Trial Outcomes & Findings for Efficacy and Safety of FIAsp Compared to Insulin Aspart Both in Combination With Insulin Detemir in Adults With Type 1 Diabetes (NCT NCT01831765)

NCT ID: NCT01831765

Last Updated: 2019-06-12

Results Overview

Change from baseline in HbA1c after 26 weeks of randomised treatment.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1290 participants

Primary outcome timeframe

Week 0, week 26

Results posted on

2019-06-12

Participant Flow

Out of 281 sites, selected for recruitment, 165 sites in 9 countries enrolled subjects in the run-in period, of which 163 sites later assigned subjects to randomised treatment: Belgium:5 sites, Canada:12 sites, Czech Republic:5 sites; Finland:6 sites; Germany:25 sites; Hungary:5 sites; Poland:6 sites; United Kingdom:9 sites; United States:92 sites.

Eligible subjects received once/twice daily insulin detemir and NovoRapid®/NovoLog® during 8 week run-in period. In total, 1290 subjects entered the run-in period, of those147 subjects were run-in failures. Hence 1143 subjects entered the 26-week treatment period followed by a 26 week additional treatment period.

Participant milestones

Participant milestones
Measure	Faster Aspart (Meal) The subjects in this arm were administered mealtime faster aspart (100 U/mL) in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period + a 26-week additional treatment period. Mealtime faster aspart was administered subcutaneously (s.c., under the skin) 0-2 minutes before each main meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.	Faster Aspart (Post) The subjects in this arm were administered postmeal faster aspart (100 U/mL) in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period. Postmeal faster aspart was administered subcutaneously (s.c., under the skin) 20 minutes after the start of the meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.	NovoRapid (Meal) The subjects in this arm were administered mealtime NovoRapid®/NovoLog®, 100 U/mL in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period + a 26-week additional treatment period. Mealtime NovoRapid®/NovoLog® was administered subcutaneously (s.c., under the skin) 0-2 minutes before each main meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.
Overall Study STARTED	381	382	380
Overall Study Completed 26 Weeks	351	355	356
Overall Study Completed 52 Weeks	337	0	338
Overall Study COMPLETED	337	355	338
Overall Study NOT COMPLETED	44	27	42

Reasons for withdrawal

Reasons for withdrawal
Measure	Faster Aspart (Meal) The subjects in this arm were administered mealtime faster aspart (100 U/mL) in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period + a 26-week additional treatment period. Mealtime faster aspart was administered subcutaneously (s.c., under the skin) 0-2 minutes before each main meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.	Faster Aspart (Post) The subjects in this arm were administered postmeal faster aspart (100 U/mL) in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period. Postmeal faster aspart was administered subcutaneously (s.c., under the skin) 20 minutes after the start of the meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.	NovoRapid (Meal) The subjects in this arm were administered mealtime NovoRapid®/NovoLog®, 100 U/mL in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period + a 26-week additional treatment period. Mealtime NovoRapid®/NovoLog® was administered subcutaneously (s.c., under the skin) 0-2 minutes before each main meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.
Overall Study Lack of Efficacy	1	0	0
Overall Study Other, sponsor withdrew subject	0	1	0
Overall Study Pregnancy	1	1	2
Overall Study Death	0	1	1
Overall Study Other, site closed	1	1	0
Overall Study Adverse Event	5	3	3
Overall Study Withdrawal by Subject	22	7	17
Overall Study Withdrawal criteria	12	10	16
Overall Study Lost to Follow-up	2	3	3

Baseline Characteristics

Efficacy and Safety of FIAsp Compared to Insulin Aspart Both in Combination With Insulin Detemir in Adults With Type 1 Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Faster Aspart (Meal) n=381 Participants The subjects in this arm were administered mealtime faster aspart (100 U/mL) in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period + a 26-week additional treatment period. Mealtime faster aspart was administered subcutaneously (s.c., under the skin) 0-2 minutes before each main meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.	Faster Aspart (Post) n=382 Participants The subjects in this arm were administered postmeal faster aspart (100 U/mL) in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period. Postmeal faster aspart was administered subcutaneously (s.c., under the skin) 20 minutes after the start of the meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.	NovoRapid (Meal) n=380 Participants The subjects in this arm were administered mealtime NovoRapid®/NovoLog®, 100 U/mL in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period + a 26-week additional treatment period. Mealtime NovoRapid®/NovoLog® was administered subcutaneously (s.c., under the skin) 0-2 minutes before each main meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.	Total n=1143 Participants Total of all reporting groups
Age, Continuous	46.1 Years STANDARD_DEVIATION 13.8 • n=5 Participants	43.5 Years STANDARD_DEVIATION 13.7 • n=7 Participants	43.7 Years STANDARD_DEVIATION 14 • n=5 Participants	44.4 Years STANDARD_DEVIATION 13.9 • n=4 Participants
Age, Customized Adults (18-64 years)	346 Participants n=5 Participants	359 Participants n=7 Participants	352 Participants n=5 Participants	1057 Participants n=4 Participants
Age, Customized From 65-85 years	35 Participants n=5 Participants	23 Participants n=7 Participants	28 Participants n=5 Participants	86 Participants n=4 Participants
Sex: Female, Male Female	166 Participants n=5 Participants	163 Participants n=7 Participants	142 Participants n=5 Participants	471 Participants n=4 Participants
Sex: Female, Male Male	215 Participants n=5 Participants	219 Participants n=7 Participants	238 Participants n=5 Participants	672 Participants n=4 Participants
Body Weight	78.56 Kg STANDARD_DEVIATION 14.89 • n=5 Participants	80.49 Kg STANDARD_DEVIATION 15.93 • n=7 Participants	80.15 Kg STANDARD_DEVIATION 15.21 • n=5 Participants	79.73 Kg STANDARD_DEVIATION 15.36 • n=4 Participants
Glycosylated haemoglobin (HbA1c)	7.62 Percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.71 • n=5 Participants	7.63 Percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.72 • n=7 Participants	7.58 Percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.68 • n=5 Participants	7.61 Percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.70 • n=4 Participants

PRIMARY outcome

Timeframe: Week 0, week 26

Population: The FAS included all randomised subjects. For this endpoint, baseline and week 26 have been presented, where week 26 data is end of trial containing last available measurement.

