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

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01831765
• Collaborator: (none)
• Enrollment: 1,290
• Locations: 191
• Arms: 3
• Actual Duration (Months): 21.5
• Patients Per Site: 6.8
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This trial is conducted in Europe and the United States of America (USA). The aim of the trial is to investigate efficacy and safety of FIAsp (faster-acting insulin aspart) compared to insulin aspart, both in combination with insulin detemir in adults with type 1 diabetes. This trial consists of two periods: a 26 week treatment period followed by a 26 week additional treatment period.

Condition or Disease	Intervention/Treatment	Phase
Diabetes; Diabetes Mellitus, Type 1	Drug: Faster-acting insulin aspart; Drug: insulin detemir; Drug: insulin aspart; Drug: Faster-acting insulin aspart	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1290 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of FIAsp Compared to Insulin Aspart Both in Combination With Insulin Detemir in Adults With Type 1 Diabetes
• Actual Study Start Date: Aug 26, 2013
• Actual Primary Completion Date: May 12, 2015
• Actual Study Completion Date: Jun 11, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Meal time FIAsp and insulin detemir	Drug: Faster-acting insulin aspart; Injected subcutaneously (s.c., under the skin), dose individually adjusted. Meal time dosing is defined as injecting 0-2 minutes before the meal.; Drug: insulin detemir; Injected subcutaneously (s.c., under the skin), dose individually adjusted. Administrated once or twice daily.
Active Comparator: Meal time insulin aspart and insulin detemir	Drug: insulin detemir; Injected subcutaneously (s.c., under the skin), dose individually adjusted. Administrated once or twice daily.; Drug: insulin aspart; Injected subcutaneously (s.c., under the skin), dose individually adjusted.
Experimental: Post meal FIAsp and insulin detemir	Drug: insulin detemir; Injected subcutaneously (s.c., under the skin), dose individually adjusted. Administrated once or twice daily.; Drug: Faster-acting insulin aspart; Injected subcutaneously (s.c., under the skin), dose individually adjusted. Post meal time dosing is defined as injecting 20 minutes after the start of the meal.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in HbA1c (Glycosylated Haemoglobin) [Week 0, week 26]

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

Secondary Outcome Measures

1. Change From Baseline in 2-hour PPG (Postprandial Glucose) Increment (Meal Test) [Week 0, week 26]

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

2. Change From Baseline in HbA1c (Post Meal Arm) [Week 0, week 26]

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

3. Number of Treatment Emergent Confirmed Hypoglycaemic Episodes [From baseline until week 26]

   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.

4. Change From Baseline in Body Weight [Week 0, week 26]

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

5. Frequency of Adverse Events [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.

6. Change in HbA1c [Week 0, week 52]

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

7. Change in PPG (Postprandial Glucose) [Week 0, week 52]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria: - Type 1 diabetes (diagnosed clinically) for 12 months or longer at the time of screening (Visit 1) - Currently treated with a basal-bolus insulin regimen for at least 12 months prior to screening (Visit 1) - Currently treated with a basal insulin analogue (any regimen of insulin detemir or insulin glargine) for at least 4 months prior to screening (Visit 1) - HbA1c 7.0-9.5% (53-80 mmol/mol) (both inclusive) as assessed by central laboratory - Body Mass Index (BMI) below or equal to 35.0 kg/m^2 Exclusion Criteria: - Use of any anti-diabetic drug other than insulin within the last 3 months prior to screening (Visit 1) - Recurrent severe hypoglycaemia (more than one severe hypoglycaemic event during the last 12 months) or hypoglycaemic unawareness as judged by the Investigator, or hospitalisation for diabetic ketoacidosis during the previous 6 months prior to screening (Visit 1) - Cardiovascular disease, within the last 6 months prior to screening (Visit 1), defined as stroke, decompensated heart failure New York Heart Association (NYHA) class III or IV, myocardial infarction, unstable angina pectoris, coronary arterial bypass graft or angioplasty

