Trial Outcomes & Findings for Research Study Comparing a New Medicine "Fast-acting Insulin Aspart" to Another Already Available Medicine "NovoRapid"/"NovoLog" in People With Type 2 Diabetes (NCT NCT03268005)

NCT ID: NCT03268005

Last Updated: 2022-01-11

Results Overview

Change from baseline (week 0) in glycosylated haemoglobin (HbA1c) was evaluated at week 16. The endpoint was evaluated based on data from the in-trial observation period. In-trial observation period was from date of randomisation and until last trial-related participant-site contact.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 1264 participants
• Primary outcome timeframe: Week 0, week 16
• Results posted on: 2022-01-11

Participant Flow

The trial was conducted at 165 sites in 17 countries as follows: Argentina-3, Bulgaria-4, Canada-10, Croatia-4, Czech Republic-4, Germany-6, Greece-8, Italy-4, Poland-10, Republic of Korea-6, Romania-6, Russia-8, Serbia-9, Slovakia-5, Spain-8, Ukraine-6 and United States (US)-62. Two sites in the US screened but didn't randomise any subject.

There was a 12-week run-in period primarily for optimisation of the basal insulin and reinforcement of subject training in trial procedures, diabetes education and dietary training. Out of the 1264 participants enrolled in the study, 173 were run-in failures and 1091 were randomised.

Participant milestones

Measure	Faster Aspart Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid Participants received insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Overall Study STARTED	546	545
Overall Study Full Analysis Set	546	545
Overall Study Safety Analysis Set	544	544
Overall Study COMPLETED	531	531
Overall Study NOT COMPLETED	15	14

Reasons for withdrawal

Measure	Faster Aspart Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid Participants received insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Overall Study Death	2	1
Overall Study Lost to Follow-up	2	2
Overall Study Withdrawal by Subject	11	11

Baseline Characteristics

Research Study Comparing a New Medicine "Fast-acting Insulin Aspart" to Another Already Available Medicine "NovoRapid"/"NovoLog" in People With Type 2 Diabetes

Baseline characteristics by cohort

Measure	Faster Aspart n=546 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=545 Participants Participants received insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	Total n=1091 Participants Total of all reporting groups
Age, Continuous	62.6 Years STANDARD_DEVIATION 8.6 • n=5 Participants	62.1 Years STANDARD_DEVIATION 8.8 • n=7 Participants	62.3 Years STANDARD_DEVIATION 8.7 • n=5 Participants
Sex: Female, Male Female	281 Participants n=5 Participants	256 Participants n=7 Participants	537 Participants n=5 Participants
Sex: Female, Male Male	265 Participants n=5 Participants	289 Participants n=7 Participants	554 Participants n=5 Participants
Race/Ethnicity, Customized White	487 Participants n=5 Participants	487 Participants n=7 Participants	974 Participants n=5 Participants
Race/Ethnicity, Customized Asian	43 Participants n=5 Participants	31 Participants n=7 Participants	74 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	14 Participants n=5 Participants	19 Participants n=7 Participants	33 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	485 Participants n=5 Participants	488 Participants n=7 Participants	973 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic Latino	61 Participants n=5 Participants	57 Participants n=7 Participants	118 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 0, week 16

Population: Overall number of participants analyzed = number of participants with available data.

Change from baseline (week 0) in glycosylated haemoglobin (HbA1c) was evaluated at week 16. The endpoint was evaluated based on data from the in-trial observation period. In-trial observation period was from date of randomisation and until last trial-related participant-site contact.

Outcome measures

Measure	Faster Aspart n=544 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=539 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Change in Glycosylated Haemoglobin (HbA1c)	-0.15 Percentage of HbA1c Standard Deviation 0.62	-0.09 Percentage of HbA1c Standard Deviation 0.60

SECONDARY outcome

Timeframe: Week 0, week 16

Population: Overall number of participants analyzed = number of participants with available data.

Change from baseline (week 0) in 1-hour postprandial glucose (PPG) increment was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.

Outcome measures

Measure	Faster Aspart n=519 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=523 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Change From Baseline in 1-hour PPG Increment	-0.43 mmol/L Standard Deviation 2.45	0.08 mmol/L Standard Deviation 2.65

SECONDARY outcome

Timeframe: Week 0, week 16

Population: Overall number of participants analyzed = number of participants with available data.

Change from baseline (week 0) in 1,5-anhydroglucitol was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.

Outcome measures

Measure	Faster Aspart n=534 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=531 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Change From Baseline in 1,5-anhydroglucitol	1.38 mmol/L Standard Deviation 3.10	0.89 mmol/L Standard Deviation 3.31

SECONDARY outcome

Timeframe: Week 0, week 16

Population: Overall number of participants analyzed = number of participants with available data.

Change from baseline (week 0) in fasting plasma glucose was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.

Outcome measures

Measure	Faster Aspart n=533 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=530 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Change From Baseline in Fasting Plasma Glucose (FPG)	0.56 mmol/L Standard Deviation 2.38	0.68 mmol/L Standard Deviation 2.40

SECONDARY outcome

Timeframe: 16 weeks after randomisation

Population: Overall number of participants analyzed = full analysis set (FAS) which comprised all randomised participants. Number Analyzed = number of participants with available data.

Number of participants reaching HbA1c <7.0% (53 mmol/L) was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.

Outcome measures

Measure	Faster Aspart n=546 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=545 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Participants Who Achieved HbA1c <7.0% (53 mmol/L) (Yes/No) Yes	271 Participants	282 Participants
Participants Who Achieved HbA1c <7.0% (53 mmol/L) (Yes/No) No	275 Participants	263 Participants

SECONDARY outcome

Timeframe: 16 weeks after randomisation

Population: Overall number of participants analyzed = full analysis set (FAS) which comprised all randomised participants. Number Analyzed = number of participants with available data.

Number of participants reaching HbA1c <7.0% (53 mmol/L) without severe hypoglycaemia episodes was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.

Outcome measures

Measure	Faster Aspart n=546 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=545 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Participants Who Achieved HbA1c <7.0% (53 mmol/L) Without Severe Hypoglycaemia Episodes (Yes/No) Yes	265 Participants	278 Participants
Participants Who Achieved HbA1c <7.0% (53 mmol/L) Without Severe Hypoglycaemia Episodes (Yes/No) No	281 Participants	267 Participants

SECONDARY outcome

Timeframe: Week 0, week 16

Population: Overall number of participants analyzed = full analysis set (FAS) which comprised all randomised participants. Number Analyzed = number of participants with available data.

Change from baseline (week 0) in 30-minute, 1-hour, 2-hour, 3-hour and 4-hour postprandial glucose (PPG [meal test]) was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact. Meal test: The subjects were given a carbohydrate-rich standardised liquid meal immediately after bolus (faster aspart or NovoRapid) infusion in the morning of the meal test. The subjects were to consume the meal as quickly as possible (within 12 minutes) and blood samples were drawn after 30 minutes, 1, 2, 3 and 4 hours from the start of the meal.

