BEGIN™: Comparison of NN1250 With Insulin Glargine Plus Insulin Aspart With/Without Metformin and With/Without Pioglitazone in Type 2 Diabetes

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00972283
• Collaborator: (none)
• Enrollment: 1,006
• Locations: 136
• Arms: 2
• Actual Duration (Months): 13.9
• Patients Per Site: 7.4
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This trial is conducted in Africa, Asia, Europe, and the United States of America (USA).

The aim of this clinical trial is to compare NN1250 (insulin degludec (IDeg)) with insulin glargine (IGlar) plus insulin aspart (IAsp) with/without metformin and with/without pioglitazone in subjects with type 2 diabetes (main period) followed by investigating the long-term safety in terms of comparing NN1250 with insulin glargine plus insulin aspart with or without metformin and with or without pioglitazone in subjects with type 2 diabetes.

All oral anti-diabetic drug (OAD) treatment will be discontinued, if applicable, when trial participant enters the trial (NN1250-3582) with the exception of metformin and pioglitazone.

Subjects who consent to participate in the extension trial (NN1250-3667) will continue to receive the treatment to which they were randomly allocated in the 52 week trial NN1250-3582.

The main period is registered internally at Novo Nordisk as NN1250-3582 while the extension period is registered as NN1250-3667.

Condition or Disease	Intervention/Treatment	Phase
Diabetes; Diabetes Mellitus, Type 2	Drug: insulin degludec; Drug: insulin glargine; Drug: insulin aspart	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1006 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: NN1250-3582: A 52-week Randomised, Controlled, Open Label, Multicentre, Multinational Treat-to-target Trial Comparing Efficacy and Safety of SIBA and Insulin Glargine Both Administered Once Daily in a Basal-bolus Regimen With Insulin Aspart as Mealtime Insulin ± Treatment With Metformin, ± Pioglitazone in Subjects With Type 2 Diabetes Currently Treated With Insulin Qualifying for Intensified Treatment/NN1250-3667: An Extension Trial to NN1250-3582 Comparing Safety and Efficacy of NN1250 and Insulin Glargine, Both With Insulin Aspart as Meal-time Insulin ± OADs in Type 2 Diabetes (BEGIN™: BB)
• Actual Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: Oct 28, 2010
• Actual Study Completion Date: Oct 28, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IDeg OD	Drug: insulin degludec; Injected subcutaneously (under the skin) with main evening meal. Dose was individually adjusted.; Drug: insulin aspart; Injected subcutaneously (under the skin) at each main meal. Dose was individually adjusted.
Active Comparator: IGlar OD	Drug: insulin glargine; Injected subcutanoeusly (under the skin) according to approved label. Dose was individually adjusted.; Drug: insulin aspart; Injected subcutaneously (under the skin) at each main meal. Dose was individually adjusted.

Outcome Measures

Primary Outcome Measures

1. Main Trial (Primary Endpoint): Change in Glycosylated Haemoglobin (HbA1c) After 52 Weeks of Treatment [Week 0, Week 52]

   Change from baseline in HbA1c after 52 weeks of treatment

2. Extension Trial (Primary Endpoint): Rate of Confirmed Hypoglycaemic Episodes [Week 0 to Week 78 + 7 days follow up]

   Rate of confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes are defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes are defined as able to treat her/himself and plasma glucose below 3.1 mmol/L.

3. Extension Trial (Primary Endpoint): Rate of Nocturnal Confirmed Hypoglycaemic Episodes [Week 0 to Week 78 + 7 days follow up]

   Rate of confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes are defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes are defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. Nocturnal hypoglycaemic episodes are defined as occurring between 00:01 and 05:59 a.m.

4. Rate of Treatment Emergent Adverse Events (AEs) [Week 0 to Week 78 + 7 days follow up]

   Corresponds to rate of AEs per 100 patient years of exposure. Mild AEs: no or transient symptoms, no interference with subject's daily activities. Moderate AEs: marked symptoms, moderate interference with subject's daily activities. Severe AEs: considerable interference with subject's daily activities, unacceptable. Serious adverse event (SAE): AE that at any dose results in any of the following: death, a life-threatening experience, in-subject hospitalization/prolongation of existing hospitalisation, persistent/significant disability/incapacity/congenital anomaly/birth defect.