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Mobile	Alabama	United States	36608
2	Novo Nordisk Investigational Site	Tucson	Arizona	United States	85714
3	Novo Nordisk Investigational Site	Tucson	Arizona	United States	85724
4	Novo Nordisk Investigational Site	Anaheim	California	United States	92801
5	Novo Nordisk Investigational Site	Concord	California	United States	94520
6	Novo Nordisk Investigational Site	Escondido	California	United States	92025
7	Novo Nordisk Investigational Site	Fresno	California	United States	93720
8	Novo Nordisk Investigational Site	Fullerton	California	United States	92835
9	Novo Nordisk Investigational Site	Inglewood	California	United States	90301
10	Novo Nordisk Investigational Site	La Jolla	California	United States	92037
11	Novo Nordisk Investigational Site	La Mesa	California	United States	91942
12	Novo Nordisk Investigational Site	Long Beach	California	United States	90807
13	Novo Nordisk Investigational Site	North Hollywood	California	United States	91606
14	Novo Nordisk Investigational Site	Northridge	California	United States	91324
15	Novo Nordisk Investigational Site	Poway	California	United States	92064
16	Novo Nordisk Investigational Site	San Diego	California	United States	92037
17	Novo Nordisk Investigational Site	Santa Barbara	California	United States	93105-4321
18	Novo Nordisk Investigational Site	Santa Barbara	California	United States	93105
19	Novo Nordisk Investigational Site	Ventura	California	United States	93003-2824
20	Novo Nordisk Investigational Site	Ventura	California	United States	93003
21	Novo Nordisk Investigational Site	Walnut Creek	California	United States	94598
22	Novo Nordisk Investigational Site	Denver	Colorado	United States	80209
23	Novo Nordisk Investigational Site	Newark	Delaware	United States	19713
24	Novo Nordisk Investigational Site	Boca Raton	Florida	United States	33433
25	Novo Nordisk Investigational Site	Coral Gables	Florida	United States	33134
26	Novo Nordisk Investigational Site	Fleming Island	Florida	United States	32203
27	Novo Nordisk Investigational Site	Fort Lauderdale	Florida	United States	33308
28	Novo Nordisk Investigational Site	Fort Lauderdale	Florida	United States	33312
29	Novo Nordisk Investigational Site	Jacksonville	Florida	United States	32204
30	Novo Nordisk Investigational Site	Miami	Florida	United States	33015
31	Novo Nordisk Investigational Site	Miami	Florida	United States	33136
32	Novo Nordisk Investigational Site	Miami	Florida	United States	33156
33	Novo Nordisk Investigational Site	Miami	Florida	United States	33173
34	Novo Nordisk Investigational Site	Miami	Florida	United States	33174
35	Novo Nordisk Investigational Site	Sanford	Florida	United States	32771
36	Novo Nordisk Investigational Site	Tampa	Florida	United States	33614
37	Novo Nordisk Investigational Site	Atlanta	Georgia	United States	30318
38	Novo Nordisk Investigational Site	Atlanta	Georgia	United States	30339
39	Novo Nordisk Investigational Site	Dunwoody	Georgia	United States	30338
40	Novo Nordisk Investigational Site	Lawrenceville	Georgia	United States	30046
41	Novo Nordisk Investigational Site	Roswell	Georgia	United States	30076
42	Novo Nordisk Investigational Site	Honolulu	Hawaii	United States	96814
43	Novo Nordisk Investigational Site	Idaho Falls	Idaho	United States	83404-7596
44	Novo Nordisk Investigational Site	Nampa	Idaho	United States	83686-6011
45	Novo Nordisk Investigational Site	Chicago	Illinois	United States	60064
46	Novo Nordisk Investigational Site	Chicago	Illinois	United States	60607
47	Novo Nordisk Investigational Site	Crystal Lake	Illinois	United States	60012
48	Novo Nordisk Investigational Site	Springfield	Illinois	United States	62711
49	Novo Nordisk Investigational Site	Muncie	Indiana	United States	47304
50	Novo Nordisk Investigational Site	Lenexa	Kansas	United States	66219
51	Novo Nordisk Investigational Site	Topeka	Kansas	United States	66606
52	Novo Nordisk Investigational Site	Lexington	Kentucky	United States	40502
53	Novo Nordisk Investigational Site	Lexington	Kentucky	United States	40503
54	Novo Nordisk Investigational Site	Portland	Maine	United States	04101
55	Novo Nordisk Investigational Site	Baltimore	Maryland	United States	21204
56	Novo Nordisk Investigational Site	Baltimore	Maryland	United States	21287
57	Novo Nordisk Investigational Site	Hyattsville	Maryland	United States	20782
58	Novo Nordisk Investigational Site	Rockville	Maryland	United States	20852
59	Novo Nordisk Investigational Site	Waltham	Massachusetts	United States	02453
60	Novo Nordisk Investigational Site	Worcester	Massachusetts	United States	01655