Outcome measures

Measure	Faster Aspart n=546 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=545 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Change From Baseline (Week 0) in 30-minute, 1-hour, 2-hour, 3-hour and 4-hour Postprandial Glucose (PPG [Meal Test]) 30-min	0.31 mmol/L Standard Deviation 2.90	0.55 mmol/L Standard Deviation 2.80
Change From Baseline (Week 0) in 30-minute, 1-hour, 2-hour, 3-hour and 4-hour Postprandial Glucose (PPG [Meal Test]) 1-hour	0.03 mmol/L Standard Deviation 3.30	0.68 mmol/L Standard Deviation 3.23
Change From Baseline (Week 0) in 30-minute, 1-hour, 2-hour, 3-hour and 4-hour Postprandial Glucose (PPG [Meal Test]) 2-hour	0.08 mmol/L Standard Deviation 3.96	0.61 mmol/L Standard Deviation 3.48
Change From Baseline (Week 0) in 30-minute, 1-hour, 2-hour, 3-hour and 4-hour Postprandial Glucose (PPG [Meal Test]) 3-hour	0.30 mmol/L Standard Deviation 3.85	0.89 mmol/L Standard Deviation 3.72
Change From Baseline (Week 0) in 30-minute, 1-hour, 2-hour, 3-hour and 4-hour Postprandial Glucose (PPG [Meal Test]) 4-hour	0.51 mmol/L Standard Deviation 3.47	0.75 mmol/L Standard Deviation 3.51

SECONDARY outcome

Timeframe: Week 0, week 16

Population: Overall number of participants analyzed = full analysis set (FAS) which comprised all randomised participants. Number Analyzed = number of participants with available data.

Change from baseline (week 0) in 30-minute, 1-hour, 2-hour, 3-hour and 4-hour PPG increment (meal test) was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact. Meal test: The subjects were given a carbohydrate-rich standardised liquid meal immediately after bolus (faster aspart or NovoRapid) infusion in the morning of the meal test. The subjects were to consume the meal as quickly as possible (within 12 minutes) and blood samples were drawn after 30 minutes, 1, 2, 3 and 4 hours from the start of the meal. PPG incremental value for each time point was derived as PPG value at that time point minus the preprandial glucose value.

Outcome measures

Measure	Faster Aspart n=546 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=545 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Change From Baseline (Week 0) in 30-minute, 1-hour, 2-hour, 3-hour and 4-hour PPG Increment (Meal Test) 30-min	-0.13 mmol/L Standard Deviation 1.85	-0.05 mmol/L Standard Deviation 1.95
Change From Baseline (Week 0) in 30-minute, 1-hour, 2-hour, 3-hour and 4-hour PPG Increment (Meal Test) 1-hour	-0.43 mmol/L Standard Deviation 2.45	0.08 mmol/L Standard Deviation 2.65
Change From Baseline (Week 0) in 30-minute, 1-hour, 2-hour, 3-hour and 4-hour PPG Increment (Meal Test) 2-hour	-0.37 mmol/L Standard Deviation 3.25	0.001 mmol/L Standard Deviation 3.13
Change From Baseline (Week 0) in 30-minute, 1-hour, 2-hour, 3-hour and 4-hour PPG Increment (Meal Test) 3-hour	-0.15 mmol/L Standard Deviation 3.23	0.28 mmol/L Standard Deviation 3.54
Change From Baseline (Week 0) in 30-minute, 1-hour, 2-hour, 3-hour and 4-hour PPG Increment (Meal Test) 4-hour	0.04 mmol/L Standard Deviation 3.00	0.15 mmol/L Standard Deviation 3.45

SECONDARY outcome

Timeframe: Week 0, week 16

Population: Overall number of participants analyzed = number of participants with available data.

Change from baseline (week 0) in mean of the 7-9-7 point SMPG profile was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. 7-9-7 point SMPG was measured at the following mentioned time points: 1) Before breakfast, 2) 60 mins after the start of Breakfast, 3) Before lunch, 4) 60 mins after the start of lunch, 5) Before main evening meal, 6) 60 mins after the start of main evening meal, 7) At bedtime, 8) At 4 AM, 9) Before breakfast.

Outcome measures

Measure	Faster Aspart n=454 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=464 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Change From Baseline in Mean of the 7-9-7 Point Self-measured Plasma Glucose (SMPG) Profile	-0.56 mmol/L Standard Deviation 1.66	-0.50 mmol/L Standard Deviation 1.61

SECONDARY outcome

Timeframe: Week 0, week 16

Population: Overall number of participants analyzed = full analysis set (FAS) which comprised all randomised participants. Number Analyzed = number of participants with available data.

Change from baseline (week 0) in PPG (breakfast, lunch, main evening meal and mean over all meals) of the 7-9-7 point SMPG profile was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.

Outcome measures

Measure	Faster Aspart n=546 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=545 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Change From Baseline of the 7-9-7 Point SMPG Profile: PPG (Mean, Breakfast, Lunch and Main Evening Meal) Lunch	-0.78 mmol/L Standard Deviation 2.48	-0.58 mmol/L Standard Deviation 2.68
Change From Baseline of the 7-9-7 Point SMPG Profile: PPG (Mean, Breakfast, Lunch and Main Evening Meal) All meals	-0.75 mmol/L Standard Deviation 1.89	-0.52 mmol/L Standard Deviation 1.91
Change From Baseline of the 7-9-7 Point SMPG Profile: PPG (Mean, Breakfast, Lunch and Main Evening Meal) Breakfast	-0.38 mmol/L Standard Deviation 2.53	-0.28 mmol/L Standard Deviation 2.44
Change From Baseline of the 7-9-7 Point SMPG Profile: PPG (Mean, Breakfast, Lunch and Main Evening Meal) Main evening meal	-1.04 mmol/L Standard Deviation 2.67	-0.71 mmol/L Standard Deviation 2.50

SECONDARY outcome

Timeframe: Week 0, week 16

Population: Overall number of participants analyzed = full analysis set (FAS) which comprised all randomised participants. Number Analyzed = number of participants with available data.

Change from baseline (week 0) in PPG increment (breakfast, lunch, main evening meal and mean over all meals) of the 7-9-7 point SMPG profile was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. PPG increment based on the 7-9-7-point profiles were derived separately for PG measurements made at 1 hour after main meals (breakfast, lunch and main evening meal). PPG incremental value for each time point was derived as PPG value at that time point minus the preprandial glucose value. In trial observation period was from date of randomisation and until last trial-related participant-site contact.

Outcome measures

Measure	Faster Aspart n=546 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=545 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Change From Baseline of the 7-9-7 Point SMPG Profile: PPG Increment (Mean, Breakfast, Lunch and Main Evening Meal) Breakfast	-0.56 mmol/L Standard Deviation 2.23	-0.42 mmol/L Standard Deviation 2.17
Change From Baseline of the 7-9-7 Point SMPG Profile: PPG Increment (Mean, Breakfast, Lunch and Main Evening Meal) Lunch	-0.38 mmol/L Standard Deviation 2.69	-0.23 mmol/L Standard Deviation 2.46
Change From Baseline of the 7-9-7 Point SMPG Profile: PPG Increment (Mean, Breakfast, Lunch and Main Evening Meal) Main evening meal	-0.44 mmol/L Standard Deviation 2.61	-0.10 mmol/L Standard Deviation 2.28
Change From Baseline of the 7-9-7 Point SMPG Profile: PPG Increment (Mean, Breakfast, Lunch and Main Evening Meal) All meals	-0.48 mmol/L Standard Deviation 1.55	-0.23 mmol/L Standard Deviation 1.42

SECONDARY outcome

Timeframe: Week 0, week 16

Population: Overall number of participants analyzed = number of participants with available data.

Fluctuation in 7-point SMPG profile was the average absolute difference from the mean of the SMPG profile. Reported results are fluctuation in the 7-9-7 point SMPG profile from baseline (week 0) after 16 weeks of randomisation (i.e., week 16). The results are presented as ratio to baseline. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.

Outcome measures

Measure	Faster Aspart n=454 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=464 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Change From Baseline of the 7-9-7 Point SMPG Profile: Fluctuation in 7-9-7 Point Profile	0.82 Ratio Geometric Coefficient of Variation 48.32	0.85 Ratio Geometric Coefficient of Variation 55.06

SECONDARY outcome

Timeframe: Week 0, week 16

Population: Overall number of participants analyzed = full analysis set (FAS) which comprised all randomised participants. Number Analyzed = number of participants with available data.

