Trial Outcomes & Findings for A Research Study to Compare Two Types of Insulin, a New Weekly Insulin, Insulin Icodec and an Available Daily Insulin, Insulin Glargine, Both in Combination With Mealtime Insulin, in People With Type 2 Diabetes Who Use Daily Insulin and Mealtime Insulin (ONWARDS 4) (NCT NCT04880850)

Last Updated: 2025-12-04

Results Overview

Change in HbA1c from baseline (week 0) to week 26 is presented. The outcome data was evaluated based on the in-trial observation 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) and death for participants who died before any of the above.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

582 participants

Primary outcome timeframe

Baseline (week 0), Week 26

Results posted on

2025-12-04

Participant Flow

The trial was conducted at 83 sites in 9 countries as follows: Belgium (5), India (9), Italy (6), Japan (9), Mexico (3), Netherlands (5), Romania (6), Russia (10), United States (30).

The trial duration is approximately 33 weeks, consisting of a 2-week screening period, followed by a 26-week randomised treatment period and a 5-week follow-up period.

Participant milestones

Participant milestones
Measure	Insulin Icodec Participants were to receive once weekly subcutaneous (s.c.) injection of Insulin icodec for 26 weeks, using PDS290 prefilled pen-injector in combination with insulin aspart at a starting dose of 7 times the pre-trial total daily basal insulin dose + 50% of their 7 times total daily basal insulin dose. 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: lesser than (\<) 4.4 millimoles per liter (mmol/L): dose reduced by 20 units (U); 4.4-7.2 mmol/L: no adjustment; greater than (\>) 7.2 mmol/L: dose increased by 20 U. Dose titration of insulin aspart was based on the respective premeal(s) and bedtime SMPG measured.	Insulin Glargine Participants were to receive once daily s.c. injection of Insulin glargine for 26 weeks, using SoloSTAR pre-filled pen-injector in combination with insulin aspart. Participants were to perform 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 mmol/L: dose reduced by 3 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.
Overall Study STARTED	291	291
Overall Study Full Analysis Set (FAS)	291	291
Overall Study Safety Analysis Set (SAS)	291	291
Overall Study COMPLETED	275	273
Overall Study NOT COMPLETED	16	18

Reasons for withdrawal

Reasons for withdrawal
Measure	Insulin Icodec Participants were to receive once weekly subcutaneous (s.c.) injection of Insulin icodec for 26 weeks, using PDS290 prefilled pen-injector in combination with insulin aspart at a starting dose of 7 times the pre-trial total daily basal insulin dose + 50% of their 7 times total daily basal insulin dose. 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: lesser than (\<) 4.4 millimoles per liter (mmol/L): dose reduced by 20 units (U); 4.4-7.2 mmol/L: no adjustment; greater than (\>) 7.2 mmol/L: dose increased by 20 U. Dose titration of insulin aspart was based on the respective premeal(s) and bedtime SMPG measured.	Insulin Glargine Participants were to receive once daily s.c. injection of Insulin glargine for 26 weeks, using SoloSTAR pre-filled pen-injector in combination with insulin aspart. Participants were to perform 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 mmol/L: dose reduced by 3 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.
Overall Study Death	2	1
Overall Study Lost to Follow-up	3	6
Overall Study Physician Decision	2	1
Overall Study Withdrawal by Subject	9	10