Change from baseline in HbA1c after 26 weeks of randomised treatment.

Outcome measures

Outcome measures
Measure	Faster Aspart (Meal) n=381 Participants The subjects in this arm were administered mealtime faster aspart (100 U/mL) in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period + a 26-week additional treatment period. Mealtime faster aspart was administered subcutaneously (s.c., under the skin) 0-2 minutes before each main meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.	Faster Aspart (Post) n=382 Participants The subjects in this arm were administered postmeal faster aspart (100 U/mL) in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period. Postmeal faster aspart was administered subcutaneously (s.c., under the skin) 20 minutes after the start of the meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.	NovoRapid (Meal) n=380 Participants The subjects in this arm were administered mealtime NovoRapid®/NovoLog®, 100 U/mL in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period + a 26-week additional treatment period. Mealtime NovoRapid®/NovoLog® was administered subcutaneously (s.c., under the skin) 0-2 minutes before each main meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.
Change From Baseline in HbA1c (Glycosylated Haemoglobin) Week 0 (Baseline)	7.62 Percentage of glycosylated haemoglobin Standard Deviation 0.71	7.63 Percentage of glycosylated haemoglobin Standard Deviation 0.72	7.58 Percentage of glycosylated haemoglobin Standard Deviation 0.68
Change From Baseline in HbA1c (Glycosylated Haemoglobin) Week 26	7.31 Percentage of glycosylated haemoglobin Standard Deviation 0.77	7.51 Percentage of glycosylated haemoglobin Standard Deviation 0.77	7.42 Percentage of glycosylated haemoglobin Standard Deviation 0.78

SECONDARY outcome

Timeframe: Week 0, week 26

Population: The FAS included all randomised subjects. For this endpoint, baseline and week 26 have been presented, where week 26 data is end of trial containing last available measurement. At baseline (week 0) 379, 377, 375 and 381, 382, 380 subjects at week 26 were analysed for faster aspart (meal), faster aspart (post) and Novorapid (meal) arms respectively.

Change from baseline in 2-hour PPG increments after 26 weeks of randomised treatment (meal test).

Outcome measures

Outcome measures
Measure	Faster Aspart (Meal) n=381 Participants The subjects in this arm were administered mealtime faster aspart (100 U/mL) in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period + a 26-week additional treatment period. Mealtime faster aspart was administered subcutaneously (s.c., under the skin) 0-2 minutes before each main meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.	Faster Aspart (Post) n=382 Participants The subjects in this arm were administered postmeal faster aspart (100 U/mL) in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period. Postmeal faster aspart was administered subcutaneously (s.c., under the skin) 20 minutes after the start of the meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.	NovoRapid (Meal) n=380 Participants The subjects in this arm were administered mealtime NovoRapid®/NovoLog®, 100 U/mL in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period + a 26-week additional treatment period. Mealtime NovoRapid®/NovoLog® was administered subcutaneously (s.c., under the skin) 0-2 minutes before each main meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.
Change From Baseline in 2-hour PPG (Postprandial Glucose) Increment (Meal Test) Week 0: Baseline	6.06 mmol/L Standard Deviation 5.16	6.06 mmol/L Standard Deviation 4.9	6.24 mmol/L Standard Deviation 4.81
Change From Baseline in 2-hour PPG (Postprandial Glucose) Increment (Meal Test) Week 26	5.88 mmol/L Standard Deviation 4.67	6.73 mmol/L Standard Deviation 4.67	6.55 mmol/L Standard Deviation 4.78

SECONDARY outcome

Timeframe: Week 0, week 26

Population: This endpoint was summarised using the FAS, which included all randomised subjects. For this endpoint, baseline and week 26 have been presented, where week 26 data is end of trial containing last available measurement.

Change from baseline in HbA1c (post meal arm) after 26 weeks of randomised treatment.

Outcome measures

Outcome measures
Measure	Faster Aspart (Meal) n=382 Participants The subjects in this arm were administered mealtime faster aspart (100 U/mL) in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period + a 26-week additional treatment period. Mealtime faster aspart was administered subcutaneously (s.c., under the skin) 0-2 minutes before each main meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.	Faster Aspart (Post) n=380 Participants The subjects in this arm were administered postmeal faster aspart (100 U/mL) in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period. Postmeal faster aspart was administered subcutaneously (s.c., under the skin) 20 minutes after the start of the meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.	NovoRapid (Meal) The subjects in this arm were administered mealtime NovoRapid®/NovoLog®, 100 U/mL in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period + a 26-week additional treatment period. Mealtime NovoRapid®/NovoLog® was administered subcutaneously (s.c., under the skin) 0-2 minutes before each main meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.
Change From Baseline in HbA1c (Post Meal Arm) Week 0 (baseline)	7.63 Percentage of glycosylated haemoglobin Standard Deviation 0.72	7.58 Percentage of glycosylated haemoglobin Standard Deviation 0.68	—
Change From Baseline in HbA1c (Post Meal Arm) Week 26	7.51 Percentage of glycosylated haemoglobin Standard Deviation 0.77	7.42 Percentage of glycosylated haemoglobin Standard Deviation 0.78	—

SECONDARY outcome

Timeframe: From baseline until week 26

Population: The safety analysis set included all subjects receiving at least one dose of trial product/its comparator and contributed to the evaluation "as treated". Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).