Change from baseline (week 0) in nocturnal SMPG measurements was assessed by considering the differences between PG values available at bedtime, at 4 AM and the before breakfast value the following day: (4 AM PG value minus at bedtime PG value), (before breakfast PG value minus at bedtime PG value) and (before breakfast PG value minus 4 AM PG value). Change from baseline in nocturnal increments in SMPG measurements of the 7-9-7 point SMPG profile was evaluated after 16 weeks of randomisation and presented during three different time intervals as follows: 1) 04:00 to breakfast, 2) bedtime to 04:00, and 3) bedtime to breakfast. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.

Outcome measures

Measure	Faster Aspart n=546 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=545 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Change From Baseline of the 7-9-7 Point SMPG Profile: Nocturnal SMPG Measurements Bedtime to breakfast	1.30 mmol/L Standard Deviation 4.25	0.90 mmol/L Standard Deviation 3.99
Change From Baseline of the 7-9-7 Point SMPG Profile: Nocturnal SMPG Measurements Bedtime to 04:00	0.70 mmol/L Standard Deviation 4.09	0.29 mmol/L Standard Deviation 4.09
Change From Baseline of the 7-9-7 Point SMPG Profile: Nocturnal SMPG Measurements 04:00 to breakfast	0.66 mmol/L Standard Deviation 2.76	0.75 mmol/L Standard Deviation 2.87

SECONDARY outcome

Timeframe: 16 weeks after randomisation

Population: Overall number of participants analyzed = full analysis set (FAS) which comprised all randomised participants. Number Analyzed = number of participants with available data.

Participants reaching overall PPG (1 hour) ≤7.8 mmol/L [140 mg/dL] was evaluated after 16 weeks of randomisation. Participants without a postprandial glucose measurement at week 16 were considered not to have achieved HbA1c target at week 16. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.

Outcome measures

Measure	Faster Aspart n=546 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=545 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Participants Who Achieved Overall PPG (1 Hour) <7.8 mmol/L (140 mg/dL) (Yes/No) No	360 Participants	353 Participants
Participants Who Achieved Overall PPG (1 Hour) <7.8 mmol/L (140 mg/dL) (Yes/No) Yes	186 Participants	192 Participants

SECONDARY outcome

Timeframe: 16 weeks after randomisation

Population: Overall number of participants analyzed = full analysis set (FAS) which comprised all randomised participants. Number Analyzed = number of participants with available data.

Participants reaching overall PPG (1 hour) ≤7.8 mmol/L [140 mg/dL] without severe hypoglycaemia episodes was evaluated after 16 weeks of randomisation. Participants without a postprandial glucose measurement at week 16 were considered not to have achieved HbA1c target at week 16. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.

Outcome measures

Measure	Faster Aspart n=546 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=545 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Participants Who Achieved Overall PPG <7.8 mmol/L (140 mg/dL) Without Severe Hypoglycaemia Episodes (Yes/No) Yes	182 Participants	190 Participants
Participants Who Achieved Overall PPG <7.8 mmol/L (140 mg/dL) Without Severe Hypoglycaemia Episodes (Yes/No) No	364 Participants	355 Participants

SECONDARY outcome

Timeframe: 16 weeks from randomisation

Population: Overall number of participants analyzed = number of participants with available data.

Total bolus insulin dose (Units/day) was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

Outcome measures

Measure	Faster Aspart n=544 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=542 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Total Bolus Insulin Dose: in Units/Day	54.72 Units/day Standard Deviation 35.82	53.38 Units/day Standard Deviation 35.35

SECONDARY outcome

Timeframe: 16 weeks from randomisation

Population: Overall number of participants analyzed = number of participants with available data.

Total bolus insulin dose (Units/kg/day) was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

Outcome measures

Measure	Faster Aspart n=544 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=542 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Total Bolus Insulin Dose: in Units/kg/Day	0.57 Units/kg/day Standard Deviation 0.33	0.55 Units/kg/day Standard Deviation 0.34

SECONDARY outcome

Timeframe: 16 weeks from randomisation

Population: Overall number of participants analyzed = number of participants with available data.

Total basal insulin dose (Units/day) was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

Outcome measures

Measure	Faster Aspart n=544 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=542 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Total Basal Insulin Dose: in Units/Day	63.76 Units/day Standard Deviation 35.21	62.25 Units/day Standard Deviation 36.03

SECONDARY outcome

Timeframe: 16 weeks from randomisation

Population: Overall number of participants analyzed = number of participants with available data.

Total basal insulin dose (Units/kg/day) was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

Outcome measures

Measure	Faster Aspart n=544 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=542 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Total Basal Insulin Dose: in Units/kg/Day	0.66 Units/kg/day Standard Deviation 0.32	0.64 Units/kg/day Standard Deviation 0.32

SECONDARY outcome

Timeframe: 16 weeks from randomisation

Population: Overall number of participants analyzed = safety analysis set (SAS) which comprised all randomised participants. Number Analyzed = number of participants with available data.

Individual meal time bolus insulin dose (Units) for breakast, lunch and main evening meal was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

Outcome measures

Measure	Faster Aspart n=544 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=544 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Individual Meal Insulin Dose: in Units Daily main evening meal	19.88 Units Standard Deviation 13.46	19.85 Units Standard Deviation 14.47
Individual Meal Insulin Dose: in Units Breakfast	16.27 Units Standard Deviation 12.04	15.52 Units Standard Deviation 11.38
Individual Meal Insulin Dose: in Units Lunch	18.51 Units Standard Deviation 12.09	17.96 Units Standard Deviation 11.73

SECONDARY outcome

Timeframe: 16 weeks from randomisation

Population: Overall number of participants analyzed = safety analysis set (SAS) which comprised all randomised participants. Number Analyzed = number of participants with available data.

Individual meal time bolus insulin dose (Units/kg) for breakast, lunch and main evening meal was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

Outcome measures

Measure	Faster Aspart n=544 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=544 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Individual Meal Insulin Dose: in Units/kg Breakfast	0.17 Units/kg Standard Deviation 0.12	0.16 Units/kg Standard Deviation 0.11
Individual Meal Insulin Dose: in Units/kg Lunch	0.19 Units/kg Standard Deviation 0.11	0.19 Units/kg Standard Deviation 0.12
Individual Meal Insulin Dose: in Units/kg Daily main evening meal	0.21 Units/kg Standard Deviation 0.13	0.20 Units/kg Standard Deviation 0.14

SECONDARY outcome

Timeframe: Week 0, week 16

Population: Overall number of participants analyzed = full analysis set (FAS) which comprised all randomised participants. Number Analyzed = number of participants with available data.

Reported results are lipids-lipoproteins (total cholesterol, high density lipoproteins, low density lipoproteins) values are given as ratio to baseline (week 0) after 16 weeks. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.

Outcome measures

Measure	Faster Aspart n=546 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=545 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Change From Baseline in Lipids-lipoproteins Profile (Total Cholesterol, High Density Lipoproteins, Low Density Lipoproteins) - Ratio to Baseline Total cholesterol	1.01 Ratio Geometric Coefficient of Variation 15.98	1.00 Ratio Geometric Coefficient of Variation 17.09
Change From Baseline in Lipids-lipoproteins Profile (Total Cholesterol, High Density Lipoproteins, Low Density Lipoproteins) - Ratio to Baseline High density lipoproteins	0.97 Ratio Geometric Coefficient of Variation 14.47	0.98 Ratio Geometric Coefficient of Variation 17.57
Change From Baseline in Lipids-lipoproteins Profile (Total Cholesterol, High Density Lipoproteins, Low Density Lipoproteins) - Ratio to Baseline Low density lipoproteins	0.99 Ratio Geometric Coefficient of Variation 25.36	0.99 Ratio Geometric Coefficient of Variation 40.51

SECONDARY outcome

Timeframe: Weeks 0-16

Population: Overall number of participants analyzed = number of participants with available data.