61	Novo Nordisk Investigational Site	Kalamazoo	Michigan	United States	49048
62	Novo Nordisk Investigational Site	Eagan	Minnesota	United States	55123
63	Novo Nordisk Investigational Site	Minneapolis	Minnesota	United States	55416
64	Novo Nordisk Investigational Site	Kansas City	Missouri	United States	64106
65	Novo Nordisk Investigational Site	Springfield	Missouri	United States	65807
66	Novo Nordisk Investigational Site	Butte	Montana	United States	59701
67	Novo Nordisk Investigational Site	Omaha	Nebraska	United States	68114
68	Novo Nordisk Investigational Site	Henderson	Nevada	United States	89052-2649
69	Novo Nordisk Investigational Site	Las Vegas	Nevada	United States	89128
70	Novo Nordisk Investigational Site	Las Vegas	Nevada	United States	89148
71	Novo Nordisk Investigational Site	Nashua	New Hampshire	United States	03063
72	Novo Nordisk Investigational Site	Hoboken	New Jersey	United States	07030
73	Novo Nordisk Investigational Site	Jersey City	New Jersey	United States	07306
74	Novo Nordisk Investigational Site	Lawrenceville	New Jersey	United States	08648
75	Novo Nordisk Investigational Site	Albuquerque	New Mexico	United States	87106
76	Novo Nordisk Investigational Site	Albuquerque	New Mexico	United States	87109-2134
77	Novo Nordisk Investigational Site	Albuquerque	New Mexico	United States	87131
78	Novo Nordisk Investigational Site	Albany	New York	United States	12206
79	Novo Nordisk Investigational Site	New York	New York	United States	10029
80	Novo Nordisk Investigational Site	Rochester	New York	United States	14607
81	Novo Nordisk Investigational Site	Smithtown	New York	United States	11787
82	Novo Nordisk Investigational Site	Staten Island	New York	United States	10301-3901
83	Novo Nordisk Investigational Site	Staten Island	New York	United States	10301
84	Novo Nordisk Investigational Site	Chapel Hill	North Carolina	United States	27517
85	Novo Nordisk Investigational Site	Greenville	North Carolina	United States	27834
86	Novo Nordisk Investigational Site	Morehead City	North Carolina	United States	28557
87	Novo Nordisk Investigational Site	Columbus	Ohio	United States	43201
88	Novo Nordisk Investigational Site	Mentor	Ohio	United States	44060
89	Novo Nordisk Investigational Site	Portland	Oregon	United States	97210
90	Novo Nordisk Investigational Site	Portland	Oregon	United States	97239
91	Novo Nordisk Investigational Site	Jenkintown	Pennsylvania	United States	19046-3638
92	Novo Nordisk Investigational Site	Philadelphia	Pennsylvania	United States	19140-5103
93	Novo Nordisk Investigational Site	Philadelphia	Pennsylvania	United States	19140
94	Novo Nordisk Investigational Site	Greenville	South Carolina	United States	29605-4254
95	Novo Nordisk Investigational Site	Chattanooga	Tennessee	United States	37411
96	Novo Nordisk Investigational Site	Amarillo	Texas	United States	79106
97	Novo Nordisk Investigational Site	Austin	Texas	United States	78731
98	Novo Nordisk Investigational Site	Beaumont	Texas	United States	77701
99	Novo Nordisk Investigational Site	Dallas	Texas	United States	75230
100	Novo Nordisk Investigational Site	Dallas	Texas	United States	75231
101	Novo Nordisk Investigational Site	Dallas	Texas	United States	75246
102	Novo Nordisk Investigational Site	Dallas	Texas	United States	75390-9302
103	Novo Nordisk Investigational Site	Houston	Texas	United States	77079
104	Novo Nordisk Investigational Site	Houston	Texas	United States	77099
105	Novo Nordisk Investigational Site	Lubbock	Texas	United States	79423
106	Novo Nordisk Investigational Site	Plano	Texas	United States	75093
107	Novo Nordisk Investigational Site	Round Rock	Texas	United States	78681
108	Novo Nordisk Investigational Site	Sugar Land	Texas	United States	77479
109	Novo Nordisk Investigational Site	Magna	Utah	United States	84044
110	Novo Nordisk Investigational Site	Olympia	Washington	United States	98502
111	Novo Nordisk Investigational Site	Renton	Washington	United States	98057
112	Novo Nordisk Investigational Site	Spokane	Washington	United States	99201
113	Novo Nordisk Investigational Site	Spokane	Washington	United States	99202-1334
114	Novo Nordisk Investigational Site	Spokane	Washington	United States	99202-3649
115	Novo Nordisk Investigational Site	Spokane	Washington	United States	99202
116	Novo Nordisk Investigational Site	Spokane	Washington	United States	99208
117	Novo Nordisk Investigational Site	Bonheiden		Belgium	2820
118	Novo Nordisk Investigational Site	Brussels		Belgium	1070
119	Novo Nordisk Investigational Site	Edegem		Belgium	2650
120	Novo Nordisk Investigational Site	Gent		Belgium	9000
121	Novo Nordisk Investigational Site	Leuven		Belgium	3000