Baseline Characteristics

A Research Study to Compare Two Types of Insulin, a New Weekly Insulin, Insulin Icodec and an Available Daily Insulin, Insulin Glargine, Both in Combination With Mealtime Insulin, in People With Type 2 Diabetes Who Use Daily Insulin and Mealtime Insulin (ONWARDS 4)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Insulin Icodec n=291 Participants Participants were to receive once weekly subcutaneous (s.c.) injection of Insulin icodec for 26 weeks, using PDS290 prefilled pen-injector in combination with insulin aspart at a starting dose of 7 times the pre-trial total daily basal insulin dose + 50% of their 7 times total daily basal insulin dose. 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: lesser than (\<) 4.4 millimoles per liter (mmol/L): dose reduced by 20 units (U); 4.4-7.2 mmol/L: no adjustment; greater than (\>) 7.2 mmol/L: dose increased by 20 U. Dose titration of insulin aspart was based on the respective premeal(s) and bedtime SMPG measured.	Insulin Glargine n=291 Participants Participants were to receive once daily s.c. injection of Insulin glargine for 26 weeks, using SoloSTAR pre-filled pen-injector in combination with insulin aspart. Participants were to perform 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 mmol/L: dose reduced by 3 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.	Total n=582 Participants Total of all reporting groups
Age, Continuous	59.67 Years STANDARD_DEVIATION 10.13 • n=3 Participants	59.91 Years STANDARD_DEVIATION 9.92 • n=3 Participants	59.79 Years STANDARD_DEVIATION 10.02 • n=6 Participants
Sex: Female, Male Female	137 Participants n=3 Participants	141 Participants n=3 Participants	278 Participants n=6 Participants
Sex: Female, Male Male	154 Participants n=3 Participants	150 Participants n=3 Participants	304 Participants n=6 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	52 Participants n=3 Participants	53 Participants n=3 Participants	105 Participants n=6 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	239 Participants n=3 Participants	237 Participants n=3 Participants	476 Participants n=6 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=3 Participants	1 Participants n=3 Participants	1 Participants n=6 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=3 Participants	1 Participants n=3 Participants	1 Participants n=6 Participants
Race (NIH/OMB) Asian	95 Participants n=3 Participants	93 Participants n=3 Participants	188 Participants n=6 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=3 Participants	1 Participants n=3 Participants	1 Participants n=6 Participants
Race (NIH/OMB) Black or African American	13 Participants n=3 Participants	8 Participants n=3 Participants	21 Participants n=6 Participants
Race (NIH/OMB) White	183 Participants n=3 Participants	187 Participants n=3 Participants	370 Participants n=6 Participants
Race (NIH/OMB) More than one race	0 Participants n=3 Participants	0 Participants n=3 Participants	0 Participants n=6 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=3 Participants	1 Participants n=3 Participants	1 Participants n=6 Participants

PRIMARY outcome

Timeframe: Baseline (week 0), Week 26

Population: Full analysis set included all randomised participants.

Outcome measures

Outcome measures
Measure	Insulin Icodec n=291 Participants Participants were to receive once weekly subcutaneous (s.c.) injection of Insulin icodec for 26 weeks, using PDS290 prefilled pen-injector in combination with insulin aspart at a starting dose of 7 times the pre-trial total daily basal insulin dose + 50% of their 7 times total daily basal insulin dose. 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: lesser than (\<) 4.4 millimoles per liter (mmol/L): dose reduced by 20 units (U); 4.4-7.2 mmol/L: no adjustment; greater than (\>) 7.2 mmol/L: dose increased by 20 U. Dose titration of insulin aspart was based on the respective premeal(s) and bedtime SMPG measured.	Insulin Glargine n=291 Participants Participants were to receive once daily s.c. injection of Insulin glargine for 26 weeks, using SoloSTAR pre-filled pen-injector in combination with insulin aspart. Participants were to perform 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 mmol/L: dose reduced by 3 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.
Change in Glycated Haemoglobin (HbA1c)	-1.16 Percentage (%) of HbA1c Standard Error 0.05	-1.18 Percentage (%) of HbA1c Standard Error 0.05

SECONDARY outcome

Timeframe: Baseline (week 0), Week 26

Population: Full analysis set included all randomised participants. Overall number of participants analyzed = participants with available data for this outcome measure.

Change in FPG from baseline (week 0) to week 26 is presented. The outcome data was evaluated based on the in-trial observation 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) and death for participants who died before any of the above.