Number of treatment emergent adverse events were recorded from week 0 to week 16. The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

Outcome measures

Measure	Faster Aspart n=544 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=544 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Number of Treatment Emergent Adverse Events	667 Events	643 Events

SECONDARY outcome

Timeframe: Weeks 0-16

Population: Overall number of participants analyzed = number of participants with available data.

Number of treatment emergent injection site reactions were recorded from week 0 to week 16. The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

Outcome measures

Measure	Faster Aspart n=544 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=544 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Number of Treatment Emergent Injection Site Reactions	3 Number of injection site reactions	1 Number of injection site reactions

SECONDARY outcome

Timeframe: Weeks 0-16

Population: Overall number of participants analyzed = safety analysis set (SAS) which comprised all randomised participants. Number Analyzed = number of participants with available data.

ADA classification of hypos:

1. Severe: Requiring assistance of another person to actively administer carbohydrate/glucagon/take other corrective actions. PG levels may not be available during an event, but neurological recovery following return of PG to normal is considered sufficient evidence that event was induced by a low PG level.

2. Documented symptomatic: PG ≤3.9 mmol/L with symptoms.

3. Asymptomatic: PG ≤3.9 mmol/L without symptoms.

4. Probable symptomatic: No measurement with symptoms.

5. Pseudo: PG >3.9 mmol/L with symptoms.

6. Unclassifiable.

NN classification of hypos:

1. BG confirmed: PG <3.1 mmol/L with/without symptoms.

2. Severe or BG confirmed symptomatic: Severe as per ADA and BG confirmed by PG <3.1 mmol/L with symptoms.

3. Severe or BG confirmed: Severe as per ADA and BG confirmed by PG <3.1 mmol/L with/without symptoms.

4. Unclassifiable. Not able to self treat-unclassifiable: Not able to self treat but not classifiable as severe hypoglycaemia.

Outcome measures

Measure	Faster Aspart n=544 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=544 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Number of Treatment Emergent Hypoglycaemic Episodes (Hypos) According to the American Diabetes Association (ADA) and Novo Nordisk (NN) Definition: Overall ADA: Probable symptomatic	68 Number of hypoglycaemic episodes	68 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes (Hypos) According to the American Diabetes Association (ADA) and Novo Nordisk (NN) Definition: Overall Not able to selftreat - unclassifiable	0 Number of hypoglycaemic episodes	0 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes (Hypos) According to the American Diabetes Association (ADA) and Novo Nordisk (NN) Definition: Overall ADA: Severe	18 Number of hypoglycaemic episodes	14 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes (Hypos) According to the American Diabetes Association (ADA) and Novo Nordisk (NN) Definition: Overall ADA: Documented symptomatic	5038 Number of hypoglycaemic episodes	6165 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes (Hypos) According to the American Diabetes Association (ADA) and Novo Nordisk (NN) Definition: Overall ADA: Asymptomatic	3761 Number of hypoglycaemic episodes	3681 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes (Hypos) According to the American Diabetes Association (ADA) and Novo Nordisk (NN) Definition: Overall ADA: Pseudo	145 Number of hypoglycaemic episodes	75 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes (Hypos) According to the American Diabetes Association (ADA) and Novo Nordisk (NN) Definition: Overall ADA: Unclassifiable	3 Number of hypoglycaemic episodes	3 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes (Hypos) According to the American Diabetes Association (ADA) and Novo Nordisk (NN) Definition: Overall NN: BG confirmed	2209 Number of hypoglycaemic episodes	2735 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes (Hypos) According to the American Diabetes Association (ADA) and Novo Nordisk (NN) Definition: Overall NN: Severe or BG confirmed symptomatic	1490 Number of hypoglycaemic episodes	2055 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes (Hypos) According to the American Diabetes Association (ADA) and Novo Nordisk (NN) Definition: Overall NN: Severe or BG confirmed	2227 Number of hypoglycaemic episodes	2749 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes (Hypos) According to the American Diabetes Association (ADA) and Novo Nordisk (NN) Definition: Overall NN: Unclassifiable	6806 Number of hypoglycaemic episodes	7257 Number of hypoglycaemic episodes

SECONDARY outcome

Timeframe: Weeks 0-16

Population: Overall number of participants analyzed = safety analysis set (SAS) which comprised all randomised participants. Number Analyzed = number of participants with available data.

Number of treatment emergent day time hypoglycaemic episodes according to the ADA and NN definitions were evaluated between 06:00 and 00:00 (both included). The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

Outcome measures

Measure	Faster Aspart n=544 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=544 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Daytime Hypoglycaemic Episodes (06:00-00:00 - Inclusive) ADA: Severe	16 Number of hypoglycaemic episodes	12 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Daytime Hypoglycaemic Episodes (06:00-00:00 - Inclusive) ADA: Unclassifiable	3 Number of hypoglycaemic episodes	3 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Daytime Hypoglycaemic Episodes (06:00-00:00 - Inclusive) NN: BG confirmed	2016 Number of hypoglycaemic episodes	2442 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Daytime Hypoglycaemic Episodes (06:00-00:00 - Inclusive) NN: Severe or BG confirmed symptomatic	1333 Number of hypoglycaemic episodes	1814 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Daytime Hypoglycaemic Episodes (06:00-00:00 - Inclusive) NN: Severe or BG confirmed	2032 Number of hypoglycaemic episodes	2454 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Daytime Hypoglycaemic Episodes (06:00-00:00 - Inclusive) NN: Unclassifiable	6510 Number of hypoglycaemic episodes	6875 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Daytime Hypoglycaemic Episodes (06:00-00:00 - Inclusive) Not able to selftreat - unclassifiable	0 Number of hypoglycaemic episodes	0 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Daytime Hypoglycaemic Episodes (06:00-00:00 - Inclusive) ADA: Documented symptomatic	4703 Number of hypoglycaemic episodes	5700 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Daytime Hypoglycaemic Episodes (06:00-00:00 - Inclusive) ADA: Asymptomatic	3617 Number of hypoglycaemic episodes	3484 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Daytime Hypoglycaemic Episodes (06:00-00:00 - Inclusive) ADA: Probable symptomatic	62 Number of hypoglycaemic episodes	64 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Daytime Hypoglycaemic Episodes (06:00-00:00 - Inclusive) ADA: Pseudo	141 Number of hypoglycaemic episodes	66 Number of hypoglycaemic episodes

SECONDARY outcome

Timeframe: Weeks 0-16

Population: Overall number of participants analyzed = safety analysis set (SAS) which comprised all randomised participants. Number Analyzed = number of participants with available data.