Secondary Outcome Measures

1. Extension Trial (Secondary Endpoint): Change in Glycosylated Haemoglobin (HbA1c) After 78 Weeks of Treatment [Week 0, Week 78]

   Change from baseline in HbA1c after 78 weeks of treatment

2. Main Trial (Secondary Endpoint): Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) at Week 52 [Week 52]

   Mean of 9-point SMPG at 52 weeks of treatment. Plasma glucose measured: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner, bedtime, at 4 am and before breakfast.

3. Extension Trial (Secondary Endpoint): Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) at Week 78 [Week 78]

   Mean of the SMPG at 78 weeks of treatment. Plasma glucose measured: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner, bedtime, at 4 am, before breakfast.

4. Main Trial (Secondary Endpoint): Rate of Confirmed Hypoglycaemic Episodes [Week 0 to Week 52 + 7 days follow up]

   Rate of confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes are defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes are defined as able to treat her/himself and plasma glucose below 3.1 mmol/L.

5. Main Trial (Secondary Endpoint): Rate of Nocturnal Confirmed Hypoglycaemic Episodes [Week 0 to Week 52 + 7 days follow up]

   Rate of confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes are defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes are defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. Nocturnal hypoglycaemic episodes are defined as occurring between 00:01 and 05:59 a.m.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• For MAIN period (NN1250-3582):

• Type 2 diabetes mellitus for at least 6 months

• Ongoing daily treatment with insulin (premix, self-mix, basal only, basal bolus) for at least 3 months with/without oral anti-diabetics drug (OAD) prior to trial start

• HbA1c 7.0-10.0 % (both inclusive)

• Body Mass Index (BMI) below or equal to 40.0 kg/m^2

• For EXTENSION period (NN1250-3667):

• Completion of the 52 week treatment period in NN1250-3582

Exclusion Criteria:

• For MAIN period (NN1250-3582):

• Treatment with other insulin regimens than premix, self-mix, basal only, basal bolus within 3 months

• Cardiovascular disease within the last 6 months

• Uncontrolled treated/untreated severe hypertension

• Pregnancy, breast-feeding, the intention of becoming pregnant or not using adequate contraceptive measures