Observed rate of treatment emergent severe or BG confirmed hypoglycaemic events per 100 patient years of exposure (PYE) from baseline until week 26. A hypoglycaemic episode was defined as treatment emergent if the onset of the episode was on or after the first day of exposure to randomised treatment and no later than 1 day after the last day of randomised treatment. Severe or BG confirmed is an episode that is severe according to the American Diabetes Association (ADA) classification (an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or BG confirmed by a PG value \<3.1 mmol/L (56 mg/dL) with or without symptoms consistent with hypoglycaemia.

Outcome measures

Outcome measures
Measure	Faster Aspart (Meal) n=386 Participants The subjects in this arm were administered mealtime faster aspart (100 U/mL) in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period + a 26-week additional treatment period. Mealtime faster aspart was administered subcutaneously (s.c., under the skin) 0-2 minutes before each main meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.	Faster Aspart (Post) n=377 Participants The subjects in this arm were administered postmeal faster aspart (100 U/mL) in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period. Postmeal faster aspart was administered subcutaneously (s.c., under the skin) 20 minutes after the start of the meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.	NovoRapid (Meal) n=380 Participants The subjects in this arm were administered mealtime NovoRapid®/NovoLog®, 100 U/mL in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period + a 26-week additional treatment period. Mealtime NovoRapid®/NovoLog® was administered subcutaneously (s.c., under the skin) 0-2 minutes before each main meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.
Number of Treatment Emergent Confirmed Hypoglycaemic Episodes	5899 event rate/100 patient yrs of exposure	5443 event rate/100 patient yrs of exposure	5865 event rate/100 patient yrs of exposure

SECONDARY outcome

Timeframe: Week 0, week 26

Population: The FAS included all randomised subjects. For this endpoint baseline, and week 26 have been presented, where week 26 data is end of trial containing last available measurement. At baseline (week 0) 381, 382, 378 and 381, 382, 380 subjects at week 26 were analysed for faster aspart (meal), faster aspart (post) and Novorapid (meal) arms respectively.

Change from baseline in body weight after 26 weeks of randomised treatment.

Outcome measures

Outcome measures
Measure	Faster Aspart (Meal) n=381 Participants The subjects in this arm were administered mealtime faster aspart (100 U/mL) in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period + a 26-week additional treatment period. Mealtime faster aspart was administered subcutaneously (s.c., under the skin) 0-2 minutes before each main meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.	Faster Aspart (Post) n=382 Participants The subjects in this arm were administered postmeal faster aspart (100 U/mL) in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period. Postmeal faster aspart was administered subcutaneously (s.c., under the skin) 20 minutes after the start of the meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.	NovoRapid (Meal) n=380 Participants The subjects in this arm were administered mealtime NovoRapid®/NovoLog®, 100 U/mL in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period + a 26-week additional treatment period. Mealtime NovoRapid®/NovoLog® was administered subcutaneously (s.c., under the skin) 0-2 minutes before each main meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.
Change From Baseline in Body Weight Week 26	79.21 Kg Standard Deviation 15.25	81.17 Kg Standard Deviation 16.45	80.69 Kg Standard Deviation 15.44
Change From Baseline in Body Weight Week 0: Baseline	78.56 Kg Standard Deviation 14.89	80.49 Kg Standard Deviation 15.93	80.15 Kg Standard Deviation 15.21

SECONDARY outcome

Timeframe: After 52 weeks of randomised treatment

All treatment emergent adverse events (TEAEs) from baseline until 52 weeks of randomised treatment. A TEAE was defined as an event that had an onset date on or after the first day of exposure to randomised treatment, and no later than 7 days after the last day of randomised treatment.

Outcome measures

Outcome measures
Measure	Faster Aspart (Meal) n=386 Participants The subjects in this arm were administered mealtime faster aspart (100 U/mL) in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period + a 26-week additional treatment period. Mealtime faster aspart was administered subcutaneously (s.c., under the skin) 0-2 minutes before each main meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.	Faster Aspart (Post) n=377 Participants The subjects in this arm were administered postmeal faster aspart (100 U/mL) in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period. Postmeal faster aspart was administered subcutaneously (s.c., under the skin) 20 minutes after the start of the meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.	NovoRapid (Meal) n=380 Participants The subjects in this arm were administered mealtime NovoRapid®/NovoLog®, 100 U/mL in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period + a 26-week additional treatment period. Mealtime NovoRapid®/NovoLog® was administered subcutaneously (s.c., under the skin) 0-2 minutes before each main meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.
Frequency of Adverse Events	445.8 event /100 patient yrs of exposure	441 event /100 patient yrs of exposure	411 event /100 patient yrs of exposure

SECONDARY outcome

Timeframe: Week 0, week 52

Population: The FAS included all randomised subjects. The statistical evaluation of the FAS was to follow the ITT principle and subjects contributed to the evaluation 'as randomised'. For this endpoint, baseline and week 52 have been presented, where week 52 data is the end of trial containing last available measurement.

Change from baseline in HbA1c (%) after 52 weeks of randomised treatment.