Outcome measures

Outcome measures
Measure	Insulin Icodec n=283 Participants Participants were to receive once weekly subcutaneous (s.c.) injection of Insulin icodec for 26 weeks, using PDS290 prefilled pen-injector in combination with insulin aspart at a starting dose of 7 times the pre-trial total daily basal insulin dose + 50% of their 7 times total daily basal insulin dose. 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: lesser than (\<) 4.4 millimoles per liter (mmol/L): dose reduced by 20 units (U); 4.4-7.2 mmol/L: no adjustment; greater than (\>) 7.2 mmol/L: dose increased by 20 U. Dose titration of insulin aspart was based on the respective premeal(s) and bedtime SMPG measured.	Insulin Glargine n=284 Participants Participants were to receive once daily s.c. injection of Insulin glargine for 26 weeks, using SoloSTAR pre-filled pen-injector in combination with insulin aspart. Participants were to perform 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 mmol/L: dose reduced by 3 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.
Change in Fasting Plasma Glucose (FPG)	-1.75 Millimoles per liter (mmol/L) Standard Error 0.16	-1.61 Millimoles per liter (mmol/L) Standard Error 0.16

SECONDARY outcome

Timeframe: From week 22 to week 26

Population: Full analysis set included all randomised participants. Overall number of participants analyzed = participants with available data for this outcome measure.

Percentage of time in target-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 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 outcome data was evaluated based on the in-trial observation 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) and death for participants who died before any of the above.

Outcome measures

Outcome measures
Measure	Insulin Icodec n=244 Participants Participants were to receive once weekly subcutaneous (s.c.) injection of Insulin icodec for 26 weeks, using PDS290 prefilled pen-injector in combination with insulin aspart at a starting dose of 7 times the pre-trial total daily basal insulin dose + 50% of their 7 times total daily basal insulin dose. 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: lesser than (\<) 4.4 millimoles per liter (mmol/L): dose reduced by 20 units (U); 4.4-7.2 mmol/L: no adjustment; greater than (\>) 7.2 mmol/L: dose increased by 20 U. Dose titration of insulin aspart was based on the respective premeal(s) and bedtime SMPG measured.	Insulin Glargine n=237 Participants Participants were to receive once daily s.c. injection of Insulin glargine for 26 weeks, using SoloSTAR pre-filled pen-injector in combination with insulin aspart. Participants were to perform 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 mmol/L: dose reduced by 3 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.
Percentage of Time in Target-range 3.9-10.0 mmol/L (70-180 mg/dL) Using Continuous Glucose Monitoring (CGM) System	66.88 Percentage (%) of time Standard Deviation 15.62	66.44 Percentage (%) of time Standard Deviation 16.17

SECONDARY outcome

Timeframe: From baseline (week 0) to week 31

Population: Safety analysis set included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.

Severe hypoglycaemic episodes (level 3) were defined as episodes that were associated with severe cognitive impairment requiring external assistance for recovery. The outcome data was evaluated based on the on-treatment observation period. The on-treatment observation 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 of trial visit, 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.

Outcome measures

Outcome measures
Measure	Insulin Icodec n=291 Participants Participants were to receive once weekly subcutaneous (s.c.) injection of Insulin icodec for 26 weeks, using PDS290 prefilled pen-injector in combination with insulin aspart at a starting dose of 7 times the pre-trial total daily basal insulin dose + 50% of their 7 times total daily basal insulin dose. 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: lesser than (\<) 4.4 millimoles per liter (mmol/L): dose reduced by 20 units (U); 4.4-7.2 mmol/L: no adjustment; greater than (\>) 7.2 mmol/L: dose increased by 20 U. Dose titration of insulin aspart was based on the respective premeal(s) and bedtime SMPG measured.	Insulin Glargine n=291 Participants Participants were to receive once daily s.c. injection of Insulin glargine for 26 weeks, using SoloSTAR pre-filled pen-injector in combination with insulin aspart. Participants were to perform 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 mmol/L: dose reduced by 3 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.
Number of Severe Hypoglycaemic Episodes (Level 3)	7 Episodes	3 Episodes

SECONDARY outcome

Timeframe: From baseline (week 0) to week 31

Population: Safety analysis set included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.

Clinically significant hypoglycaemic episodes (level 2) were defined as episodes that were sufficiently low to indicate serious, clinically important hypoglycaemia with plasma glucose value of less than (\<) 3.0 mmol/L (54 mg/dL). The outcome data was evaluated based on the on-treatment observation period. The on-treatment observation 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 of trial visit, 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.