Number of treatment emergent nocturnal hypoglycaemic episodes according to the ADA and NN definitions were evaluated between 00:01 and 05:59 (both included). The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

Outcome measures

Measure	Faster Aspart n=544 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=544 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Nocturnal Hypoglycaemic Episodes (00:01-05:59 - Inclusive) ADA: Severe	2 Number of hypoglycaemic episodes	2 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Nocturnal Hypoglycaemic Episodes (00:01-05:59 - Inclusive) ADA: Documented symptomatic	335 Number of hypoglycaemic episodes	465 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Nocturnal Hypoglycaemic Episodes (00:01-05:59 - Inclusive) ADA: Asymptomatic	144 Number of hypoglycaemic episodes	197 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Nocturnal Hypoglycaemic Episodes (00:01-05:59 - Inclusive) ADA: Probable symptomatic	6 Number of hypoglycaemic episodes	4 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Nocturnal Hypoglycaemic Episodes (00:01-05:59 - Inclusive) ADA: Pseudo	4 Number of hypoglycaemic episodes	9 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Nocturnal Hypoglycaemic Episodes (00:01-05:59 - Inclusive) ADA: Unclassifiable	0 Number of hypoglycaemic episodes	0 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Nocturnal Hypoglycaemic Episodes (00:01-05:59 - Inclusive) NN: BG confirmed	193 Number of hypoglycaemic episodes	293 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Nocturnal Hypoglycaemic Episodes (00:01-05:59 - Inclusive) NN: Severe or BG confirmed symptomatic	157 Number of hypoglycaemic episodes	241 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Nocturnal Hypoglycaemic Episodes (00:01-05:59 - Inclusive) NN: Severe or BG confirmed	195 Number of hypoglycaemic episodes	295 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Nocturnal Hypoglycaemic Episodes (00:01-05:59 - Inclusive) NN: Unclassifiable	296 Number of hypoglycaemic episodes	382 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Nocturnal Hypoglycaemic Episodes (00:01-05:59 - Inclusive) Not able to selftreat - unclassifiable	0 Number of hypoglycaemic episodes	0 Number of hypoglycaemic episodes

SECONDARY outcome

Timeframe: Weeks 0-16

Population: Overall number of participants analyzed = safety analysis set (SAS) which comprised all randomised participants. Number Analyzed = number of participants with available data.

Number of treatment emergent hypoglycaemic episodes according to the ADA and NN definitions were evaluated during the first 1 hour after start of the meal. The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

Outcome measures

Measure	Faster Aspart n=544 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=544 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 1 Hour After Start of the Meal ADA: Severe	2 Number of hypoglycaemic episodes	0 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 1 Hour After Start of the Meal ADA: Probable symptomatic	11 Number of hypoglycaemic episodes	8 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 1 Hour After Start of the Meal ADA: Pseudo	2 Number of hypoglycaemic episodes	4 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 1 Hour After Start of the Meal Not able to selftreat - unclassifiable	0 Number of hypoglycaemic episodes	0 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 1 Hour After Start of the Meal ADA: Documented symptomatic	149 Number of hypoglycaemic episodes	148 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 1 Hour After Start of the Meal ADA: Asymptomatic	87 Number of hypoglycaemic episodes	80 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 1 Hour After Start of the Meal ADA: Unclassifiable	0 Number of hypoglycaemic episodes	0 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 1 Hour After Start of the Meal NN: BG confirmed	72 Number of hypoglycaemic episodes	65 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 1 Hour After Start of the Meal NN: Severe or BG confirmed symptomatic	48 Number of hypoglycaemic episodes	50 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 1 Hour After Start of the Meal NN: Severe or BG confirmed	74 Number of hypoglycaemic episodes	65 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 1 Hour After Start of the Meal NN: Unclassifiable	177 Number of hypoglycaemic episodes	175 Number of hypoglycaemic episodes

SECONDARY outcome

Timeframe: Weeks 0-16

Population: Overall number of participants analyzed = safety analysis set (SAS) which comprised all randomised participants. Number Analyzed = number of participants with available data.

Number of treatment emergent hypoglycaemic episodes according to the ADA and NN definitions were evaluated during the first 2 hours after start of the meal. The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

Outcome measures

Measure	Faster Aspart n=544 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=544 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 2 Hours After Start of the Meal ADA: Pseudo	10 Number of hypoglycaemic episodes	7 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 2 Hours After Start of the Meal ADA: Unclassifiable	0 Number of hypoglycaemic episodes	0 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 2 Hours After Start of the Meal NN: BG confirmed	233 Number of hypoglycaemic episodes	246 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 2 Hours After Start of the Meal NN: Unclassifiable	459 Number of hypoglycaemic episodes	377 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 2 Hours After Start of the Meal ADA: Severe	2 Number of hypoglycaemic episodes	1 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 2 Hours After Start of the Meal ADA: Documented symptomatic	465 Number of hypoglycaemic episodes	446 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 2 Hours After Start of the Meal ADA: Asymptomatic	201 Number of hypoglycaemic episodes	159 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 2 Hours After Start of the Meal ADA: Probable symptomatic	16 Number of hypoglycaemic episodes	11 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 2 Hours After Start of the Meal NN: Severe or BG confirmed symptomatic	181 Number of hypoglycaemic episodes	212 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 2 Hours After Start of the Meal NN: Severe or BG confirmed	235 Number of hypoglycaemic episodes	247 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 2 Hours After Start of the Meal Not able to selftreat - unclassifiable	0 Number of hypoglycaemic episodes	0 Number of hypoglycaemic episodes

SECONDARY outcome

Timeframe: Weeks 0-16

Population: Overall number of participants analyzed = safety analysis set (SAS) which comprised all randomised participants. Number Analyzed = number of participants with available data.

Number of treatment emergent hypoglycaemic episodes according to the ADA and NN definitions were evaluated during the first 4 hours after start of the meal. The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

Outcome measures

Measure	Faster Aspart n=544 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=544 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 4 Hours After Start of the Meal ADA: Probable symptomatic	37 Number of hypoglycaemic episodes	27 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 4 Hours After Start of the Meal ADA: Pseudo	55 Number of hypoglycaemic episodes	26 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 4 Hours After Start of the Meal ADA: Unclassifiable	0 Number of hypoglycaemic episodes	0 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 4 Hours After Start of the Meal NN: BG confirmed	762 Number of hypoglycaemic episodes	965 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 4 Hours After Start of the Meal Not able to selftreat - unclassifiable	0 Number of hypoglycaemic episodes	0 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 4 Hours After Start of the Meal ADA: Severe	6 Number of hypoglycaemic episodes	9 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 4 Hours After Start of the Meal ADA: Documented symptomatic	1627 Number of hypoglycaemic episodes	1882 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 4 Hours After Start of the Meal ADA: Asymptomatic	852 Number of hypoglycaemic episodes	744 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 4 Hours After Start of the Meal NN: Severe or BG confirmed symptomatic	557 Number of hypoglycaemic episodes	820 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 4 Hours After Start of the Meal NN: Severe or BG confirmed	768 Number of hypoglycaemic episodes	974 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 4 Hours After Start of the Meal NN: Unclassifiable	1809 Number of hypoglycaemic episodes	1714 Number of hypoglycaemic episodes

SECONDARY outcome

Timeframe: Weeks 0-16

Population: Overall number of participants analyzed = safety analysis set (SAS) which comprised all randomised participants. Number Analyzed = number of participants with available data.

Number of treatment emergent hypoglycaemic episodes according to the ADA and NN definitions were evaluated between 2 to 4 hours after start of the meal. The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

Outcome measures

Measure	Faster Aspart n=544 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=544 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and NN Definition: Hypoglycaemic Episodes Occurring Between 2 to 4 Hours After Start of the Meal ADA: Severe	4 Number of hypoglycaemic episodes	8 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and NN Definition: Hypoglycaemic Episodes Occurring Between 2 to 4 Hours After Start of the Meal ADA: Documented symptomatic	1162 Number of hypoglycaemic episodes	1436 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and NN Definition: Hypoglycaemic Episodes Occurring Between 2 to 4 Hours After Start of the Meal ADA: Asymptomatic	651 Number of hypoglycaemic episodes	585 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and NN Definition: Hypoglycaemic Episodes Occurring Between 2 to 4 Hours After Start of the Meal ADA: Probable symptomatic	21 Number of hypoglycaemic episodes	16 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and NN Definition: Hypoglycaemic Episodes Occurring Between 2 to 4 Hours After Start of the Meal ADA: Pseudo	45 Number of hypoglycaemic episodes	19 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and NN Definition: Hypoglycaemic Episodes Occurring Between 2 to 4 Hours After Start of the Meal ADA: Unclassifiable	0 Number of hypoglycaemic episodes	0 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and NN Definition: Hypoglycaemic Episodes Occurring Between 2 to 4 Hours After Start of the Meal Not able to selftreat - unclassifiable	0 Number of hypoglycaemic episodes	0 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and NN Definition: Hypoglycaemic Episodes Occurring Between 2 to 4 Hours After Start of the Meal NN: BG confirmed	529 Number of hypoglycaemic episodes	719 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and NN Definition: Hypoglycaemic Episodes Occurring Between 2 to 4 Hours After Start of the Meal NN: Severe or BG confirmed symptomatic	376 Number of hypoglycaemic episodes	608 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and NN Definition: Hypoglycaemic Episodes Occurring Between 2 to 4 Hours After Start of the Meal NN: Severe or BG confirmed	533 Number of hypoglycaemic episodes	727 Number of hypoglycaemic episodes
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and NN Definition: Hypoglycaemic Episodes Occurring Between 2 to 4 Hours After Start of the Meal NN: Unclassifiable	1350 Number of hypoglycaemic episodes	1337 Number of hypoglycaemic episodes

SECONDARY outcome

Timeframe: Week 0, week 16

Population: Overall number of participants analyzed = safety analysis set (SAS) which comprised all randomised participants. Number Analyzed = number of participants with available data.