Outcome measures

Outcome measures
Measure	Faster Aspart (Meal) n=381 Participants The subjects in this arm were administered mealtime faster aspart (100 U/mL) in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period + a 26-week additional treatment period. Mealtime faster aspart was administered subcutaneously (s.c., under the skin) 0-2 minutes before each main meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.	Faster Aspart (Post) n=380 Participants The subjects in this arm were administered postmeal faster aspart (100 U/mL) in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period. Postmeal faster aspart was administered subcutaneously (s.c., under the skin) 20 minutes after the start of the meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.	NovoRapid (Meal) The subjects in this arm were administered mealtime NovoRapid®/NovoLog®, 100 U/mL in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period + a 26-week additional treatment period. Mealtime NovoRapid®/NovoLog® was administered subcutaneously (s.c., under the skin) 0-2 minutes before each main meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.
Change in HbA1c Week 0 (baseline)	7.62 Percentage of glycosylated haemoglobin Standard Deviation 0.71	7.58 Percentage of glycosylated haemoglobin Standard Deviation 0.68	—
Change in HbA1c Week 52	7.51 Percentage of glycosylated haemoglobin Standard Deviation 0.83	7.58 Percentage of glycosylated haemoglobin Standard Deviation 0.86	—

SECONDARY outcome

Timeframe: Week 0, week 52

Population: The FAS included all randomised subjects. The number of subjects with data available for PPG at 120 mins at baseline were 379, 379 and 380, 380 at week 52 and for PPG increment (120 mins) at baseline were 379, 375 and 381, 380 at week 26 for faster aspart (meal) and Novorapid (meal) respectively.

Change from baseline in PPG and PPG increment (meal test) after 52 weeks of randomised treatment.

Outcome measures

Outcome measures
Measure	Faster Aspart (Meal) n=381 Participants The subjects in this arm were administered mealtime faster aspart (100 U/mL) in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period + a 26-week additional treatment period. Mealtime faster aspart was administered subcutaneously (s.c., under the skin) 0-2 minutes before each main meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.	Faster Aspart (Post) n=380 Participants The subjects in this arm were administered postmeal faster aspart (100 U/mL) in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period. Postmeal faster aspart was administered subcutaneously (s.c., under the skin) 20 minutes after the start of the meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.	NovoRapid (Meal) The subjects in this arm were administered mealtime NovoRapid®/NovoLog®, 100 U/mL in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period + a 26-week additional treatment period. Mealtime NovoRapid®/NovoLog® was administered subcutaneously (s.c., under the skin) 0-2 minutes before each main meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.
Change in PPG (Postprandial Glucose) PPG at 120 minutes (Baseline)	14.51 mmol/L Standard Deviation 6.09	14.14 mmol/L Standard Deviation 5.69	—
Change in PPG (Postprandial Glucose) PPG at 120 minutes (Week 52)	14.26 mmol/L Standard Deviation 5.76	14.51 mmol/L Standard Deviation 6.02	—
Change in PPG (Postprandial Glucose) PPG increment at 120 mins (Baseline)	6.06 mmol/L Standard Deviation 5.16	6.24 mmol/L Standard Deviation 4.81	—
Change in PPG (Postprandial Glucose) PPG increment at 120 mins(Week 52)	5.71 mmol/L Standard Deviation 4.92	6.14 mmol/L Standard Deviation 4.86	—

Adverse Events

Faster Aspart (Meal)

Serious events: 35 serious events

Other events: 252 other events

Deaths: 0 deaths

Faster Aspart (Post)

Serious events: 28 serious events

Other events: 189 other events

Deaths: 0 deaths

NovoRapid (Meal)

