39 / 492 (7.93%)
         occurrences all number
    29
    54
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    22 / 492 (4.47%)
    30 / 492 (6.10%)
         occurrences all number
    28
    36
    Back pain
         subjects affected / exposed
    32 / 492 (6.50%)
    40 / 492 (8.13%)
         occurrences all number
    34
    42
    Infections and infestations
    COVID-19
         subjects affected / exposed
    101 / 492 (20.53%)
    87 / 492 (17.68%)
         occurrences all number
    108
    91
    Upper respiratory tract infection
         subjects affected / exposed
    22 / 492 (4.47%)
    28 / 492 (5.69%)
         occurrences all number
    24
    40
    Nasopharyngitis
         subjects affected / exposed
    47 / 492 (9.55%)
    38 / 492 (7.72%)
         occurrences all number
    56
    50

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    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
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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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