A Research Study to Compare a New Weekly Insulin, Insulin Icodec, and an Available Daily Insulin, Insulin Degludec, Both in Combination With Mealtime Insulin in People With Type 1 Diabetes (ONWARDS 6)

Efficacy and Safety of Once Weekly Insulin Icodec Compared to Once Daily Insulin Degludec 100 Units/mL, Both in Combination With Insulin Aspart, in Adults With Type 1 Diabetes. A 26-week, Randomised, Multicentre, Open-label, Active-controlled, Parallel Group, Two Armed, Treat-to-target Trial Investigating the Effect on Glycaemic Control and Safety of Treatment With Once Weekly Insulin Icodec Compared to Once Daily Insulin Degludec, Both in Combination With Insulin Aspart in Adults With Type 1 Diabetes, With a 26-week Extension Investigating Long Term Safety

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04848480

Acronym

ONWARDS 6

Enrollment

582

Registered

2021-04-19

Start date

2021-04-30

Completion date

2022-12-02

Last updated

2025-12-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Diabetes Mellitus, Type 1

Brief summary

This study compares insulin icodec (a new insulin) to insulin degludec (an insulin already available on the market) in people with type 1 diabetes. The study will look at how well insulin icodec taken weekly controls blood sugar compared to insulin degludec taken daily. Participants will either get insulin icodec that participants will have to inject once a week on the same day of the week, or insulin degludec that participants will have to inject once a day at the same time every day. Which treatment participants get is decided at random. Participants will also get a mealtime insulin. The insulin is injected with a needle in a skin fold in the thigh, upper arm or stomach. The study will last for about 1 year and 2 months. Participants will have 28 clinic visits and 28 phone calls with the study doctor. At 11 clinic visits participants will have blood samples taken. At 6 clinic visits participants cannot eat or drink (except for water) for 8 hours before the visit. Participants will be asked to wear a sensor that measures your blood sugar all the time. Participants will be asked to wear it for a total of 57 weeks (around 1 year). Women cannot take part if pregnant, breast-feeding or plan to become pregnant during the study period.

Interventions

DRUGinsulin icodec

insulin icodec 700 units/mL, subcutaneously (under the skin), solution for injection once weekly

DRUGinsulin degludec

insulin degludec 100 units/mL, subcutaneously (under the skin), solution for injection once daily

DRUGinsulin aspart

insulin aspart 100 units/mL, subcutaneously (under the skin), solution for injection daily

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Male or female aged greater than or equal to 18 years at the time of signing informed consent. * Diagnosed with type 1 diabetes mellitus greater than or equal to 1 year prior to the day of screening. * Treated with multiple daily insulin injections (basal and bolus insulin analogue regimes) greater than or equal to 1 year prior to the day of screening. * HbA1c below10% at screening visit based on analysis from central laboratory.

Exclusion criteria

* Myocardial infarction, stroke, hospitalization for unstable angina pectoris or transient ischaemic attack within 180 days prior to the day of screening. * Chronic heart failure classified as New York Heart Association (NYHA) Class IV at screening. * Anticipated initiation or change in concomitant medications (for more than 14 consecutive days) known to affect weight or glucose metabolism (e.g. treatment with orlistat, thyroid hormones, or corticosteroids). * Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days prior to screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.

Design outcomes

Primary

Measure	Time frame	Description
Change in Glycosylated Haemoglobin (HbA1c) at Week 26	Baseline (week 0), week 26	Change in HbA1c from baseline to week 26 is presented. Data is reported for 'in-trial' period. In-trial observation period started at randomisation and ended at the date of: the last direct participant-site contact; withdrawal for participants who withdrew their informed consent; the last participant-investigator contact as defined by the investigator for participants who were lost to follow-up (i.e. possibly an unscheduled phone visit); death for participants who died before any of the above.