Participants with physical examination findings, normal, abnormal NCS (non- clinically significant) and abnormal CS (clinically significant) at baseline (week 0) and week 16 presented. Results are based on the data from the on-treatment observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. Results are presented for the following examinations: 1) Cardiovascular system 2) Central & Peripheral nervous system 3) Gastrointestinal system incl. mouth 4) Head, ears, eyes, nose, throat and neck 5) Musculoskeletal system 6) Respiratory system 7) Skin

Outcome measures

Measure	Faster Aspart n=544 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=544 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Change From Baseline in Physical Examination Cardiovascular system (week 0) · Normal	459 Participants	460 Participants
Change From Baseline in Physical Examination Cardiovascular system (week 0) · Abnormal NCS	79 Participants	79 Participants
Change From Baseline in Physical Examination Cardiovascular system (week 16) · Abnormal CS	6 Participants	4 Participants
Change From Baseline in Physical Examination Central and Peripheral nervous sys. (week 0) · Normal	398 Participants	404 Participants
Change From Baseline in Physical Examination Central and Peripheral nervous sys. (week 0) · Abnormal NCS	133 Participants	127 Participants
Change From Baseline in Physical Examination Central and Peripheral nervous sys. (week 0) · Abnormal CS	13 Participants	13 Participants
Change From Baseline in Physical Examination Central and Peripheral nervous sys. (week 16) · Normal	383 Participants	400 Participants
Change From Baseline in Physical Examination Gastrointestinal sys. including mouth (week 16) · Abnormal NCS	45 Participants	57 Participants
Change From Baseline in Physical Examination Gastrointestinal sys. including mouth (week 16) · Abnormal CS	0 Participants	0 Participants
Change From Baseline in Physical Examination Head, ears, eyes, nose, throat, neck (week 16) · Normal	485 Participants	483 Participants
Change From Baseline in Physical Examination Musculoskeletal system (week 16) · Abnormal NCS	32 Participants	33 Participants
Change From Baseline in Physical Examination Musculoskeletal system (week 16) · Abnormal CS	4 Participants	6 Participants
Change From Baseline in Physical Examination Respiratory system (week 0) · Normal	535 Participants	534 Participants
Change From Baseline in Physical Examination Respiratory system (week 0) · Abnormal NCS	9 Participants	9 Participants
Change From Baseline in Physical Examination Respiratory system (week 16) · Normal	520 Participants	517 Participants
Change From Baseline in Physical Examination Respiratory system (week 16) · Abnormal NCS	5 Participants	14 Participants
Change From Baseline in Physical Examination Respiratory system (week 16) · Abnormal CS	0 Participants	2 Participants
Change From Baseline in Physical Examination Skin (week 16) · Normal	418 Participants	430 Participants
Change From Baseline in Physical Examination Skin (week 16) · Abnormal NCS	98 Participants	98 Participants
Change From Baseline in Physical Examination Skin (week 16) · Abnormal CS	9 Participants	5 Participants
Change From Baseline in Physical Examination Cardiovascular system (week 0) · Abnormal CS	6 Participants	5 Participants
Change From Baseline in Physical Examination Cardiovascular system (week 16) · Normal	448 Participants	457 Participants
Change From Baseline in Physical Examination Cardiovascular system (week 16) · Abnormal NCS	71 Participants	72 Participants
Change From Baseline in Physical Examination Central and Peripheral nervous sys. (week 16) · Abnormal NCS	128 Participants	122 Participants
Change From Baseline in Physical Examination Central and Peripheral nervous sys. (week 16) · Abnormal CS	14 Participants	11 Participants
Change From Baseline in Physical Examination Gastrointestinal sys. including mouth (Week 0) · Normal	491 Participants	485 Participants
Change From Baseline in Physical Examination Gastrointestinal sys. including mouth (Week 0) · Abnormal NCS	53 Participants	59 Participants
Change From Baseline in Physical Examination Gastrointestinal sys. including mouth (Week 0) · Abnormal CS	0 Participants	0 Participants
Change From Baseline in Physical Examination Gastrointestinal sys. including mouth (week 16) · Normal	480 Participants	476 Participants
Change From Baseline in Physical Examination Head, ears, eyes, nose, throat, neck (week 0) · Normal	498 Participants	492 Participants
Change From Baseline in Physical Examination Head, ears, eyes, nose, throat, neck (week 0) · Abnormal NCS	43 Participants	48 Participants
Change From Baseline in Physical Examination Head, ears, eyes, nose, throat, neck (week 0) · Abnormal CS	3 Participants	4 Participants
Change From Baseline in Physical Examination Head, ears, eyes, nose, throat, neck (week 16) · Abnormal NCS	40 Participants	49 Participants
Change From Baseline in Physical Examination Head, ears, eyes, nose, throat, neck (week 16) · Abnormal CS	0 Participants	1 Participants
Change From Baseline in Physical Examination Musculoskeletal system (week 0) · Normal	504 Participants	496 Participants
Change From Baseline in Physical Examination Musculoskeletal system (week 0) · Abnormal NCS	36 Participants	42 Participants
Change From Baseline in Physical Examination Musculoskeletal system (week 0) · Abnormal CS	4 Participants	6 Participants
Change From Baseline in Physical Examination Musculoskeletal system (week 16) · Normal	489 Participants	494 Participants
Change From Baseline in Physical Examination Respiratory system (week 0) · Abnormal CS	0 Participants	1 Participants
Change From Baseline in Physical Examination Skin (week 0) · Normal	438 Participants	429 Participants
Change From Baseline in Physical Examination Skin (week 0) · Abnormal NCS	96 Participants	108 Participants
Change From Baseline in Physical Examination Skin (week 0) · Abnormal CS	10 Participants	7 Participants

SECONDARY outcome

Timeframe: Week 0, week 16

Population: Overall number of participants analyzed = number of participants with available data.

Change in vital signs - systolic and diastolic blood pressure from baseline (week 0) was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

Outcome measures

Measure	Faster Aspart n=525 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=533 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Change From Baseline in Vital Signs: Systolic and Diastolic Blood Presure Systolic blood pressure	0.4 mmHg Standard Deviation 14.0	-1.2 mmHg Standard Deviation 14.8
Change From Baseline in Vital Signs: Systolic and Diastolic Blood Presure Diastolic blood pressure	-0.4 mmHg Standard Deviation 8.9	-0.7 mmHg Standard Deviation 8.9

SECONDARY outcome

Timeframe: Week 0, week 16

Population: Overall number of participants analyzed = number of participants with available data.