Outcome measures

Outcome measures
Measure	Insulin Icodec n=291 Participants Participants were to receive once weekly subcutaneous (s.c.) injection of Insulin icodec for 26 weeks, using PDS290 prefilled pen-injector in combination with insulin aspart at a starting dose of 7 times the pre-trial total daily basal insulin dose + 50% of their 7 times total daily basal insulin dose. 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: lesser than (\<) 4.4 millimoles per liter (mmol/L): dose reduced by 20 units (U); 4.4-7.2 mmol/L: no adjustment; greater than (\>) 7.2 mmol/L: dose increased by 20 U. Dose titration of insulin aspart was based on the respective premeal(s) and bedtime SMPG measured.	Insulin Glargine n=291 Participants Participants were to receive once daily s.c. injection of Insulin glargine for 26 weeks, using SoloSTAR pre-filled pen-injector in combination with insulin aspart. Participants were to perform 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 mmol/L: dose reduced by 3 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.
Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (<3.0 mmol/L (54 mg/dL) Confirmed by Blood Glucose (BG) Meter)	937 Episodes	935 Episodes

SECONDARY outcome

Timeframe: From baseline (week 0) to week 31

Population: Safety analysis set included all participants randomly assigned to trial treatment and who took at least 1 dose of trial product.

Clinically significant hypoglycaemic episodes (level 2) were defined as episodes that were sufficiently low to indicate serious, clinically important hypoglycaemia with plasma glucose value of less than (\<) 3.0 mmol/L (54 mg/dL). Severe hypoglycaemic episodes (level 3) were defined as episodes that were associated with severe cognitive impairment requiring external assistance for recovery. The outcome data was evaluated based on the in-trial observation period. The on-treatment observation 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 of trial visit, 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.

Outcome measures

Outcome measures
Measure	Insulin Icodec n=291 Participants Participants were to receive once weekly subcutaneous (s.c.) injection of Insulin icodec for 26 weeks, using PDS290 prefilled pen-injector in combination with insulin aspart at a starting dose of 7 times the pre-trial total daily basal insulin dose + 50% of their 7 times total daily basal insulin dose. 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: lesser than (\<) 4.4 millimoles per liter (mmol/L): dose reduced by 20 units (U); 4.4-7.2 mmol/L: no adjustment; greater than (\>) 7.2 mmol/L: dose increased by 20 U. Dose titration of insulin aspart was based on the respective premeal(s) and bedtime SMPG measured.	Insulin Glargine n=291 Participants Participants were to receive once daily s.c. injection of Insulin glargine for 26 weeks, using SoloSTAR pre-filled pen-injector in combination with insulin aspart. Participants were to perform 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 mmol/L: dose reduced by 3 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.
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)	944 Episodes	938 Episodes

SECONDARY outcome

Timeframe: From week 22 to week 26

Population: Full analysis set included all randomised participants. Overall number of participants analyzed = participants with available data for this outcome measure.

Percentage of time spent less than (\<) 3.0 mmol/L (54 mg/dL) using CGM system from week 22 to week 26 is presented. The outcome data was evaluated based on the in-trial observation 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) and death for participants who died before any of the above.

Outcome measures

Outcome measures
Measure	Insulin Icodec n=244 Participants Participants were to receive once weekly subcutaneous (s.c.) injection of Insulin icodec for 26 weeks, using PDS290 prefilled pen-injector in combination with insulin aspart at a starting dose of 7 times the pre-trial total daily basal insulin dose + 50% of their 7 times total daily basal insulin dose. 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: lesser than (\<) 4.4 millimoles per liter (mmol/L): dose reduced by 20 units (U); 4.4-7.2 mmol/L: no adjustment; greater than (\>) 7.2 mmol/L: dose increased by 20 U. Dose titration of insulin aspart was based on the respective premeal(s) and bedtime SMPG measured.	Insulin Glargine n=237 Participants Participants were to receive once daily s.c. injection of Insulin glargine for 26 weeks, using SoloSTAR pre-filled pen-injector in combination with insulin aspart. Participants were to perform 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 mmol/L: dose reduced by 3 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.
Percentage of Time Spent Below 3.0 mmol/L (54 mg/dL) Using Continuous Glucose Monitoring (CGM) System	0.73 Percentage (%) of time Standard Deviation 1.14	0.61 Percentage (%) of time Standard Deviation 1.07

SECONDARY outcome

Timeframe: From week 22 to week 26

Population: Full analysis set included all randomised participants. Overall number of participants analyzed = participants with available data for this outcome measure.