Serious events: 33 serious events

Other events: 236 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Faster Aspart (Meal) n=386 participants at risk The subjects in this arm were administered mealtime faster aspart (100 U/mL) in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period + a 26-week additional treatment period. Mealtime faster aspart was administered subcutaneously (s.c., under the skin) 0-2 minutes before each main meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.	Faster Aspart (Post) n=377 participants at risk The subjects in this arm were administered postmeal faster aspart (100 U/mL) in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period. Postmeal faster aspart was administered subcutaneously (s.c., under the skin) 20 minutes after the start of the meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.	NovoRapid (Meal) n=380 participants at risk The subjects in this arm were administered mealtime NovoRapid®/NovoLog®, 100 U/mL in combination with once or twice daily insulin detemir (100 U/mL) in a basal-bolus regimen for an initial 26 weeks treatment period + a 26-week additional treatment period. Mealtime NovoRapid®/NovoLog® was administered subcutaneously (s.c., under the skin) 0-2 minutes before each main meal. Subjects who, prior to screening, had used the principles of flexible dosing based on the meal carbohydrate content, and who were assessed by the investigator to be adequately trained in this method, were to continue using this method for bolus adjustment during the treatment period. All other subjects were to use a predefined bolus dosing algorithm to adjust the bolus dose during the treatment period. Additional bolus dosing was allowed at the investigator's recommendation.
Musculoskeletal and connective tissue disorders Back pain	7.3% 28/386 • Number of events 36 • Until 52 weeks (26+26) weeks of treatment + 7 days followup for faster aspart (meal) and NovoRapid®(meal) or until 26 weeks of treatment + 7 days followup for faster aspart (post) + 30 day follow-up period for cardio-vascular related events. The safety analysis set included all subjects receiving at least one dose of trial product/ its comparator and contributed to the evaluation "as treated". A TEAE was defined as an event recorded from the first day of exposure to trial product and no later than post-treatment follow-up visit (7 days). Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).	4.0% 15/377 • Number of events 17 • Until 52 weeks (26+26) weeks of treatment + 7 days followup for faster aspart (meal) and NovoRapid®(meal) or until 26 weeks of treatment + 7 days followup for faster aspart (post) + 30 day follow-up period for cardio-vascular related events. The safety analysis set included all subjects receiving at least one dose of trial product/ its comparator and contributed to the evaluation "as treated". A TEAE was defined as an event recorded from the first day of exposure to trial product and no later than post-treatment follow-up visit (7 days). Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).	5.3% 20/380 • Number of events 22 • Until 52 weeks (26+26) weeks of treatment + 7 days followup for faster aspart (meal) and NovoRapid®(meal) or until 26 weeks of treatment + 7 days followup for faster aspart (post) + 30 day follow-up period for cardio-vascular related events. The safety analysis set included all subjects receiving at least one dose of trial product/ its comparator and contributed to the evaluation "as treated". A TEAE was defined as an event recorded from the first day of exposure to trial product and no later than post-treatment follow-up visit (7 days). Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).
Respiratory, thoracic and mediastinal disorders Cough	4.4% 17/386 • Number of events 21 • Until 52 weeks (26+26) weeks of treatment + 7 days followup for faster aspart (meal) and NovoRapid®(meal) or until 26 weeks of treatment + 7 days followup for faster aspart (post) + 30 day follow-up period for cardio-vascular related events. The safety analysis set included all subjects receiving at least one dose of trial product/ its comparator and contributed to the evaluation "as treated". A TEAE was defined as an event recorded from the first day of exposure to trial product and no later than post-treatment follow-up visit (7 days). Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).	3.2% 12/377 • Number of events 13 • Until 52 weeks (26+26) weeks of treatment + 7 days followup for faster aspart (meal) and NovoRapid®(meal) or until 26 weeks of treatment + 7 days followup for faster aspart (post) + 30 day follow-up period for cardio-vascular related events. The safety analysis set included all subjects receiving at least one dose of trial product/ its comparator and contributed to the evaluation "as treated". A TEAE was defined as an event recorded from the first day of exposure to trial product and no later than post-treatment follow-up visit (7 days). Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).	5.3% 20/380 • Number of events 21 • Until 52 weeks (26+26) weeks of treatment + 7 days followup for faster aspart (meal) and NovoRapid®(meal) or until 26 weeks of treatment + 7 days followup for faster aspart (post) + 30 day follow-up period for cardio-vascular related events. The safety analysis set included all subjects receiving at least one dose of trial product/ its comparator and contributed to the evaluation "as treated". A TEAE was defined as an event recorded from the first day of exposure to trial product and no later than post-treatment follow-up visit (7 days). Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).
Gastrointestinal disorders Diarrhoea	7.0% 27/386 • Number of events 34 • Until 52 weeks (26+26) weeks of treatment + 7 days followup for faster aspart (meal) and NovoRapid®(meal) or until 26 weeks of treatment + 7 days followup for faster aspart (post) + 30 day follow-up period for cardio-vascular related events. The safety analysis set included all subjects receiving at least one dose of trial product/ its comparator and contributed to the evaluation "as treated". A TEAE was defined as an event recorded from the first day of exposure to trial product and no later than post-treatment follow-up visit (7 days). Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).	2.9% 11/377 • Number of events 11 • Until 52 weeks (26+26) weeks of treatment + 7 days followup for faster aspart (meal) and NovoRapid®(meal) or until 26 weeks of treatment + 7 days followup for faster aspart (post) + 30 day follow-up period for cardio-vascular related events. The safety analysis set included all subjects receiving at least one dose of trial product/ its comparator and contributed to the evaluation "as treated". A TEAE was defined as an event recorded from the first day of exposure to trial product and no later than post-treatment follow-up visit (7 days). Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).	7.1% 27/380 • Number of events 33 • Until 52 weeks (26+26) weeks of treatment + 7 days followup for faster aspart (meal) and NovoRapid®(meal) or until 26 weeks of treatment + 7 days followup for faster aspart (post) + 30 day follow-up period for cardio-vascular related events. The safety analysis set included all subjects receiving at least one dose of trial product/ its comparator and contributed to the evaluation "as treated". A TEAE was defined as an event recorded from the first day of exposure to trial product and no later than post-treatment follow-up visit (7 days). Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).