• Cancer and medical history of cancer

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Alexander City	Alabama	United States	35010
2	Novo Nordisk Investigational Site	Birmingham	Alabama	United States	35209
3	Novo Nordisk Investigational Site	Goodyear	Arizona	United States	85395
4	Novo Nordisk Investigational Site	Peoria	Arizona	United States	85381
5	Novo Nordisk Investigational Site	Anaheim	California	United States	92801
6	Novo Nordisk Investigational Site	Huntington Beach	California	United States	92648
7	Novo Nordisk Investigational Site	Los Gatos	California	United States	95032
8	Novo Nordisk Investigational Site	Salinas	California	United States	93901
9	Novo Nordisk Investigational Site	Santa Monica	California	United States	90404
10	Novo Nordisk Investigational Site	Spring Valley	California	United States	91978
11	Novo Nordisk Investigational Site	Tustin	California	United States	92780
12	Novo Nordisk Investigational Site	Walnut Creek	California	United States	94598
13	Novo Nordisk Investigational Site	Milford	Connecticut	United States	06460
14	Novo Nordisk Investigational Site	Norwalk	Connecticut	United States	06851
15	Novo Nordisk Investigational Site	Waterbury	Connecticut	United States	06712
16	Novo Nordisk Investigational Site	Washington	District of Columbia	United States	20060
17	Novo Nordisk Investigational Site	Gainesville	Florida	United States	32610
18	Novo Nordisk Investigational Site	Jacksonville	Florida	United States	32205
19	Novo Nordisk Investigational Site	Lake Mary	Florida	United States	32746
20	Novo Nordisk Investigational Site	Orlando	Florida	United States	32804
21	Novo Nordisk Investigational Site	Plantation	Florida	United States	33324
22	Novo Nordisk Investigational Site	West Palm Beach	Florida	United States	33401
23	Novo Nordisk Investigational Site	Atlanta	Georgia	United States	30318
24	Novo Nordisk Investigational Site	Fort Valley	Georgia	United States	31030-5008
25	Novo Nordisk Investigational Site	Honolulu	Hawaii	United States	96814
26	Novo Nordisk Investigational Site	Nampa	Idaho	United States	83686-6011
27	Novo Nordisk Investigational Site	Evansville	Indiana	United States	47714
28	Novo Nordisk Investigational Site	Indianapolis	Indiana	United States	46217
29	Novo Nordisk Investigational Site	New Albany	Indiana	United States	47150
30	Novo Nordisk Investigational Site	Metairie	Louisiana	United States	70002
31	Novo Nordisk Investigational Site	Metairie	Louisiana	United States	70006-2930
32	Novo Nordisk Investigational Site	Hyattsville	Maryland	United States	20782
33	Novo Nordisk Investigational Site	North East	Maryland	United States	21901
34	Novo Nordisk Investigational Site	Rockville	Maryland	United States	20852
35	Novo Nordisk Investigational Site	Eagan	Minnesota	United States	55123
36	Novo Nordisk Investigational Site	Jefferson City	Missouri	United States	65109
37	Novo Nordisk Investigational Site	St. Louis	Missouri	United States	63104
38	Novo Nordisk Investigational Site	Lincoln	Nebraska	United States	68521
39	Novo Nordisk Investigational Site	Omaha	Nebraska	United States	68114
40	Novo Nordisk Investigational Site	Las Vegas	Nevada	United States	89117
41	Novo Nordisk Investigational Site	Lawrenceville	New Jersey	United States	08648
42	Novo Nordisk Investigational Site	Toms River	New Jersey	United States	08755-8050
43	Novo Nordisk Investigational Site	Charlotte	North Carolina	United States	28209
44	Novo Nordisk Investigational Site	Greenville	North Carolina	United States	27834
45	Novo Nordisk Investigational Site	Columbus	Ohio	United States	43203
46	Novo Nordisk Investigational Site	Toledo	Ohio	United States	43606-2920
47	Novo Nordisk Investigational Site	Danville	Pennsylvania	United States	17822
48	Novo Nordisk Investigational Site	Kingston	Pennsylvania	United States	18704
49	Novo Nordisk Investigational Site	Melrose Park	Pennsylvania	United States	19027
50	Novo Nordisk Investigational Site	Philadelphia	Pennsylvania	United States	19107
51	Novo Nordisk Investigational Site	Wilkes Barre	Pennsylvania	United States	18711
52	Novo Nordisk Investigational Site	Charleston	South Carolina	United States	29455
53	Novo Nordisk Investigational Site	Greer	South Carolina	United States	29651
54	Novo Nordisk Investigational Site	Newberry	South Carolina	United States	29108-2249
55	Novo Nordisk Investigational Site	Chattanooga	Tennessee	United States	37404
56	Novo Nordisk Investigational Site	Kingsport	Tennessee	United States	37660
57	Novo Nordisk Investigational Site	Corpus Christi	Texas	United States	78412
58	Novo Nordisk Investigational Site	Dallas	Texas	United States	75230
59	Novo Nordisk Investigational Site	Dallas	Texas	United States	75246
60	Novo Nordisk Investigational Site	Fort Worth	Texas	United States	76113
61	Novo Nordisk Investigational Site	Houston	Texas	United States	77030