Secondary

Measure	Time frame	Description
Change in Fasting Plasma Glucose (FPG)	Baseline (week 0), week 26	Change in FPG from baseline to week 26 is presented. Data is reported for 'in-trial' period. In-trial observation period started at randomisation and ended at the date of: the last direct participant-site contact; withdrawal for participants who withdrew their informed consent; the last participant-investigator contact as defined by the investigator for participants who were lost to follow-up (i.e. possibly an unscheduled phone visit); death for participants who died before any of the above.
Percentage of Time in Range 3.9-10.0 mmol/L (70-180 Milligrams Per Deciliter [mg/dL]) Using Continuous Glucose Monitoring (CGM) System	From week 22 to week 26	Percentage of time in range 3.9-10.0 mmol/L (70-180 mg/dL) using CGM system from week 22 to week 26 is presented. Time in range is defined as 100 times the number of recorded measurements in glycaemic range 3.9-10.0 mmol/L (70-180 mg/dL), both inclusive, divided by the total number of recorded measurements. Data is reported for 'in-trial' period. In-trial observation period started at randomisation and ended at the date of: the last direct participant-site contact; withdrawal for participants who withdrew their informed consent; the last participant-investigator contact as defined by the investigator for participants who were lost to follow-up (i.e. possibly an unscheduled phone visit); death for participants who died before any of the above.
Change in Diabetes Treatment Satisfaction Questionnaire (DTSQs) in Total Treatment Satisfaction	Baseline (week 0), week 26	Change in DTSQs in total treatment satisfaction from baseline to week 26 is presented. The sum score for DTSQ in total treatment satisfaction was calculated by adding the six item scores of items 1, 4, 5, 6, 7 and 8. The sum score for DTSQ can range from 0 to 36, with 0 being the lowest and 36 being the highest score in total treatment satisfaction. Higher scores on the DTSQ total score indicate higher treatment satisfaction. Data is reported for 'in-trial' period. In-trial observation period started at randomisation and ended at the date of: the last direct participant-site contact; withdrawal for participants who withdrew their informed consent; the last participant-investigator contact as defined by the investigator for participants who were lost to follow-up (i.e. possibly an unscheduled phone visit); death for participants who died before any of the above.
Number of Severe Hypoglycaemic Episodes (Level 3): From Baseline (Week 0) to Week 26	From baseline (week 0) to week 26	Number of severe hypoglycaemic episodes (level 3) from baseline to week 26 are presented. Severe hypoglycaemia (level 3) is defined as hypoglycaemia with severe cognitive impairment requiring external assistance for recovery. Data is reported for 'main-on-treatment' period. The main-on-treatment period started at the date of first dose of trial product as recorded on the electronic case report form (eCRF), and ended at the first date of any of the following: the end date of the on-treatment period; week 26. On-treatment: Onset date on or after the first dose of trial product and no later than 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 the in-trial period. Data reflects total number of episodes across all participants within the arm.
Number of Severe Hypoglycaemic Episodes (Level 3): From Baseline (Week 0) to Week 57	From baseline (week 0) to week 57	Number of severe hypoglycaemic episodes (level 3) from baseline to week 57 are presented. Severe hypoglycaemia (level 3) is defined as hypoglycaemia with severe cognitive impairment requiring external assistance for recovery. Data is reported for 'on-treatment' period. The on-treatment period: 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. Data reflects total number of episodes across all participants within the arm.
Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (Less Than 3.0 mmol/L (54 mg/dL) Confirmed by Blood Glucose [BG] Meter): From Baseline (Week 0) to Week 26	From baseline (week 0) to week 26	Number of clinically significant hypoglycaemic episodes (level 2) from baseline to week 26 are presented. Clinically significant hypoglycaemia (level 2) is defined as plasma glucose value of less than (\<) 3.0 mmol/L (54 mg/dL) confirmed by BG meter. Data is reported for 'main-on-treatment' period. The main-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 date of the on-treatment period; week 26. The on-treatment period: 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. Data reflects total number of episodes across all participants within the arm.
Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (Less Than 3.0 mmol/L (54 mg/dL) Confirmed by BG Meter): From Baseline (Week 0) to Week 57	From baseline (week 0) to week 57	Number of clinically significant hypoglycaemic episodes (level 2) from baseline to week 57 are presented. Clinically significant hypoglycaemia (level 2) is defined as plasma glucose value of less than (\<) 3.0 mmol/L (54 mg/dL) confirmed by BG meter. Data is reported for 'on-treatment' period. The on-treatment period: 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. Data reflects total number of episodes across all participants within the arm.
Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (Less Than 3.0 mmol/L (54 mg/dL), Confirmed by BG Meter) or Severe Hypoglycaemic Episodes (Level 3): From Baseline (Week 0) to Week 26	From baseline (week 0) to week 26	Number of clinically significant hypoglycaemic episodes (level 2) or severe hypoglycaemic episodes (level 3) from baseline to week 26 presented. Clinically significant hypoglycaemia (level 2) is de-fined as plasma glucose value of \< 3.0 mmol/L (54 mg/dL) confirmed by BG meter. Severe hypo-glycaemia (level 3) is defined as hypoglycaemia with severe cognitive impairment requiring ex-ternal assistance for recovery. Data is reported for 'main-on-treatment' period, started at date of first dose of trial product as recorded on eCRF, and ended at first date of any of following: end date of on-treatment period; week 26. On-treatment period: Onset date on or after the first dose of trial product and no later than 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. Data reflects total number of episodes across all participants within the arm.