122	Novo Nordisk Investigational Site	Edmonton	Alberta	Canada	T5J 3N4
123	Novo Nordisk Investigational Site	Edmonton	Alberta	Canada	T6G 2E1
124	Novo Nordisk Investigational Site	Victoria	British Columbia	Canada	V8R 1J8
125	Novo Nordisk Investigational Site	Winnipeg	Manitoba	Canada	R3E 3P4
126	Novo Nordisk Investigational Site	Hamilton	Ontario	Canada	L8N 3Z5
127	Novo Nordisk Investigational Site	London	Ontario	Canada	N6A 4V2
128	Novo Nordisk Investigational Site	London	Ontario	Canada	N6G 2M1
129	Novo Nordisk Investigational Site	Mississauga	Ontario	Canada	L5M 2V8
130	Novo Nordisk Investigational Site	Toronto	Ontario	Canada	M5T 3L9
131	Novo Nordisk Investigational Site	Montreal	Quebec	Canada	H2W 1R7
132	Novo Nordisk Investigational Site	Sherbrooke	Quebec	Canada	J1G 5K2
133	Novo Nordisk Investigational Site	Quebec		Canada	G1V 4G2
134	Novo Nordisk Investigational Site	Brno		Czechia	65691
135	Novo Nordisk Investigational Site	Hradec Kralove		Czechia	50005
136	Novo Nordisk Investigational Site	Prague 4		Czechia	140 21
137	Novo Nordisk Investigational Site	Praha 10		Czechia	100 00
138	Novo Nordisk Investigational Site	Praha		Czechia	12808
139	Novo Nordisk Investigational Site	Helsinki		Finland	00260
140	Novo Nordisk Investigational Site	Kerava		Finland	FI-04200
141	Novo Nordisk Investigational Site	Lappeenranta		Finland	53130
142	Novo Nordisk Investigational Site	Raisio		Finland	21200
143	Novo Nordisk Investigational Site	Tampere		Finland	33900
144	Novo Nordisk Investigational Site	Turku		Finland	FI-20100
145	Novo Nordisk Investigational Site	Bad Mergentheim		Germany	97980
146	Novo Nordisk Investigational Site	Berlin		Germany	13597
147	Novo Nordisk Investigational Site	Damme		Germany	49401
148	Novo Nordisk Investigational Site	Dresden		Germany	01219
149	Novo Nordisk Investigational Site	Dresden		Germany	01307
150	Novo Nordisk Investigational Site	Elsterwerda		Germany	04910
151	Novo Nordisk Investigational Site	Falkensee		Germany	14612
152	Novo Nordisk Investigational Site	Friedrichsthal		Germany	66299
153	Novo Nordisk Investigational Site	Fulda		Germany	36037
154	Novo Nordisk Investigational Site	Hamburg		Germany	22607
155	Novo Nordisk Investigational Site	Hohenmölsen		Germany	06679
156	Novo Nordisk Investigational Site	Lingen		Germany	49808
157	Novo Nordisk Investigational Site	Ludwigshafen		Germany	67059
158	Novo Nordisk Investigational Site	Münster		Germany	48143
159	Novo Nordisk Investigational Site	Münster		Germany	48145
160	Novo Nordisk Investigational Site	Neuwied		Germany	56564
161	Novo Nordisk Investigational Site	Oldenburg		Germany	23758
162	Novo Nordisk Investigational Site	Rehburg-Loccum		Germany	31547
163	Novo Nordisk Investigational Site	Rehlingen-Siersburg		Germany	66780
164	Novo Nordisk Investigational Site	Rostock		Germany	18057
165	Novo Nordisk Investigational Site	Saint Ingbert-Oberwürzbach		Germany	66386
166	Novo Nordisk Investigational Site	Schweinfurt		Germany	97421
167	Novo Nordisk Investigational Site	Völklingen		Germany	66333
168	Novo Nordisk Investigational Site	Wangen		Germany	88239
169	Novo Nordisk Investigational Site	Zwenkau		Germany	04442
170	Novo Nordisk Investigational Site	Budapest		Hungary	1076
171	Novo Nordisk Investigational Site	Budapest		Hungary	1089
172	Novo Nordisk Investigational Site	Debrecen		Hungary	4043
173	Novo Nordisk Investigational Site	Kaposvár		Hungary	7400
174	Novo Nordisk Investigational Site	Szeged		Hungary	H-6720
175	Novo Nordisk Investigational Site	Szombathely		Hungary	H-9700
176	Novo Nordisk Investigational Site	Bialystok		Poland	15-435
177	Novo Nordisk Investigational Site	Gdansk		Poland	80-858
178	Novo Nordisk Investigational Site	Krakow		Poland	31-261
179	Novo Nordisk Investigational Site	Lublin		Poland	20-538
180	Novo Nordisk Investigational Site	Szczecin		Poland	70-376
181	Novo Nordisk Investigational Site	Warszawa		Poland	02-507
182	Novo Nordisk Investigational Site	Bath		United Kingdom	BA1 3NG
183	Novo Nordisk Investigational Site	Gillingham		United Kingdom	ME7 5NY
184	Novo Nordisk Investigational Site	Glasgow		United Kingdom	G21 3UW
185	Novo Nordisk Investigational Site	Guildford		United Kingdom	GU2 7XX
186	Novo Nordisk Investigational Site	Inverness		United Kingdom	IV2 3JH
187	Novo Nordisk Investigational Site	Inverness		United Kingdom	IV2 3UJ
188	Novo Nordisk Investigational Site	Ipswich		United Kingdom	IP4 5PD
189	Novo Nordisk Investigational Site	Nottingham		United Kingdom	NG7 2UH
190	Novo Nordisk Investigational Site	Portsmouth		United Kingdom	PO6 3LY
191	Novo Nordisk Investigational Site	Sheffield		United Kingdom	S5 7AU