62	Novo Nordisk Investigational Site	Round Rock	Texas	United States	78681
63	Novo Nordisk Investigational Site	Salt Lake City	Utah	United States	84107
64	Novo Nordisk Investigational Site	Richmond	Virginia	United States	23233
65	Novo Nordisk Investigational Site	Olympia	Washington	United States	98502
66	Novo Nordisk Investigational Site	Renton	Washington	United States	98057
67	Novo Nordisk Investigational Site	Dimitrovgrad		Bulgaria	6400
68	Novo Nordisk Investigational Site	Ruse		Bulgaria	7000
69	Novo Nordisk Investigational Site	Sofia		Bulgaria	1233
70	Novo Nordisk Investigational Site	Sofia		Bulgaria	1431
71	Novo Nordisk Investigational Site	Sofia		Bulgaria	1606
72	Novo Nordisk Investigational Site	Stara Zagora		Bulgaria	6000
73	Novo Nordisk Investigational Site	Varna		Bulgaria	9010
74	Novo Nordisk Investigational Site	Dresden		Germany	01219
75	Novo Nordisk Investigational Site	Dresden		Germany	01307
76	Novo Nordisk Investigational Site	Frankfurt		Germany	60388
77	Novo Nordisk Investigational Site	Hamburg		Germany	22587
78	Novo Nordisk Investigational Site	Ludwigshafen		Germany	67059
79	Novo Nordisk Investigational Site	Münster		Germany	48145
80	Novo Nordisk Investigational Site	Völklingen		Germany	66333
81	Novo Nordisk Investigational Site	Wangen		Germany	88239
82	Novo Nordisk Investigational Site	Warburg		Germany	34414
83	Novo Nordisk Investigational Site	Shatin, New Territories		Hong Kong
84	Novo Nordisk Investigational Site	Dublin		Ireland	DUBLIN 15
85	Novo Nordisk Investigational Site	Dublin		Ireland	DUBLIN 7
86	Novo Nordisk Investigational Site	Dublin		Ireland	DUBLIN 8
87	Novo Nordisk Investigational Site	Dublin		Ireland
88	Novo Nordisk Investigational Site	Bari		Italy	70124
89	Novo Nordisk Investigational Site	Bergamo		Italy	24127
90	Novo Nordisk Investigational Site	Catania		Italy	95124
91	Novo Nordisk Investigational Site	Chieti Scalo		Italy	66100
92	Novo Nordisk Investigational Site	Firenze		Italy	50141
93	Novo Nordisk Investigational Site	Foggia		Italy	71100
94	Novo Nordisk Investigational Site	Gazi		Italy	98124
95	Novo Nordisk Investigational Site	Messina		Italy	98123
96	Novo Nordisk Investigational Site	Milano		Italy	20132
97	Novo Nordisk Investigational Site	Perugia		Italy	06126
98	Novo Nordisk Investigational Site	Pisa		Italy	56100
99	Novo Nordisk Investigational Site	Roma		Italy	00161
100	Novo Nordisk Investigational Site	Torino		Italy	10126
101	Novo Nordisk Investigational Site	Baia Mare	Maramures	Romania	430123
102	Novo Nordisk Investigational Site	Bucharest		Romania	011234
103	Novo Nordisk Investigational Site	Constanta		Romania	900591
104	Novo Nordisk Investigational Site	Suceava		Romania	720237
105	Novo Nordisk Investigational Site	Timisoara		Romania	300736
106	Novo Nordisk Investigational Site	Arkhangelsk		Russian Federation	163001
107	Novo Nordisk Investigational Site	Barnaul		Russian Federation	656045
108	Novo Nordisk Investigational Site	Krasnoyarsk		Russian Federation	660022
109	Novo Nordisk Investigational Site	Moscow		Russian Federation	119435
110	Novo Nordisk Investigational Site	Moscow		Russian Federation	125367
111	Novo Nordisk Investigational Site	Perm		Russian Federation	614990
112	Novo Nordisk Investigational Site	Saint-Petersburg		Russian Federation	194354
113	Novo Nordisk Investigational Site	Yaroslavl		Russian Federation	150003
114	Novo Nordisk Investigational Site	Bratislava		Slovakia	82102
115	Novo Nordisk Investigational Site	Bratislava		Slovakia	851 01
116	Novo Nordisk Investigational Site	Bratislava		Slovakia	851 05
117	Novo Nordisk Investigational Site	Lucenec		Slovakia	984 01
118	Novo Nordisk Investigational Site	Pretoria	Gauteng	South Africa	0181
119	Novo Nordisk Investigational Site	Durban	KwaZulu-Natal	South Africa	4450
120	Novo Nordisk Investigational Site	Durban	KwaZulu-Natal	South Africa
121	Novo Nordisk Investigational Site	Bloemfontein		South Africa	9301
122	Novo Nordisk Investigational Site	Alcorcón		Spain	28922
123	Novo Nordisk Investigational Site	Almería		Spain	04001
124	Novo Nordisk Investigational Site	Barcelona		Spain	08035
125	Novo Nordisk Investigational Site	Granada		Spain	18012
126	Novo Nordisk Investigational Site	Hospitalet de Llobregat		Spain	08907
127	Novo Nordisk Investigational Site	La Coruña		Spain	15006
128	Novo Nordisk Investigational Site	Madrid		Spain	28040
129	Novo Nordisk Investigational Site	Mostoles - Madrid -		Spain	28935
130	Novo Nordisk Investigational Site	Sabadell		Spain	08208
131	Novo Nordisk Investigational Site	San Juan		Spain	03550
132	Novo Nordisk Investigational Site	Valencia		Spain	46026
133	Novo Nordisk Investigational Site	Antalya		Turkey	07058
134	Novo Nordisk Investigational Site	Istanbul		Turkey	34098
135	Novo Nordisk Investigational Site	Istanbul		Turkey	34390
136	Novo Nordisk Investigational Site	Mersin		Turkey	33070