Change in Glycosylated Haemoglobin (HbA1c) at Week 52	Baseline (week 0), week 52	Change in HbA1c from baseline to week 52 is presented. Data is reported for 'in-trial' period. In-trial observation period started at randomisation and ended at the date of: the last direct participant-site contact; withdrawal for participants who withdrew their informed consent; the last participant-investigator contact as defined by the investigator for participants who were lost to follow-up (i.e. possibly an unscheduled phone visit); death for participants who died before any of the above.
Number of Nocturnal Clinically Significant Hypoglycaemic Episodes (Level 2) (Less Than 3.0 mmol/L (54 mg/dL), Confirmed by BG Meter) or Severe Hypoglycaemic Episodes (Level 3): From Baseline (Week 0) to Week 26	From baseline (week 0) to week 26	Number of nocturnal clinically significant hypoglycaemic episodes (level 2) or severe hypogly-caemic episodes (level 3) from baseline to week 26 presented. Nocturnal: Period between 00:01 and 05:59 (both included). Clinically significant hypoglycaemia (level 2): Plasma glucose value of \< 3.0 mmol/L (54 mg/dL) confirmed by BG meter. Severe hypoglycaemia (level 3): Hypoglycaemia with severe cognitive impairment requiring external assistance for recovery. Data is reported for 'main-on-treatment' period, started at date of first dose of trial product as recorded on eCRF, and ended at first date of any of following: end date of on-treatment period; week 26. On-treatment period: Onset date on or after first dose of trial product and no later than first date of either fol-low-up visit, last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin or end-date for in-trial period. Data reflects total number of episodes across all participants within the arm.
Number of Nocturnal Clinically Significant Hypoglycaemic Episodes (Level 2) (Less Than 3.0 mmol/L (54 mg/dL), Confirmed by BG Meter) or Severe Hypoglycaemic Episodes (Level 3): From Baseline (Week 0) to Week 57	From baseline (week 0) to week 57	Number of nocturnal clinically significant hypoglycaemic episodes (level 2) or severe hypoglycaemic episodes (level 3) from baseline to week 57 are presented. Nocturnal: The period between 00:01 and 05:59 (both included). Clinically significant hypoglycaemia (level 2): Plasma glucose value of \< 3.0 mmol/L (54 mg/dL) confirmed by BG meter. Severe hypoglycaemia (level 3): Hypoglycaemia with severe cognitive impairment requiring external assistance for recovery. Data is reported for 'on-treatment' period. The on-treatment period: 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. Data reflects total number of episodes across all participants within the arm.
Mean Total Weekly Insulin Dose: From Week 24 to Week 26	From week 24 to week 26	Mean total weekly insulin dose from week 24 to week 26 is presented. Data is reported for 'main-on-treatment' period. The main-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 date of the on-treatment period; week 26. The on-treatment period: 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.
Percentage of Time Spent Less Than (<) 3.0 mmol/L (54 mg/dL) Using Continuous Glucose Monitoring (CGM) System	From week 22 to week 26	Percentage of time spent \< 3.0 mmol/L using CGM system from week 22 to week 26 is presented. Time spent below threshold (\< 3.0 mmol/L \[54 mg/dL\]) was defined as 100 times the number of recorded measurements below the threshold, divided by the total number of recorded measurements. Data is reported for 'in-trial' period. In-trial observation period started at randomisation and ended at the date of: the last direct participant-site contact; withdrawal for participants who withdrew their informed consent; the last participant-investigator contact as defined by the investigator for participants who were lost to follow-up (i.e. possibly an unscheduled phone visit); death for participants who died before any of the above.
Percentage of Time Spent Greater Than (>) 10 mmol/L (180 mg/dL) Using Continuous Glucose Monitoring (CGM) System	From week 22 to week 26	Percentage of time spent \> 10 mmol/L using CGM system from week 22 to week 26 is presented. Time spent above threshold (\> 10 mmol/L \[180 mg/dL\]) was defined as 100 times the number of recorded measurements above the threshold, divided by the total number of recorded measurements. Data is reported for 'in-trial' period. In-trial observation period started at randomisation and ended at the date of: the last direct participant-site contact; withdrawal for participants who withdrew their informed consent; the last participant-investigator contact as defined by the investigator for participants who were lost to follow-up (i.e. possibly an unscheduled phone visit); death for participants who died before any of the above.
Mean Total Weekly Insulin Dose: From Week 50 to Week 52	From week 50 to week 52	Mean total weekly insulin dose from week 50 to week 52 is presented. Data is reported for 'on-treatment' period. The on-treatment period: 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.
Change in Body Weight	Baseline (week 0), week 26	Change in body weight from baseline to week 26 is presented. Data is reported for 'in-trial' period. In-trial observation period started at randomisation and ended at the date of: the last direct participant-site contact; withdrawal for participants who withdrew their informed consent; the last participant-investigator contact as defined by the investigator for participants who were lost to follow-up (i.e. possibly an unscheduled phone visit); death for participants who died before any of the above.
Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (Less Than 3.0 mmol/L (54 mg/dL), Confirmed by BG Meter) or Severe Hypoglycaemic Episodes (Level 3): From Baseline (Week 0) to Week 57	From baseline (week 0) to week 57	Number of clinically significant hypoglycaemic episodes (level 2) or severe hypoglycaemic episodes (level 3) from baseline to week 57 are presented. Clinically significant hypoglycaemia (level 2) is defined as plasma glucose value of less than (\<) 3.0 mmol/L (54 mg/dL) confirmed by BG meter. Severe hypoglycaemia (level 3) is defined as hypoglycaemia with severe cognitive impairment requiring external assistance for recovery. Data is reported for 'on-treatment' period. The on-treatment period: 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. Data reflects total number of episodes across all participants within the arm.