Percentage of time spent \> 10 mmol/L (180 mg/dL) using CGM system from week 22 to week 26 is presented. The outcome data was evaluated based on the in-trial observation 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) and death for participants who died before any of the above.

Outcome measures

Outcome measures
Measure	Insulin Icodec n=244 Participants Participants were to receive once weekly subcutaneous (s.c.) injection of Insulin icodec for 26 weeks, using PDS290 prefilled pen-injector in combination with insulin aspart at a starting dose of 7 times the pre-trial total daily basal insulin dose + 50% of their 7 times total daily basal insulin dose. 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: lesser than (\<) 4.4 millimoles per liter (mmol/L): dose reduced by 20 units (U); 4.4-7.2 mmol/L: no adjustment; greater than (\>) 7.2 mmol/L: dose increased by 20 U. Dose titration of insulin aspart was based on the respective premeal(s) and bedtime SMPG measured.	Insulin Glargine n=237 Participants Participants were to receive once daily s.c. injection of Insulin glargine for 26 weeks, using SoloSTAR pre-filled pen-injector in combination with insulin aspart. Participants were to perform 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 mmol/L: dose reduced by 3 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.
Percentage of Time Spent Above 10 mmol/L (180 mg/dL) Using Continuous Glucose Monitoring (CGM) System	30.47 Percentage (%) of time Standard Deviation 15.90	31.30 Percentage (%) of time Standard Deviation 16.67

SECONDARY outcome

Timeframe: From week 24 to week 26

Population: Full analysis set included all randomised participants. Overall number of participants analyzed = participants with available data for this outcome measure.

Estimated mean weekly insulin dose during the last 2 weeks of treatment (from week 24 to week 26) is presented. The outcome data was evaluated based on the on-treatment observation period. The on-treatment observation 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 of trial visit, 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.

Outcome measures

Outcome measures
Measure	Insulin Icodec n=273 Participants Participants were to receive once weekly subcutaneous (s.c.) injection of Insulin icodec for 26 weeks, using PDS290 prefilled pen-injector in combination with insulin aspart at a starting dose of 7 times the pre-trial total daily basal insulin dose + 50% of their 7 times total daily basal insulin dose. 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: lesser than (\<) 4.4 millimoles per liter (mmol/L): dose reduced by 20 units (U); 4.4-7.2 mmol/L: no adjustment; greater than (\>) 7.2 mmol/L: dose increased by 20 U. Dose titration of insulin aspart was based on the respective premeal(s) and bedtime SMPG measured.	Insulin Glargine n=266 Participants Participants were to receive once daily s.c. injection of Insulin glargine for 26 weeks, using SoloSTAR pre-filled pen-injector in combination with insulin aspart. Participants were to perform 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 mmol/L: dose reduced by 3 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.
Mean Weekly Insulin Dose	513.54 Units of insulin Interval 486.1 to 542.52	559.05 Units of insulin Interval 528.63 to 591.22

SECONDARY outcome

Timeframe: Baseline (week 0), Week 26

Population: Full analysis set included all randomised participants.

Change in body weight from baseline (week 0) to week 26 is presented. The outcome data was evaluated based on the in-trial observation 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) and death for participants who died before any of the above.