Infections and infestations Gastroenteritis	5.2% 20/386 • Number of events 25 • Until 52 weeks (26+26) weeks of treatment + 7 days followup for faster aspart (meal) and NovoRapid®(meal) or until 26 weeks of treatment + 7 days followup for faster aspart (post) + 30 day follow-up period for cardio-vascular related events. The safety analysis set included all subjects receiving at least one dose of trial product/ its comparator and contributed to the evaluation "as treated". A TEAE was defined as an event recorded from the first day of exposure to trial product and no later than post-treatment follow-up visit (7 days). Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).	2.1% 8/377 • Number of events 8 • Until 52 weeks (26+26) weeks of treatment + 7 days followup for faster aspart (meal) and NovoRapid®(meal) or until 26 weeks of treatment + 7 days followup for faster aspart (post) + 30 day follow-up period for cardio-vascular related events. The safety analysis set included all subjects receiving at least one dose of trial product/ its comparator and contributed to the evaluation "as treated". A TEAE was defined as an event recorded from the first day of exposure to trial product and no later than post-treatment follow-up visit (7 days). Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).	4.5% 17/380 • Number of events 21 • Until 52 weeks (26+26) weeks of treatment + 7 days followup for faster aspart (meal) and NovoRapid®(meal) or until 26 weeks of treatment + 7 days followup for faster aspart (post) + 30 day follow-up period for cardio-vascular related events. The safety analysis set included all subjects receiving at least one dose of trial product/ its comparator and contributed to the evaluation "as treated". A TEAE was defined as an event recorded from the first day of exposure to trial product and no later than post-treatment follow-up visit (7 days). Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).
Nervous system disorders Headache	9.6% 37/386 • Number of events 70 • Until 52 weeks (26+26) weeks of treatment + 7 days followup for faster aspart (meal) and NovoRapid®(meal) or until 26 weeks of treatment + 7 days followup for faster aspart (post) + 30 day follow-up period for cardio-vascular related events. The safety analysis set included all subjects receiving at least one dose of trial product/ its comparator and contributed to the evaluation "as treated". A TEAE was defined as an event recorded from the first day of exposure to trial product and no later than post-treatment follow-up visit (7 days). Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).	6.9% 26/377 • Number of events 41 • Until 52 weeks (26+26) weeks of treatment + 7 days followup for faster aspart (meal) and NovoRapid®(meal) or until 26 weeks of treatment + 7 days followup for faster aspart (post) + 30 day follow-up period for cardio-vascular related events. The safety analysis set included all subjects receiving at least one dose of trial product/ its comparator and contributed to the evaluation "as treated". A TEAE was defined as an event recorded from the first day of exposure to trial product and no later than post-treatment follow-up visit (7 days). Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).	11.8% 45/380 • Number of events 79 • Until 52 weeks (26+26) weeks of treatment + 7 days followup for faster aspart (meal) and NovoRapid®(meal) or until 26 weeks of treatment + 7 days followup for faster aspart (post) + 30 day follow-up period for cardio-vascular related events. The safety analysis set included all subjects receiving at least one dose of trial product/ its comparator and contributed to the evaluation "as treated". A TEAE was defined as an event recorded from the first day of exposure to trial product and no later than post-treatment follow-up visit (7 days). Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).
Infections and infestations Influenza	5.7% 22/386 • Number of events 30 • Until 52 weeks (26+26) weeks of treatment + 7 days followup for faster aspart (meal) and NovoRapid®(meal) or until 26 weeks of treatment + 7 days followup for faster aspart (post) + 30 day follow-up period for cardio-vascular related events. The safety analysis set included all subjects receiving at least one dose of trial product/ its comparator and contributed to the evaluation "as treated". A TEAE was defined as an event recorded from the first day of exposure to trial product and no later than post-treatment follow-up visit (7 days). Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).	2.9% 11/377 • Number of events 12 • Until 52 weeks (26+26) weeks of treatment + 7 days followup for faster aspart (meal) and NovoRapid®(meal) or until 26 weeks of treatment + 7 days followup for faster aspart (post) + 30 day follow-up period for cardio-vascular related events. The safety analysis set included all subjects receiving at least one dose of trial product/ its comparator and contributed to the evaluation "as treated". A TEAE was defined as an event recorded from the first day of exposure to trial product and no later than post-treatment follow-up visit (7 days). Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).	9.7% 37/380 • Number of events 54 • Until 52 weeks (26+26) weeks of treatment + 7 days followup for faster aspart (meal) and NovoRapid®(meal) or until 26 weeks of treatment + 7 days followup for faster aspart (post) + 30 day follow-up period for cardio-vascular related events. The safety analysis set included all subjects receiving at least one dose of trial product/ its comparator and contributed to the evaluation "as treated". A TEAE was defined as an event recorded from the first day of exposure to trial product and no later than post-treatment follow-up visit (7 days). Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).
Infections and infestations Nasopharyngitis	33.2% 128/386 • Number of events 214 • Until 52 weeks (26+26) weeks of treatment + 7 days followup for faster aspart (meal) and NovoRapid®(meal) or until 26 weeks of treatment + 7 days followup for faster aspart (post) + 30 day follow-up period for cardio-vascular related events. The safety analysis set included all subjects receiving at least one dose of trial product/ its comparator and contributed to the evaluation "as treated". A TEAE was defined as an event recorded from the first day of exposure to trial product and no later than post-treatment follow-up visit (7 days). Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).	23.9% 90/377 • Number of events 111 • Until 52 weeks (26+26) weeks of treatment + 7 days followup for faster aspart (meal) and NovoRapid®(meal) or until 26 weeks of treatment + 7 days followup for faster aspart (post) + 30 day follow-up period for cardio-vascular related events. The safety analysis set included all subjects receiving at least one dose of trial product/ its comparator and contributed to the evaluation "as treated". A TEAE was defined as an event recorded from the first day of exposure to trial product and no later than post-treatment follow-up visit (7 days). Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).	31.6% 120/380 • Number of events 174 • Until 52 weeks (26+26) weeks of treatment + 7 days followup for faster aspart (meal) and NovoRapid®(meal) or until 26 weeks of treatment + 7 days followup for faster aspart (post) + 30 day follow-up period for cardio-vascular related events. The safety analysis set included all subjects receiving at least one dose of trial product/ its comparator and contributed to the evaluation "as treated". A TEAE was defined as an event recorded from the first day of exposure to trial product and no later than post-treatment follow-up visit (7 days). Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).