Sponsors and Collaborators

• Novo Nordisk A/S

Investigators

• Study Director: Global Clinical Registry (GCR, 1452), Novo Nordisk A/S

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Clinical Trials at Novo Nordisk

Publications

• Rose L, Kadowaki T, Pieber TR, Buchholtz K, Ekelund M, Gorst-Rasmussen A, Philis-Tsimikas A. Efficacy and Safety of Fast-Acting Insulin Aspart in People with Type 1 Diabetes Using Carbohydrate Counting: A Post Hoc Analysis of Two Randomised Controlled Trials. Diabetes Ther. 2019 Jun;10(3):1029-1041. doi: 10.1007/s13300-019-0608-4. Epub 2019 Apr 4.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT01831765
• Other Study ID Numbers: NN1218-3852; 2010-024049-53; U1111-1118-2442
• First Posted: Apr 15, 2013
• Last Update Posted: Jun 12, 2019
• Last Verified: May 1, 2019

• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1; Insulin; Insulin, Globin Zinc; Insulin Aspart; Insulin, Long-Acting; Insulin degludec, insulin aspart drug combination; Insulin Detemir

Study Results

Participant Flow

Recruitment Details	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.
Pre-assignment Detail	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.

Arm/Group Title	Faster Aspart (Meal)	Faster Aspart (Post)	NovoRapid (Meal)
Arm/Group Description	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.	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.	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.
Period Title: Overall Study
STARTED	381	382	380
Completed 26 Weeks	351	355	356
Completed 52 Weeks	337	0	338
COMPLETED	337	355	338
NOT COMPLETED	44	27	42

Baseline Characteristics

Arm/Group Title	Faster Aspart (Meal)	Faster Aspart (Post)	NovoRapid (Meal)	Total
Arm/Group Description	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.	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.	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 of all reporting groups
Overall Participants	381	382	380	1143
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	46.1 (13.8)	43.5 (13.7)	43.7 (14)	44.4 (13.9)
Age, Customized (Count of Participants)
Adults (18-64 years)	346 90.8%	359 94%	352 92.6%	1057 92.5%
From 65-85 years	35 9.2%	23 6%	28 7.4%	86 7.5%
Sex: Female, Male (Count of Participants)
Female	166 43.6%	163 42.7%	142 37.4%	471 41.2%
Male	215 56.4%	219 57.3%	238 62.6%	672 58.8%
Body Weight (Kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Kg]	78.56 (14.89)	80.49 (15.93)	80.15 (15.21)	79.73 (15.36)
Glycosylated haemoglobin (HbA1c) (Percentage of glycosylated haemoglobin) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percentage of glycosylated haemoglobin]	7.62 (0.71)	7.63 (0.72)	7.58 (0.68)	7.61 (0.70)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in HbA1c (Glycosylated Haemoglobin)
Description	Change from baseline in HbA1c after 26 weeks of randomised treatment.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Faster Aspart (Meal)	Faster Aspart (Post)	NovoRapid (Meal)
Arm/Group Description	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.	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.	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.
Measure Participants	381	382	380
Week 0 (Baseline)	7.62 (0.71)	7.63 (0.72)	7.58 (0.68)
Week 26	7.31 (0.77)	7.51 (0.77)	7.42 (0.78)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Faster Aspart (Meal), NovoRapid (Meal)
	Comments	Change from baseline in HbA1c analysed using a mixed effect model for repeated measurements including visit 14, 18, 22, 26, 30, 34 and 36. The model included treatment, region and strata (combination of bolus adjusting method, basal treatment regimen and continuous glucose monitoring (CGM) and frequently sampled meal test subgroup) as fixed effects, subject as random effect, baseline HbA1c as covariate and interaction between all fixed effects and visit, and between the covariate and visit.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The assessment was done by comparing the difference of faster aspart vs. NovoRapid®/NovoLog® in change from baseline in HbA1c after 26 weeks of randomised treatment to a non-inferiority limit of 0.4%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.15
	Confidence Interval	(2-Sided) 95%; -0.23 to -0.07
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Faster Aspart (Post), NovoRapid (Meal)
	Comments	Change from baseline in HbA1c analysed using a mixedeffect model for repeated measurements including visit 14, 18, 22, 26, 30, 34 and 36. The model included treatment, region and strata (combination of bolus adjusting method, basal treatment regimen and continuous glucose monitoring (CGM) and frequently sampled meal test subgroup) as fixed effects, subject as random effect, baseline HbA1c as covariate and interaction between all fixed effects and visit, and between the covariate and visit.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The assessment was done by comparing the difference of faster aspart vs. NovoRapid®/NovoLog® in change from baseline in HbA1c after 26 weeks of randomised treatment to a non-inferiority limit of 0.4%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.04
	Confidence Interval	(2-Sided) 95%; -0.04 to 0.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in 2-hour PPG (Postprandial Glucose) Increment (Meal Test)
Description	Change from baseline in 2-hour PPG increments after 26 weeks of randomised treatment (meal test).
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Faster Aspart (Meal)	Faster Aspart (Post)	NovoRapid (Meal)
Arm/Group Description	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.	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.	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.
Measure Participants	381	382	380
Week 0: Baseline	6.06 (5.16)	6.06 (4.9)	6.24 (4.81)
Week 26	5.88 (4.67)	6.73 (4.67)	6.55 (4.78)