Change in vital signs - pulse from baseline (week 0) was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

Outcome measures

Measure	Faster Aspart n=525 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=533 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Change From Baseline in Vital Signs: Pulse	0.5 Beats per min Standard Deviation 9.0	0.03 Beats per min Standard Deviation 8.9

SECONDARY outcome

Timeframe: Week 0, week 16

Population: Overall number of participants analyzed = safety analysis set (SAS) which comprised all randomised participants. Number Analyzed = number of participants with available data.

Changes in electrocardiogram (ECG) from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

Outcome measures

Measure	Faster Aspart n=544 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=544 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Change From Baseline in Electrocardiogram (ECG) Week 0 · Normal	287 Participants	270 Participants
Change From Baseline in Electrocardiogram (ECG) Week 0 · Abnormal NCS	252 Participants	264 Participants
Change From Baseline in Electrocardiogram (ECG) Week 0 · Abnormal CS	5 Participants	10 Participants
Change From Baseline in Electrocardiogram (ECG) Week 16 · Normal	274 Participants	272 Participants
Change From Baseline in Electrocardiogram (ECG) Week 16 · Abnormal NCS	245 Participants	253 Participants
Change From Baseline in Electrocardiogram (ECG) Week 16 · Abnormal CS	6 Participants	8 Participants

SECONDARY outcome

Timeframe: Week 0, week 16

Population: Overall number of participants analyzed = safety analysis set (SAS) which comprised all randomised participants. Number Analyzed = number of participants with available data.

Changes in fundoscopy/fundus photography from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

Outcome measures

Measure	Faster Aspart n=544 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=544 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Change From Baseline in Fundoscopy/Fundus Photography Left eye (week 0) · Normal	225 Participants	219 Participants
Change From Baseline in Fundoscopy/Fundus Photography Left eye (week 0) · Abnormal NCS	287 Participants	297 Participants
Change From Baseline in Fundoscopy/Fundus Photography Left eye (week 16) · Normal	205 Participants	198 Participants
Change From Baseline in Fundoscopy/Fundus Photography Right eye (week 0) · Normal	224 Participants	217 Participants
Change From Baseline in Fundoscopy/Fundus Photography Right eye (week 0) · Abnormal NCS	288 Participants	300 Participants
Change From Baseline in Fundoscopy/Fundus Photography Right eye (week 0) · Abnormal CS	32 Participants	27 Participants
Change From Baseline in Fundoscopy/Fundus Photography Right eye (week 16) · Normal	208 Participants	194 Participants
Change From Baseline in Fundoscopy/Fundus Photography Right eye (week 16) · Abnormal NCS	276 Participants	297 Participants
Change From Baseline in Fundoscopy/Fundus Photography Right eye (week 16) · Abnormal CS	30 Participants	26 Participants
Change From Baseline in Fundoscopy/Fundus Photography Left eye (week 0) · Abnormal CS	32 Participants	27 Participants
Change From Baseline in Fundoscopy/Fundus Photography Left eye (week 16) · Abnormal NCS	278 Participants	288 Participants
Change From Baseline in Fundoscopy/Fundus Photography Left eye (week 16) · Abnormal CS	31 Participants	30 Participants

SECONDARY outcome

Timeframe: Week 0, week 16

Population: Overall number of participants analyzed = number of participants with available data.

Changes in haematology - haematocrit from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

Outcome measures

Measure	Faster Aspart n=532 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=536 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Change From Baseline in Haematology - Haematocrit	0.48 Percentage Standard Deviation 2.47	0.35 Percentage Standard Deviation 2.47

SECONDARY outcome

Timeframe: Week 0, week 16

Population: Overall number of participants analyzed = number of participants with available data.

Changes in haematology - haemoglobin from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

Outcome measures

Measure	Faster Aspart n=532 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=536 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Change From Baseline in Haematology - Haemoglobin	-0.02 mmol/L Standard Deviation 0.47	-0.04 mmol/L Standard Deviation 0.43

SECONDARY outcome

Timeframe: Week 0, week 16

Population: Overall number of participants analyzed = number of participants with available data.

Changes in haematology - leukocytes from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

Outcome measures

Measure	Faster Aspart n=532 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=536 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Change From Baseline in Haematology - Leukocytes	0.01 10^9 leukocytes/L Standard Deviation 1.60	-0.01 10^9 leukocytes/L Standard Deviation 1.35

SECONDARY outcome

Timeframe: Week 0, week 16

Population: Overall number of participants analyzed = number of participants with available data.

Changes in haematology - thrombocytes from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

Outcome measures

Measure	Faster Aspart n=531 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=533 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Change From Baseline in Haematology - Thrombocytes	-0.9 10^9 thrombocytes/L Standard Deviation 37.1	-1.3 10^9 thrombocytes/L Standard Deviation 38.7

SECONDARY outcome

Timeframe: Week 0, week 16

Population: Overall number of participants analyzed = number of participants with available data.

Changes in haematology - erythrocytes from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

Outcome measures

Measure	Faster Aspart n=532 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=536 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Change From Baseline in Haematology - Erythrocytes	-0.02 10^12 erythrocytes/L Standard Deviation 0.28	-0.04 10^12 erythrocytes/L Standard Deviation 0.27

SECONDARY outcome

Timeframe: Week 0, week 16

Population: Overall number of participants analyzed = number of participants with available data.

Changes in biochemistry - alanine aminotransferase from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

Outcome measures

Measure	Faster Aspart n=532 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=536 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Change From Baseline in Biochemistry - Alanine Aminotransferase (ALT)	-0.1 U/L Standard Deviation 9.4	3.1 U/L Standard Deviation 65.4

SECONDARY outcome

Timeframe: Week 0, week 16

Population: Overall number of participants analyzed = number of participants with available data.

Changes in biochemistry - alkaline phosphatase from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

Outcome measures

Measure	Faster Aspart n=532 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=536 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Change From Baseline in Biochemistry - Alkaline Phosphatase	2.9 U/L Standard Deviation 22.6	2.2 U/L Standard Deviation 18.3

SECONDARY outcome

Timeframe: Week 0, week 16

Population: Overall number of participants analyzed = number of participants with available data.

Changes in biochemistry - aspratate aminotransferase from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

Outcome measures

Measure	Faster Aspart n=532 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=536 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Change From Baseline in Biochemistry - Aspartate Aminotransferase (AST)	-0.2 U/L Standard Deviation 7.9	2.2 U/L Standard Deviation 45.7

SECONDARY outcome

Timeframe: Week 0, week 16

Population: Overall number of participants analyzed = number of participants with available data.

Changes in biochemistry - albumin from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

Outcome measures

Measure	Faster Aspart n=532 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=536 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Change From Baseline in Biochemistry - Albumin	0.02 g/dL Standard Deviation 0.25	0.01 g/dL Standard Deviation 0.26

SECONDARY outcome

Timeframe: Week 0, week 16

Population: Overall number of participants analyzed = number of participants with available data.

Changes in biochemistry - creatinine from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

Outcome measures

Measure	Faster Aspart n=532 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=536 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Change From Baseline in Biochemistry - Creatinine	0.1 umol/L Standard Deviation 11.1	1.5 umol/L Standard Deviation 13.2

SECONDARY outcome

Timeframe: Week 0, week 16

Population: Overall number of participants analyzed = number of participants with available data.

Changes in biochemistry - potassium from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

Outcome measures

Measure	Faster Aspart n=532 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=536 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Change From Baseline in Biochemistry - Potassium	-0.001 mmol/L Standard Deviation 0.50	0.02 mmol/L Standard Deviation 0.43

SECONDARY outcome

Timeframe: Week 0, week 16

Population: Overall number of participants analyzed = number of participants with available data.

Changes in biochemistry - sodium from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

Outcome measures

Measure	Faster Aspart n=532 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=536 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Change From Baseline in Biochemistry - Sodium	-0.6 mmol/L Standard Deviation 2.6	-0.7 mmol/L Standard Deviation 2.8

SECONDARY outcome

Timeframe: Week 0, week 16

Population: Overall number of participants analyzed = number of participants with available data.