Gastrointestinal disorders Nausea	7.3% 28/386 • Number of events 36 • Until 52 weeks (26+26) weeks of treatment + 7 days followup for faster aspart (meal) and NovoRapid®(meal) or until 26 weeks of treatment + 7 days followup for faster aspart (post) + 30 day follow-up period for cardio-vascular related events. The safety analysis set included all subjects receiving at least one dose of trial product/ its comparator and contributed to the evaluation "as treated". A TEAE was defined as an event recorded from the first day of exposure to trial product and no later than post-treatment follow-up visit (7 days). Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).	4.8% 18/377 • Number of events 29 • Until 52 weeks (26+26) weeks of treatment + 7 days followup for faster aspart (meal) and NovoRapid®(meal) or until 26 weeks of treatment + 7 days followup for faster aspart (post) + 30 day follow-up period for cardio-vascular related events. The safety analysis set included all subjects receiving at least one dose of trial product/ its comparator and contributed to the evaluation "as treated". A TEAE was defined as an event recorded from the first day of exposure to trial product and no later than post-treatment follow-up visit (7 days). Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).	6.1% 23/380 • Number of events 34 • Until 52 weeks (26+26) weeks of treatment + 7 days followup for faster aspart (meal) and NovoRapid®(meal) or until 26 weeks of treatment + 7 days followup for faster aspart (post) + 30 day follow-up period for cardio-vascular related events. The safety analysis set included all subjects receiving at least one dose of trial product/ its comparator and contributed to the evaluation "as treated". A TEAE was defined as an event recorded from the first day of exposure to trial product and no later than post-treatment follow-up visit (7 days). Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	4.4% 17/386 • Number of events 22 • Until 52 weeks (26+26) weeks of treatment + 7 days followup for faster aspart (meal) and NovoRapid®(meal) or until 26 weeks of treatment + 7 days followup for faster aspart (post) + 30 day follow-up period for cardio-vascular related events. The safety analysis set included all subjects receiving at least one dose of trial product/ its comparator and contributed to the evaluation "as treated". A TEAE was defined as an event recorded from the first day of exposure to trial product and no later than post-treatment follow-up visit (7 days). Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).	4.2% 16/377 • Number of events 21 • Until 52 weeks (26+26) weeks of treatment + 7 days followup for faster aspart (meal) and NovoRapid®(meal) or until 26 weeks of treatment + 7 days followup for faster aspart (post) + 30 day follow-up period for cardio-vascular related events. The safety analysis set included all subjects receiving at least one dose of trial product/ its comparator and contributed to the evaluation "as treated". A TEAE was defined as an event recorded from the first day of exposure to trial product and no later than post-treatment follow-up visit (7 days). Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).	6.1% 23/380 • Number of events 30 • Until 52 weeks (26+26) weeks of treatment + 7 days followup for faster aspart (meal) and NovoRapid®(meal) or until 26 weeks of treatment + 7 days followup for faster aspart (post) + 30 day follow-up period for cardio-vascular related events. The safety analysis set included all subjects receiving at least one dose of trial product/ its comparator and contributed to the evaluation "as treated". A TEAE was defined as an event recorded from the first day of exposure to trial product and no later than post-treatment follow-up visit (7 days). Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).
Infections and infestations Sinusitis	4.9% 19/386 • Number of events 21 • Until 52 weeks (26+26) weeks of treatment + 7 days followup for faster aspart (meal) and NovoRapid®(meal) or until 26 weeks of treatment + 7 days followup for faster aspart (post) + 30 day follow-up period for cardio-vascular related events. The safety analysis set included all subjects receiving at least one dose of trial product/ its comparator and contributed to the evaluation "as treated". A TEAE was defined as an event recorded from the first day of exposure to trial product and no later than post-treatment follow-up visit (7 days). Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).	1.9% 7/377 • Number of events 7 • Until 52 weeks (26+26) weeks of treatment + 7 days followup for faster aspart (meal) and NovoRapid®(meal) or until 26 weeks of treatment + 7 days followup for faster aspart (post) + 30 day follow-up period for cardio-vascular related events. The safety analysis set included all subjects receiving at least one dose of trial product/ its comparator and contributed to the evaluation "as treated". A TEAE was defined as an event recorded from the first day of exposure to trial product and no later than post-treatment follow-up visit (7 days). Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).	7.4% 28/380 • Number of events 37 • Until 52 weeks (26+26) weeks of treatment + 7 days followup for faster aspart (meal) and NovoRapid®(meal) or until 26 weeks of treatment + 7 days followup for faster aspart (post) + 30 day follow-up period for cardio-vascular related events. The safety analysis set included all subjects receiving at least one dose of trial product/ its comparator and contributed to the evaluation "as treated". A TEAE was defined as an event recorded from the first day of exposure to trial product and no later than post-treatment follow-up visit (7 days). Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).
Infections and infestations Upper respiratory tract infection	14.5% 56/386 • Number of events 75 • Until 52 weeks (26+26) weeks of treatment + 7 days followup for faster aspart (meal) and NovoRapid®(meal) or until 26 weeks of treatment + 7 days followup for faster aspart (post) + 30 day follow-up period for cardio-vascular related events. The safety analysis set included all subjects receiving at least one dose of trial product/ its comparator and contributed to the evaluation "as treated". A TEAE was defined as an event recorded from the first day of exposure to trial product and no later than post-treatment follow-up visit (7 days). Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).	7.4% 28/377 • Number of events 31 • Until 52 weeks (26+26) weeks of treatment + 7 days followup for faster aspart (meal) and NovoRapid®(meal) or until 26 weeks of treatment + 7 days followup for faster aspart (post) + 30 day follow-up period for cardio-vascular related events. The safety analysis set included all subjects receiving at least one dose of trial product/ its comparator and contributed to the evaluation "as treated". A TEAE was defined as an event recorded from the first day of exposure to trial product and no later than post-treatment follow-up visit (7 days). Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).	10.5% 40/380 • Number of events 61 • Until 52 weeks (26+26) weeks of treatment + 7 days followup for faster aspart (meal) and NovoRapid®(meal) or until 26 weeks of treatment + 7 days followup for faster aspart (post) + 30 day follow-up period for cardio-vascular related events. The safety analysis set included all subjects receiving at least one dose of trial product/ its comparator and contributed to the evaluation "as treated". A TEAE was defined as an event recorded from the first day of exposure to trial product and no later than post-treatment follow-up visit (7 days). Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).