3. Secondary Outcome

Title	Change From Baseline in HbA1c (Post Meal Arm)
Description	Change from baseline in HbA1c (post meal arm) after 26 weeks of randomised treatment.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Faster Aspart (Post)	NovoRapid (Meal)
Arm/Group Description	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.	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.
Measure Participants	382	380
Week 0 (baseline)	7.63 (0.72)	7.58 (0.68)
Week 26	7.51 (0.77)	7.42 (0.78)

4. Secondary Outcome

Title	Number of Treatment Emergent Confirmed Hypoglycaemic Episodes
Description	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.
Time Frame	From baseline until week 26

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Faster Aspart (Meal)	Faster Aspart (Post)	NovoRapid (Meal)
Arm/Group Description	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.	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.	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.
Measure Participants	386	377	380
Number [event rate/100 patient yrs of exposure]	5899	5443	5865

5. Secondary Outcome

Title	Change From Baseline in Body Weight
Description	Change from baseline in body weight after 26 weeks of randomised treatment.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Faster Aspart (Meal)	Faster Aspart (Post)	NovoRapid (Meal)
Arm/Group Description	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.	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.	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.
Measure Participants	381	382	380
Week 0: Baseline	78.56 (14.89)	80.49 (15.93)	80.15 (15.21)
Week 26	79.21 (15.25)	81.17 (16.45)	80.69 (15.44)

6. Secondary Outcome

Title	Frequency of Adverse Events
Description	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.
Time Frame	After 52 weeks of randomised treatment

Outcome Measure Data

Analysis Population Description

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).

Arm/Group Title	Faster Aspart (Meal)	Faster Aspart (Post)	NovoRapid (Meal)
Arm/Group Description	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.	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.	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.
Measure Participants	386	377	380
Number [event /100 patient yrs of exposure]	445.8	441	411

7. Secondary Outcome

Title	Change in HbA1c
Description	Change from baseline in HbA1c (%) after 52 weeks of randomised treatment.
Time Frame	Week 0, week 52

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Faster Aspart (Meal)	NovoRapid (Meal)
Arm/Group Description	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.	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.
Measure Participants	381	380
Week 0 (baseline)	7.62 (0.71)	7.58 (0.68)
Week 52	7.51 (0.83)	7.58 (0.86)

8. Secondary Outcome

Title	Change in PPG (Postprandial Glucose)
Description	Change from baseline in PPG and PPG increment (meal test) after 52 weeks of randomised treatment.
Time Frame	Week 0, week 52

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Faster Aspart (Meal)	NovoRapid (Meal)
Arm/Group Description	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.	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.
Measure Participants	381	380
PPG at 120 minutes (Baseline)	14.51 (6.09)	14.14 (5.69)
PPG at 120 minutes (Week 52)	14.26 (5.76)	14.51 (6.02)
PPG increment at 120 mins (Baseline)	6.06 (5.16)	6.24 (4.81)
PPG increment at 120 mins(Week 52)	5.71 (4.92)	6.14 (4.86)