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

None provided.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT00972283
• Other Study ID Numbers: NN1250-3582; 2008-005777-35; U1111-1111-8648; 2009-015816-17; U1111-1114-9067; NCT01193322
• First Posted: Sep 4, 2009
• Last Update Posted: Apr 6, 2017
• Last Verified: Mar 1, 2017

• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Insulin; Insulin, Globin Zinc; Insulin Glargine; Insulin Aspart

Study Results

Participant Flow

Recruitment Details	The trial was conducted at 123 sites in 12 countries: Bulgaria (8 sites), Germany (8), Hong Kong (1), Ireland (4), Italy (11), Romania (5), Russia (6), Slovakia (4), South Africa (5), Spain (9), Turkey (3) and the United States (U.S.) (59). Some sites did not enroll subjects in the extension period. One site from United States was closed.
Pre-assignment Detail	All subjects who completed the 52-week main trial (NN1250-3582, NCT00972283) and were found to be eligible for the extension trial were offered to participate in the 26-week extension trial (NN1250-3667). The total duration of treatment was up to 78 weeks (52 weeks + 26 weeks).

Arm/Group Title	IDeg OD	IGlar OD
Arm/Group Description	Insulin degludec (IDeg) was given subcutaneously once daily (OD) with main evening meal with insulin aspart (IAsp) as mealtime insulin with or without subject's pre-trial metformin with or without pioglitazone. The regimen was given for a treatment duration of 52 weeks in the main period and for an additional 26 weeks in the extension period.	Insulin glargine (IGlar) was given subcutaneously once daily (OD), according to labelling instructions with insulin aspart (IAsp) as mealtime insulin with or without subject's pre-trial metformin with or without pioglitazone. IGlar was given for a treatment duration of 52 weeks in the main period and for an additional 26 weeks in the extension period.
Period Title: Main: Week 0 to 52 (NN1250-3582)
STARTED	755	251
Full Analysis Set	744	248
Exposed	753	251
COMPLETED	618	211
NOT COMPLETED	137	40
Period Title: Main: Week 0 to 52 (NN1250-3582)
STARTED	566	191
COMPLETED	539	183
NOT COMPLETED	27	8

Baseline Characteristics

Arm/Group Title	IDeg OD	IGlar OD	Total
Arm/Group Description	Insulin degludec (IDeg) was given subcutaneously once daily (OD) with main evening meal with insulin aspart (IAsp) as mealtime insulin with or without subject's pre-trial metformin with or without pioglitazone. The regimen was given for a treatment duration of 52 weeks in the main period and for an additional 26 weeks in the extension period.	Insulin glargine (IGlar) was given subcutaneously once daily (OD), according to labelling instructions with insulin aspart (IAsp) as mealtime insulin with or without subject's pre-trial metformin with or without pioglitazone. IGlar was given for a treatment duration of 52 weeks in the main period and for an additional 26 weeks in the extension period.	Total of all reporting groups
Overall Participants	744	248	992
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.2 (9.1)	58.1 (10.0)	58.9 (9.3)
Sex: Female, Male (Count of Participants)
Female	339 45.6%	115 46.4%	454 45.8%
Male	405 54.4%	133 53.6%	538 54.2%
Glycosylated Haemoglobin (HbA1c) (percentage of glycosylated haemoglobin) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of glycosylated haemoglobin]	8.3 (0.8)	8.4 (0.9)	8.3 (0.8)

Outcome Measures

1. Primary Outcome

Title	Main Trial (Primary Endpoint): Change in Glycosylated Haemoglobin (HbA1c) After 52 Weeks of Treatment
Description	Change from baseline in HbA1c after 52 weeks of treatment
Time Frame	Week 0, Week 52

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) included all randomised subjects and missing data was imputed using last observation carried forward (LOCF)

Arm/Group Title	IDeg OD	IGlar OD
Arm/Group Description	Insulin degludec (IDeg) was given subcutaneously once daily (OD) with main evening meal with insulin aspart (IAsp) as mealtime insulin with or without subject's pre-trial metformin with or without pioglitazone. The regimen was given for a treatment duration of 52 weeks in the main period and for an additional 26 weeks in the extension period.	Insulin glargine (IGlar) was given subcutaneously once daily (OD), according to labelling instructions with insulin aspart (IAsp) as mealtime insulin with or without subject's pre-trial metformin with or without pioglitazone. IGlar was given for a treatment duration of 52 weeks in the main period and for an additional 26 weeks in the extension period.
Measure Participants	744	248
Mean (Standard Deviation) [percentage of glycosylated haemoglobin]	-1.17 (1.03)	-1.29 (0.98)