Countries

Austria, Canada, Germany, India, Italy, Japan, Netherlands, Russia, Spain, Turkey (Türkiye), United Kingdom, United States

Participant flow

Recruitment details

The trial was conducted at 97 sites in 12 countries as follows (number of sites that screened subjects/ number of sites that randomized subject): Austria-(6/6), Canada-(5/5), Germany-(8/8), India-(6/6), Italy-(5/5), Japan-(7/7), Netherlands-(3/3), Russia-(10/10), Spain-(4/4), Turkey-(7/7), United Kingdom-(8/8), United States-(29/28).

Pre-assignment details

This was a 52-week trial. The first 26 weeks of the trial constituted the main phase which was followed by a 26-week extension phase with focus on evaluating long term safety and provide long-term exposure data.

Participants by arm

Arm	Count
Insulin Icodec + Insulin Aspart Participants received Insulin icodec along with Insulin aspart for 52 weeks subcutaneously. Participants received once weekly subcutaneous (s.c.) injection of Insulin icodec using PDS290 prefilled pen-injector at a starting dose of 7 times the pre-trial total daily basal insulin dose + 50% or 100% of their 7 times total daily basal insulin dose depending on insulin regime and HbA1c level. The following weekly dose was 7 times the total daily dose of the respective participants ('unit to unit switch' approach: current daily dose x 7). 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 reduced by 20 U; 4.4-7.2 mmol/L: no adjustment; \> 7.2 mmol/L: dose increased by 20 U. Dose titration of insulin aspart was based on the respective premeal(s) and bedtime self-measured plasma glucose (SMPG) measured weekly.	290
Insulin Degludec + Insulin Aspart Participants received Insulin degludec along with Insulin aspart for 52 weeks subcutaneously. Participants received once daily s.c. injection of Insulin degludec using PDS290 prefilled pen-injector at a dose in accordance with local label. Participants were to perform once daily 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 millimoles per liter (mmol/L): dose reduced by 3 units (U); 4.4-7.2 mmol/L: no adjustment; \> 7.2 mmol/L: dose increased by 3 U. Dose titration of insulin aspart was based on the respective premeal(s) and bedtime SMPG measured weekly.	292
Total	582