Adverse Events

Time Frame	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.
Adverse Event Reporting Description	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).
Arm/Group Title	Faster Aspart (Meal)		Faster Aspart (Post)		NovoRapid (Meal)
Arm/Group Description	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.		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.		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.
All Cause Mortality
	Faster Aspart (Meal)		Faster Aspart (Post)		NovoRapid (Meal)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Faster Aspart (Meal)		Faster Aspart (Post)		NovoRapid (Meal)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	35/386 (9.1%)		28/377 (7.4%)		33/380 (8.7%)
Cardiac disorders
Angina pectoris	0/386 (0%)	0	1/377 (0.3%)	1	0/380 (0%)	0
Arrhythmia	0/386 (0%)	0	1/377 (0.3%)	1	0/380 (0%)	0
Arteriosclerosis coronary artery	0/386 (0%)	0	1/377 (0.3%)	1	0/380 (0%)	0
Cardiac failure congestive	1/386 (0.3%)	1	0/377 (0%)	0	0/380 (0%)	0
Cardiac ventricular thrombosis	1/386 (0.3%)	1	0/377 (0%)	0	0/380 (0%)	0
Coronary artery disease	1/386 (0.3%)	1	1/377 (0.3%)	1	0/380 (0%)	0
Myocardial infarction	0/386 (0%)	0	0/377 (0%)	0	1/380 (0.3%)	1
Eye disorders
Diabetic retinopathy	0/386 (0%)	0	0/377 (0%)	0	1/380 (0.3%)	1
Gastrointestinal disorders
Abdominal pain	0/386 (0%)	0	0/377 (0%)	0	1/380 (0.3%)	1
Anal fistula	0/386 (0%)	0	0/377 (0%)	0	1/380 (0.3%)	1
Colitis microscopic	0/386 (0%)	0	0/377 (0%)	0	1/380 (0.3%)	1
Diarrhoea	0/386 (0%)	0	1/377 (0.3%)	1	0/380 (0%)	0
Nausea	0/386 (0%)	0	1/377 (0.3%)	1	0/380 (0%)	0
Pancreatitis	1/386 (0.3%)	1	0/377 (0%)	0	1/380 (0.3%)	1
Peritoneal fibrosis	0/386 (0%)	0	1/377 (0.3%)	1	0/380 (0%)	0
Vomiting	0/386 (0%)	0	1/377 (0.3%)	1	0/380 (0%)	0
Infections and infestations
Appendicitis	1/386 (0.3%)	1	0/377 (0%)	0	0/380 (0%)	0
Bronchitis	0/386 (0%)	0	0/377 (0%)	0	1/380 (0.3%)	1
Cellulitis	0/386 (0%)	0	0/377 (0%)	0	1/380 (0.3%)	1
Gastroenteritis	1/386 (0.3%)	1	0/377 (0%)	0	0/380 (0%)	0
Osteomyelitis	0/386 (0%)	0	1/377 (0.3%)	1	0/380 (0%)	0
Peritonsillar abscess	0/386 (0%)	0	0/377 (0%)	0	1/380 (0.3%)	1
Pharyngitis	0/386 (0%)	0	0/377 (0%)	0	1/380 (0.3%)	1
Pilonidal cyst	0/386 (0%)	0	1/377 (0.3%)	1	0/380 (0%)	0
Pneumonia staphylococcal	0/386 (0%)	0	1/377 (0.3%)	1	0/380 (0%)	0
Pyelonephritis	1/386 (0.3%)	1	1/377 (0.3%)	1	0/380 (0%)	0
Vestibular neuronitis	1/386 (0.3%)	1	0/377 (0%)	0	0/380 (0%)	0
Viral infection	0/386 (0%)	0	0/377 (0%)	0	1/380 (0.3%)	1
Injury, poisoning and procedural complications
Ankle fracture	1/386 (0.3%)	1	1/377 (0.3%)	1	0/380 (0%)	0
Fall	2/386 (0.5%)	2	0/377 (0%)	0	0/380 (0%)	0
Lower limb fracture	0/386 (0%)	0	1/377 (0.3%)	1	0/380 (0%)	0
Lumbar vertebral fracture	1/386 (0.3%)	1	0/377 (0%)	0	1/380 (0.3%)	1
Overdose	0/386 (0%)	0	1/377 (0.3%)	1	0/380 (0%)	0
Radius fracture	1/386 (0.3%)	1	0/377 (0%)	0	0/380 (0%)	0
Road traffic accident	0/386 (0%)	0	1/377 (0.3%)	1	0/380 (0%)	0
Subdural haematoma	1/386 (0.3%)	1	0/377 (0%)	0	0/380 (0%)	0
Tendon rupture	1/386 (0.3%)	1	0/377 (0%)	0	0/380 (0%)	0
Wrong drug administered	1/386 (0.3%)	1	1/377 (0.3%)	1	0/380 (0%)	0
Investigations
Blood glucose decreased	0/386 (0%)	0	0/377 (0%)	0	1/380 (0.3%)	2
Cardiovascular evaluation	0/386 (0%)	0	0/377 (0%)	0	1/380 (0.3%)	1