Infections and infestations Urinary tract infection	5.2% 20/386 • Number of events 25 • Until 52 weeks (26+26) weeks of treatment + 7 days followup for faster aspart (meal) and NovoRapid®(meal) or until 26 weeks of treatment + 7 days followup for faster aspart (post) + 30 day follow-up period for cardio-vascular related events. The safety analysis set included all subjects receiving at least one dose of trial product/ its comparator and contributed to the evaluation "as treated". A TEAE was defined as an event recorded from the first day of exposure to trial product and no later than post-treatment follow-up visit (7 days). Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).	4.0% 15/377 • Number of events 20 • Until 52 weeks (26+26) weeks of treatment + 7 days followup for faster aspart (meal) and NovoRapid®(meal) or until 26 weeks of treatment + 7 days followup for faster aspart (post) + 30 day follow-up period for cardio-vascular related events. The safety analysis set included all subjects receiving at least one dose of trial product/ its comparator and contributed to the evaluation "as treated". A TEAE was defined as an event recorded from the first day of exposure to trial product and no later than post-treatment follow-up visit (7 days). Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).	4.7% 18/380 • Number of events 29 • Until 52 weeks (26+26) weeks of treatment + 7 days followup for faster aspart (meal) and NovoRapid®(meal) or until 26 weeks of treatment + 7 days followup for faster aspart (post) + 30 day follow-up period for cardio-vascular related events. The safety analysis set included all subjects receiving at least one dose of trial product/ its comparator and contributed to the evaluation "as treated". A TEAE was defined as an event recorded from the first day of exposure to trial product and no later than post-treatment follow-up visit (7 days). Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).
Gastrointestinal disorders Vomiting	4.9% 19/386 • Number of events 23 • Until 52 weeks (26+26) weeks of treatment + 7 days followup for faster aspart (meal) and NovoRapid®(meal) or until 26 weeks of treatment + 7 days followup for faster aspart (post) + 30 day follow-up period for cardio-vascular related events. The safety analysis set included all subjects receiving at least one dose of trial product/ its comparator and contributed to the evaluation "as treated". A TEAE was defined as an event recorded from the first day of exposure to trial product and no later than post-treatment follow-up visit (7 days). Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).	4.0% 15/377 • Number of events 16 • Until 52 weeks (26+26) weeks of treatment + 7 days followup for faster aspart (meal) and NovoRapid®(meal) or until 26 weeks of treatment + 7 days followup for faster aspart (post) + 30 day follow-up period for cardio-vascular related events. The safety analysis set included all subjects receiving at least one dose of trial product/ its comparator and contributed to the evaluation "as treated". A TEAE was defined as an event recorded from the first day of exposure to trial product and no later than post-treatment follow-up visit (7 days). Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).	6.6% 25/380 • Number of events 30 • Until 52 weeks (26+26) weeks of treatment + 7 days followup for faster aspart (meal) and NovoRapid®(meal) or until 26 weeks of treatment + 7 days followup for faster aspart (post) + 30 day follow-up period for cardio-vascular related events. The safety analysis set included all subjects receiving at least one dose of trial product/ its comparator and contributed to the evaluation "as treated". A TEAE was defined as an event recorded from the first day of exposure to trial product and no later than post-treatment follow-up visit (7 days). Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).
Injury, poisoning and procedural complications Wrong drug administered	5.7% 22/386 • Number of events 31 • Until 52 weeks (26+26) weeks of treatment + 7 days followup for faster aspart (meal) and NovoRapid®(meal) or until 26 weeks of treatment + 7 days followup for faster aspart (post) + 30 day follow-up period for cardio-vascular related events. The safety analysis set included all subjects receiving at least one dose of trial product/ its comparator and contributed to the evaluation "as treated". A TEAE was defined as an event recorded from the first day of exposure to trial product and no later than post-treatment follow-up visit (7 days). Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).	4.8% 18/377 • Number of events 20 • Until 52 weeks (26+26) weeks of treatment + 7 days followup for faster aspart (meal) and NovoRapid®(meal) or until 26 weeks of treatment + 7 days followup for faster aspart (post) + 30 day follow-up period for cardio-vascular related events. The safety analysis set included all subjects receiving at least one dose of trial product/ its comparator and contributed to the evaluation "as treated". A TEAE was defined as an event recorded from the first day of exposure to trial product and no later than post-treatment follow-up visit (7 days). Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).	6.1% 23/380 • Number of events 28 • Until 52 weeks (26+26) weeks of treatment + 7 days followup for faster aspart (meal) and NovoRapid®(meal) or until 26 weeks of treatment + 7 days followup for faster aspart (post) + 30 day follow-up period for cardio-vascular related events. The safety analysis set included all subjects receiving at least one dose of trial product/ its comparator and contributed to the evaluation "as treated". A TEAE was defined as an event recorded from the first day of exposure to trial product and no later than post-treatment follow-up visit (7 days). Five (5) subjects randomised to the faster aspart (post) group have consistently taken their bolus insulin before meals throughout the trial and are handled as treated with faster aspart (meal).

Additional Information

Global Clinical Registry (GCR, 1452)

Novo Nordisk A/S

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee At the end of the trial, one or more manuscripts for publication will be prepared collaboratively between Investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for less than 60 days to protect intellectual property.
Publication restrictions are in place

Restriction type: OTHER