Withdrawals & dropouts

Period	Reason	FG000	FG001
Extension Phase (26 Weeks)	Lost to Follow-up	0	1
Extension Phase (26 Weeks)	Physician Decision	1	0
Extension Phase (26 Weeks)	Withdrawal by Subject	4	2
Main Phase (26 Weeks)	Death	1	0
Main Phase (26 Weeks)	Lost to Follow-up	1	1
Main Phase (26 Weeks)	Withdrawal by Subject	9	7

Baseline characteristics

Characteristic	Insulin Degludec + Insulin Aspart	Total	Insulin Icodec + Insulin Aspart
Age, Continuous	44.28 years STANDARD_DEVIATION 14.07	44.18 years STANDARD_DEVIATION 14.06	44.08 years STANDARD_DEVIATION 14.07
Ethnicity (NIH/OMB) Hispanic or Latino	10 Participants	20 Participants	10 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	282 Participants	562 Participants	280 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Race Asian	72 Participants	123 Participants	51 Participants
Race/Ethnicity, Customized Race Black Or African American	2 Participants	11 Participants	9 Participants
Race/Ethnicity, Customized Race White	218 Participants	448 Participants	230 Participants
Sex: Female, Male Female	120 Participants	245 Participants	125 Participants
Sex: Female, Male Male	172 Participants	337 Participants	165 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	1 / 290	0 / 292
other Total, other adverse events	145 / 290	162 / 292
serious Total, serious adverse events	24 / 290	20 / 292

Outcome results

Primary

Change in Glycosylated Haemoglobin (HbA1c) at Week 26

Change in HbA1c from baseline to week 26 is presented. Data is reported for 'in-trial' period. In-trial observation period started at randomisation and ended at the date of: the last direct participant-site contact; withdrawal for participants who withdrew their informed consent; the last participant-investigator contact as defined by the investigator for participants who were lost to follow-up (i.e. possibly an unscheduled phone visit); death for participants who died before any of the above.

Time frame: Baseline (week 0), week 26

Population: Full analysis set included all randomised participants.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Insulin Icodec + Insulin Aspart	Change in Glycosylated Haemoglobin (HbA1c) at Week 26	-0.47 Percentage of HbA1c	Standard Error 0.07
Insulin Degludec + Insulin Aspart	Change in Glycosylated Haemoglobin (HbA1c) at Week 26	-0.51 Percentage of HbA1c	Standard Error 0.06

Comparison: Change from baseline in HbA1c after 26 weeks was analysed using ANCOVA model with treatment, region, HbA1c group at screening and pre-trial basal insulin treatment as fixed factors, and baseline response as covariate.p-value: 0.006595% CI: [-0.13, 0.23]ANCOVA

Secondary

Change in Body Weight

Change in body weight from baseline to week 26 is presented. Data is reported for 'in-trial' period. In-trial observation period started at randomisation and ended at the date of: the last direct participant-site contact; withdrawal for participants who withdrew their informed consent; the last participant-investigator contact as defined by the investigator for participants who were lost to follow-up (i.e. possibly an unscheduled phone visit); death for participants who died before any of the above.

Time frame: Baseline (week 0), week 26

Population: Full analysis set included all randomised participants.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Insulin Icodec + Insulin Aspart	Change in Body Weight	1.29 kilograms	Standard Error 0.23
Insulin Degludec + Insulin Aspart	Change in Body Weight	1.01 kilograms	Standard Error 0.23

Secondary

Change in Diabetes Treatment Satisfaction Questionnaire (DTSQs) in Total Treatment Satisfaction

Change in DTSQs in total treatment satisfaction from baseline to week 26 is presented. The sum score for DTSQ in total treatment satisfaction was calculated by adding the six item scores of items 1, 4, 5, 6, 7 and 8. The sum score for DTSQ can range from 0 to 36, with 0 being the lowest and 36 being the highest score in total treatment satisfaction. Higher scores on the DTSQ total score indicate higher treatment satisfaction. Data is reported for 'in-trial' period. In-trial observation period started at randomisation and ended at the date of: the last direct participant-site contact; withdrawal for participants who withdrew their informed consent; the last participant-investigator contact as defined by the investigator for participants who were lost to follow-up (i.e. possibly an unscheduled phone visit); death for participants who died before any of the above.