Metabolism and nutrition disorders
Diabetic ketoacidosis	1/386 (0.3%)	1	0/377 (0%)	0	2/380 (0.5%)	2
Hypoglycaemia	12/386 (3.1%)	16	11/377 (2.9%)	11	10/380 (2.6%)	10
Lactic acidosis	0/386 (0%)	0	1/377 (0.3%)	1	0/380 (0%)	0
Musculoskeletal and connective tissue disorders
Compartment syndrome	0/386 (0%)	0	0/377 (0%)	0	1/380 (0.3%)	1
Joint stiffness	0/386 (0%)	0	0/377 (0%)	0	1/380 (0.3%)	1
Meniscal degeneration	0/386 (0%)	0	0/377 (0%)	0	1/380 (0.3%)	1
Musculoskeletal pain	0/386 (0%)	0	0/377 (0%)	0	1/380 (0.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon	0/386 (0%)	0	1/377 (0.3%)	1	0/380 (0%)	0
Lung neoplasm malignant	1/386 (0.3%)	1	0/377 (0%)	0	0/380 (0%)	0
Papillary thyroid cancer	0/386 (0%)	0	0/377 (0%)	0	1/380 (0.3%)	1
Nervous system disorders
Carotid artery stenosis	0/386 (0%)	0	1/377 (0.3%)	1	0/380 (0%)	0
Hypoglycaemic seizure	0/386 (0%)	0	1/377 (0.3%)	1	0/380 (0%)	0
Hypoglycaemic unconsciousness	5/386 (1.3%)	8	3/377 (0.8%)	3	4/380 (1.1%)	5
Ischaemic stroke	0/386 (0%)	0	0/377 (0%)	0	1/380 (0.3%)	1
Subarachnoid haemorrhage	1/386 (0.3%)	1	0/377 (0%)	0	0/380 (0%)	0
Transient ischaemic attack	1/386 (0.3%)	1	0/377 (0%)	0	0/380 (0%)	0
Psychiatric disorders
Mental status changes	0/386 (0%)	0	0/377 (0%)	0	1/380 (0.3%)	1
Reproductive system and breast disorders
Uterine polyp	1/386 (0.3%)	1	0/377 (0%)	0	0/380 (0%)	0
Respiratory, thoracic and mediastinal disorders
Nasal septum deviation	1/386 (0.3%)	1	0/377 (0%)	0	0/380 (0%)	0
Surgical and medical procedures
Coronary arterial stent insertion	1/386 (0.3%)	1	0/377 (0%)	0	0/380 (0%)	0
Coronary revascularisation	0/386 (0%)	0	1/377 (0.3%)	1	0/380 (0%)	0
Vascular disorders
Aneurysm	1/386 (0.3%)	1	0/377 (0%)	0	0/380 (0%)	0
Peripheral arterial occlusive disease	1/386 (0.3%)	1	0/377 (0%)	0	0/380 (0%)	0
Thrombosis	1/386 (0.3%)	1	0/377 (0%)	0	0/380 (0%)	0
Other (Not Including Serious) Adverse Events
	Faster Aspart (Meal)		Faster Aspart (Post)		NovoRapid (Meal)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	252/386 (65.3%)		189/377 (50.1%)		236/380 (62.1%)
Gastrointestinal disorders
Diarrhoea	27/386 (7%)	34	11/377 (2.9%)	11	27/380 (7.1%)	33
Nausea	28/386 (7.3%)	36	18/377 (4.8%)	29	23/380 (6.1%)	34
Vomiting	19/386 (4.9%)	23	15/377 (4%)	16	25/380 (6.6%)	30
Infections and infestations
Gastroenteritis	20/386 (5.2%)	25	8/377 (2.1%)	8	17/380 (4.5%)	21
Influenza	22/386 (5.7%)	30	11/377 (2.9%)	12	37/380 (9.7%)	54
Nasopharyngitis	128/386 (33.2%)	214	90/377 (23.9%)	111	120/380 (31.6%)	174
Sinusitis	19/386 (4.9%)	21	7/377 (1.9%)	7	28/380 (7.4%)	37
Upper respiratory tract infection	56/386 (14.5%)	75	28/377 (7.4%)	31	40/380 (10.5%)	61
Urinary tract infection	20/386 (5.2%)	25	15/377 (4%)	20	18/380 (4.7%)	29
Injury, poisoning and procedural complications
Wrong drug administered	22/386 (5.7%)	31	18/377 (4.8%)	20	23/380 (6.1%)	28
Musculoskeletal and connective tissue disorders
Back pain	28/386 (7.3%)	36	15/377 (4%)	17	20/380 (5.3%)	22
Nervous system disorders
Headache	37/386 (9.6%)	70	26/377 (6.9%)	41	45/380 (11.8%)	79
Respiratory, thoracic and mediastinal disorders
Cough	17/386 (4.4%)	21	12/377 (3.2%)	13	20/380 (5.3%)	21
Oropharyngeal pain	17/386 (4.4%)	22	16/377 (4.2%)	21	23/380 (6.1%)	30

Limitations/Caveats

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.