Changes in biochemistry - total bilirubin from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

Outcome measures

Measure	Faster Aspart n=531 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=536 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Change From Baseline in Biochemistry - Total Bilirubin	0.1 umol/L Standard Deviation 2.7	0.1 umol/L Standard Deviation 3.0

SECONDARY outcome

Timeframe: Week 0, week 16

Population: Overall number of participants analyzed = number of participants with available data.

Changes in biochemistry - total protein from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

Outcome measures

Measure	Faster Aspart n=532 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=536 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Change From Baseline in Biochemistry - Total Protein	-0.01 g/dL Standard Deviation 0.35	-0.02 g/dL Standard Deviation 0.36

SECONDARY outcome

Timeframe: Week 0, week 16

Population: Overall number of participants analyzed = number of participants with available data.

Changes in body weight from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

Outcome measures

Measure	Faster Aspart n=522 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=530 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Change From Baseline in Body Weight	1.19 kg Standard Deviation 2.95	1.12 kg Standard Deviation 4.01

SECONDARY outcome

Timeframe: Week 0, week 16

Population: Overall number of participants analyzed = number of participants with available data.

Change in the body mass index (BMI) from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.

Outcome measures

Measure	Faster Aspart n=522 Participants Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=530 Participants Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Change From Baseline in Body Mass Index (BMI)	0.43 kg/m^2 Standard Deviation 1.04	0.40 kg/m^2 Standard Deviation 1.40

Adverse Events

Faster Aspart

Serious events: 38 serious events

Other events: 32 other events

Deaths: 2 deaths

NovoRapid

Serious events: 40 serious events

Other events: 33 other events

Deaths: 1 deaths

Serious adverse events

Measure	Faster Aspart n=544 participants at risk Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=544 participants at risk Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Injury, poisoning and procedural complications Accidental overdose	0.37% 2/544 • Number of events 2 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Cardiac disorders Acute coronary syndrome	0.37% 2/544 • Number of events 2 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Renal and urinary disorders Acute kidney injury	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Cardiac disorders Acute myocardial infarction	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma of colon	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Cardiac disorders Angina pectoris	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.37% 2/544 • Number of events 2 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Cardiac disorders Angina unstable	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Vascular disorders Aortic aneurysm	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Surgical and medical procedures Aortic valve replacement	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Cardiac disorders Arteriosclerosis coronary artery	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Musculoskeletal and connective tissue disorders Arthritis	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Cardiac disorders Atrial fibrillation	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Hepatobiliary disorders Bile duct obstruction	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Cardiac disorders Bradycardia	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Infections and infestations Bronchitis	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Cardiac disorders Cardiac failure	0.37% 2/544 • Number of events 2 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Cardiac disorders Cardiac failure congestive	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.37% 2/544 • Number of events 2 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Investigations Cardiac stress test abnormal	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Surgical and medical procedures Carpal tunnel decompression	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Nervous system disorders Cerebellar infarction	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
General disorders Chest pain	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.37% 2/544 • Number of events 2 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Gastrointestinal disorders Colitis	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Injury, poisoning and procedural complications Contusion	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Cardiac disorders Coronary artery disease	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.37% 2/544 • Number of events 2 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Gastrointestinal disorders Cyclic vomiting syndrome	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Vascular disorders Deep vein thrombosis	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Metabolism and nutrition disorders Dehydration	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Psychiatric disorders Delusion	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Product Issues Device malfunction	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Infections and infestations Device related sepsis	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Nervous system disorders Diabetic neuropathy	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Gastrointestinal disorders Diarrhoea	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Nervous system disorders Dizziness	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.37% 2/544 • Number of events 2 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Gastrointestinal disorders Duodenal ulcer	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Nervous system disorders Encephalopathy	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Injury, poisoning and procedural complications Fall	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Injury, poisoning and procedural complications Fibula fracture	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Infections and infestations Gangrene	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.37% 2/544 • Number of events 2 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Gastrointestinal disorders Gastritis erosive	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Infections and infestations Gastroenteritis viral	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Blood and lymphatic system disorders Haemorrhagic anaemia	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Nervous system disorders Haemorrhagic stroke	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Nervous system disorders Headache	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatocellular carcinoma	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Injury, poisoning and procedural complications Humerus fracture	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Metabolism and nutrition disorders Hypoglycaemia	0.74% 4/544 • Number of events 4 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.55% 3/544 • Number of events 3 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Nervous system disorders Hypoglycaemic unconsciousness	0.55% 3/544 • Number of events 3 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Vascular disorders Hypotension	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Infections and infestations Infective exacerbation of chronic obstructive airways disease	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.18% 1/544 • Number of events 2 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive ductal breast carcinoma	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Blood and lymphatic system disorders Iron deficiency anaemia	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Cardiac disorders Left ventricular failure	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Infections and infestations Lower respiratory tract infection	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Cardiac disorders Mitral valve incompetence	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Cardiac disorders Myocardial ischaemia	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Gastrointestinal disorders Obstructive pancreatitis	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Infections and infestations Orchitis	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Infections and infestations Osteomyelitis	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
General disorders Pain	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma metastatic	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Vascular disorders Peripheral vascular disorder	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Infections and infestations Pneumonia	0.37% 2/544 • Number of events 2 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Psychiatric disorders Rapid eye movements sleep abnormal	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Surgical and medical procedures Rehabilitation therapy	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Renal and urinary disorders Renal failure	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Infections and infestations Respiratory tract infection	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.37% 2/544 • Number of events 2 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Gastrointestinal disorders Small intestinal obstruction	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Musculoskeletal and connective tissue disorders Spinal pain	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Vascular disorders Subclavian vein occlusion	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Nervous system disorders Transient ischaemic attack	0.37% 2/544 • Number of events 2 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Musculoskeletal and connective tissue disorders Trigger finger	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Infections and infestations Upper respiratory tract infection	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Vascular disorders Varicose ulceration	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Nervous system disorders Vascular parkinsonism	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Surgical and medical procedures Vitrectomy	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Eye disorders Vitreous haemorrhage	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.00% 0/544 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.
Injury, poisoning and procedural complications Wrong product administered	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	0.18% 1/544 • Number of events 1 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.

Other adverse events

Measure	Faster Aspart n=544 participants at risk Participants received Faster aspart along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. Faster aspart was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.	NovoRapid n=544 participants at risk Participants received Insulin aspart (NovoRapid®/NovoLog®: basal-bolus regimen) along with insulin degludec (basal-bolus regimen) with or without metformin for 16 weeks. Before the treatment period was a 12-week run-in period in which the investigator optimised basal insulin dose. Insulin degludec dose was adjusted weekly by the investigator in the run-in period based on the mean of three pre-breakfast SMPG values measured on the last two days prior to and on the day of contact. If one of the SMPG values were below target (\< 4.0 mmol/L or 71 mg/dL) then the insulin degludec dose was adjusted according to the titration guideline specified in the protocol. NovoRapid was titrated from randomisation (week 0) and onwards, twice weekly to reach the glycaemic target of pre-prandial and bedtime PG between 4.0-6.0 mmol/L (71 - 108 mg/dL) in a treat-to-target fashion.
Infections and infestations Nasopharyngitis	5.9% 32/544 • Number of events 35 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.	6.1% 33/544 • Number of events 36 • Week 0 to Week 16 + 7 days. All reported adverse events (AEs) are treatment emergent (i.e., TEAE). All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants receiving at least one dose of randomised treatment.

Additional Information

Clinical Reporting Anchor and Disclosure (1452)

Novo Nordisk A/S

Phone: (+1) 866-867-7178

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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