Outcome measures

Outcome measures
Measure	Insulin Icodec n=291 Participants Participants were to receive once weekly subcutaneous (s.c.) injection of Insulin icodec for 26 weeks, using PDS290 prefilled pen-injector in combination with insulin aspart at a starting dose of 7 times the pre-trial total daily basal insulin dose + 50% of their 7 times total daily basal insulin dose. 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: lesser than (\<) 4.4 millimoles per liter (mmol/L): dose reduced by 20 units (U); 4.4-7.2 mmol/L: no adjustment; greater than (\>) 7.2 mmol/L: dose increased by 20 U. Dose titration of insulin aspart was based on the respective premeal(s) and bedtime SMPG measured.	Insulin Glargine n=291 Participants Participants were to receive once daily s.c. injection of Insulin glargine for 26 weeks, using SoloSTAR pre-filled pen-injector in combination with insulin aspart. Participants were to perform 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 mmol/L: dose reduced by 3 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.
Change in Body Weight	2.73 Kilograms (kg) Standard Error 0.29	2.16 Kilograms (kg) Standard Error 0.40

Adverse Events

Insulin Icodec

Serious events: 22 serious events

Other events: 48 other events

Deaths: 2 deaths

Insulin Glargine

Serious events: 25 serious events

Other events: 44 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Insulin Icodec n=291 participants at risk Participants were to receive once weekly subcutaneous (s.c.) injection of Insulin icodec for 26 weeks, using PDS290 prefilled pen-injector in combination with insulin aspart at a starting dose of 7 times the pre-trial total daily basal insulin dose + 50% of their 7 times total daily basal insulin dose. 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: lesser than (\<) 4.4 millimoles per liter (mmol/L): dose reduced by 20 units (U); 4.4-7.2 mmol/L: no adjustment; greater than (\>) 7.2 mmol/L: dose increased by 20 U. Dose titration of insulin aspart was based on the respective premeal(s) and bedtime SMPG measured.	Insulin Glargine n=291 participants at risk Participants were to receive once daily s.c. injection of Insulin glargine for 26 weeks, using SoloSTAR pre-filled pen-injector in combination with insulin aspart. Participants were to perform 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 mmol/L: dose reduced by 3 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.
Infections and infestations COVID-19	8.6% 25/291 • Number of events 25 • From baseline (week 0) to week 31. All presented AEs are treatment emergent. Treatment emergent adverse events (TEAEs): events that had onset date during on-treatment period, time period in which participants was considered exposed to trial product. Safety analysis set included all randomised participants randomly assigned to trial treatment who took at least 1 dose of trial product.	7.6% 22/291 • Number of events 24 • From baseline (week 0) to week 31. All presented AEs are treatment emergent. Treatment emergent adverse events (TEAEs): events that had onset date during on-treatment period, time period in which participants was considered exposed to trial product. Safety analysis set included all randomised participants randomly assigned to trial treatment who took at least 1 dose of trial product.
Eye disorders Diabetic retinopathy	4.1% 12/291 • Number of events 14 • From baseline (week 0) to week 31. All presented AEs are treatment emergent. Treatment emergent adverse events (TEAEs): events that had onset date during on-treatment period, time period in which participants was considered exposed to trial product. Safety analysis set included all randomised participants randomly assigned to trial treatment who took at least 1 dose of trial product.	5.2% 15/291 • Number of events 15 • From baseline (week 0) to week 31. All presented AEs are treatment emergent. Treatment emergent adverse events (TEAEs): events that had onset date during on-treatment period, time period in which participants was considered exposed to trial product. Safety analysis set included all randomised participants randomly assigned to trial treatment who took at least 1 dose of trial product.
Gastrointestinal disorders Diarrhoea	5.2% 15/291 • Number of events 18 • From baseline (week 0) to week 31. All presented AEs are treatment emergent. Treatment emergent adverse events (TEAEs): events that had onset date during on-treatment period, time period in which participants was considered exposed to trial product. Safety analysis set included all randomised participants randomly assigned to trial treatment who took at least 1 dose of trial product.	3.1% 9/291 • Number of events 9 • From baseline (week 0) to week 31. All presented AEs are treatment emergent. Treatment emergent adverse events (TEAEs): events that had onset date during on-treatment period, time period in which participants was considered exposed to trial product. Safety analysis set included all randomised participants randomly assigned to trial treatment who took at least 1 dose of trial product.

Additional Information

Clinical Reporting Office (2834)

Novo Nordisk A/S

Phone: (+1) 866-867-7178

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee At the end of the trial, one or more scientific publications may be prepared collaboratively by the investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for up to 60 days to protect intellectual property.
Publication restrictions are in place

Restriction type: OTHER