Time frame: Baseline (week 0), week 26

Population: Full analysis set included all randomised participants. Overall Number of Participants Analyzed = participants with available data.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Insulin Icodec + Insulin Aspart	Change in Diabetes Treatment Satisfaction Questionnaire (DTSQs) in Total Treatment Satisfaction	1.97 Score on a scale	Standard Error 0.27
Insulin Degludec + Insulin Aspart	Change in Diabetes Treatment Satisfaction Questionnaire (DTSQs) in Total Treatment Satisfaction	3.06 Score on a scale	Standard Error 0.27

Secondary

Change in Fasting Plasma Glucose (FPG)

Change in FPG from baseline to week 26 is presented. Data is reported for 'in-trial' period. In-trial observation period started at randomisation and ended at the date of: the last direct participant-site contact; withdrawal for participants who withdrew their informed consent; the last participant-investigator contact as defined by the investigator for participants who were lost to follow-up (i.e. possibly an unscheduled phone visit); death for participants who died before any of the above.

Time frame: Baseline (week 0), week 26

Population: Full analysis set included all randomised participants. Overall Number of Participants Analyzed = participants with available data.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Insulin Icodec + Insulin Aspart	Change in Fasting Plasma Glucose (FPG)	-0.84 millimoles per liter (mmol/l)	Standard Error 0.2
Insulin Degludec + Insulin Aspart	Change in Fasting Plasma Glucose (FPG)	-1.87 millimoles per liter (mmol/l)	Standard Error 0.2

Secondary

Change in Glycosylated Haemoglobin (HbA1c) at Week 52

Change in HbA1c from baseline to week 52 is presented. Data is reported for 'in-trial' period. In-trial observation period started at randomisation and ended at the date of: the last direct participant-site contact; withdrawal for participants who withdrew their informed consent; the last participant-investigator contact as defined by the investigator for participants who were lost to follow-up (i.e. possibly an unscheduled phone visit); death for participants who died before any of the above.

Time frame: Baseline (week 0), week 52

Population: Full analysis set included all randomised participants.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Insulin Icodec + Insulin Aspart	Change in Glycosylated Haemoglobin (HbA1c) at Week 52	-0.37 Percentage of HbA1c	Standard Error 0.05
Insulin Degludec + Insulin Aspart	Change in Glycosylated Haemoglobin (HbA1c) at Week 52	-0.54 Percentage of HbA1c	Standard Error 0.05

Secondary

Mean Total Weekly Insulin Dose: From Week 24 to Week 26

Mean total weekly insulin dose from week 24 to week 26 is presented. Data is reported for 'main-on-treatment' period. The main-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 date of the on-treatment period; week 26. The on-treatment period: 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.

Time frame: From week 24 to week 26

Population: Full analysis set included all randomised participants. Overall Number of Participants Analyzed = participants with available data.

Arm	Measure	Value (LEAST_SQUARES_MEAN)
Insulin Icodec + Insulin Aspart	Mean Total Weekly Insulin Dose: From Week 24 to Week 26	310.52 Units of insulin
Insulin Degludec + Insulin Aspart	Mean Total Weekly Insulin Dose: From Week 24 to Week 26	322.68 Units of insulin

Secondary

Mean Total Weekly Insulin Dose: From Week 50 to Week 52

Mean total weekly insulin dose from week 50 to week 52 is presented. Data is reported for 'on-treatment' period. The on-treatment period: 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.

Time frame: From week 50 to week 52

Population: Full analysis set included all randomised participants. Overall Number of Participants Analyzed = participants with available data.

Arm	Measure	Value (LEAST_SQUARES_MEAN)
Insulin Icodec + Insulin Aspart	Mean Total Weekly Insulin Dose: From Week 50 to Week 52	310.14 Units of insulin
Insulin Degludec + Insulin Aspart	Mean Total Weekly Insulin Dose: From Week 50 to Week 52	328.90 Units of insulin

Secondary

Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (Less Than 3.0 mmol/L (54 mg/dL) Confirmed by BG Meter): From Baseline (Week 0) to Week 57

Number of clinically significant hypoglycaemic episodes (level 2) from baseline to week 57 are presented. Clinically significant hypoglycaemia (level 2) is defined as plasma glucose value of less than (\<) 3.0 mmol/L (54 mg/dL) confirmed by BG meter. Data is reported for 'on-treatment' period. The on-treatment period: 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. Data reflects total number of episodes across all participants within the arm.

Time frame: From baseline (week 0) to week 57