2. Secondary Outcome

Title	Extension Trial (Secondary Endpoint): Change in Glycosylated Haemoglobin (HbA1c) After 78 Weeks of Treatment
Description	Change from baseline in HbA1c after 78 weeks of treatment
Time Frame	Week 0, Week 78

Outcome Measure Data

Analysis Population Description

The FAS included all randomised subjects in the main trial including subjects carried through to the extension trial and missing data was imputed using LOCF

Arm/Group Title	IDeg OD	IGlar OD
Arm/Group Description	Insulin degludec (IDeg) was given subcutaneously once daily (OD) with main evening meal with insulin aspart (IAsp) as mealtime insulin with or without subject's pre-trial metformin with or without pioglitazone. The regimen was given for a treatment duration of 52 weeks in the main period and for an additional 26 weeks in the extension period.	Insulin glargine (IGlar) was given subcutaneously once daily (OD), according to labelling instructions with insulin aspart (IAsp) as mealtime insulin with or without subject's pre-trial metformin with or without pioglitazone. IGlar was given for a treatment duration of 52 weeks in the main period and for an additional 26 weeks in the extension period.
Measure Participants	744	248
Mean (Standard Deviation) [percentage of glycosylated haemoglobin]	-0.95 (1.13)	-1.15 (0.99)

3. Secondary Outcome

Title	Main Trial (Secondary Endpoint): Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) at Week 52
Description	Mean of 9-point SMPG at 52 weeks of treatment. Plasma glucose measured: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner, bedtime, at 4 am and before breakfast.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

The FAS included all randomised subjects and missing data was imputed using LOCF. For 36 subjects all 9-point SMPG values were missing.

Arm/Group Title	IDeg OD	IGlar OD
Arm/Group Description	Insulin degludec (IDeg) was given subcutaneously once daily (OD) with main evening meal with insulin aspart (IAsp) as mealtime insulin with or without subject's pre-trial metformin with or without pioglitazone. The regimen was given for a treatment duration of 52 weeks in the main period and for an additional 26 weeks in the extension period.	Insulin glargine (IGlar) was given subcutaneously once daily (OD), according to labelling instructions with insulin aspart (IAsp) as mealtime insulin with or without subject's pre-trial metformin with or without pioglitazone. IGlar was given for a treatment duration of 52 weeks in the main period and for an additional 26 weeks in the extension period.
Measure Participants	715	241
Mean (Standard Deviation) [mmol/L]	7.3 (1.8)	6.9 (1.5)

4. Secondary Outcome

Title	Extension Trial (Secondary Endpoint): Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) at Week 78
Description	Mean of the SMPG at 78 weeks of treatment. Plasma glucose measured: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner, bedtime, at 4 am, before breakfast.
Time Frame	Week 78

Outcome Measure Data

Analysis Population Description

The FAS included all randomised subjects in the main trial including subjects carried through to the extension trial and missing data was imputed using LOCF. For 36 subjects all 9-point SMPG values were missing.

Arm/Group Title	IDeg OD	IGlar OD
Arm/Group Description	Insulin degludec (IDeg) was given subcutaneously once daily (OD) with main evening meal with insulin aspart (IAsp) as mealtime insulin with or without subject's pre-trial metformin with or without pioglitazone. The regimen was given for a treatment duration of 52 weeks in the main period and for an additional 26 weeks in the extension period.	Insulin glargine (IGlar) was given subcutaneously once daily (OD), according to labelling instructions with insulin aspart (IAsp) as mealtime insulin with or without subject's pre-trial metformin with or without pioglitazone. IGlar was given for a treatment duration of 52 weeks in the main period and for an additional 26 weeks in the extension period.
Measure Participants	716	240
Mean (Standard Deviation) [mmol/L]	7.2 (1.9)	6.8 (1.4)

5. Primary Outcome

Title	Extension Trial (Primary Endpoint): Rate of Confirmed Hypoglycaemic Episodes
Description	Rate of confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes are defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes are defined as able to treat her/himself and plasma glucose below 3.1 mmol/L.
Time Frame	Week 0 to Week 78 + 7 days follow up

Outcome Measure Data

Analysis Population Description

Safety analysis set (SAS) included all subjects who received at least one dose of the investigational product or its comparator in the main trial including subjects carried through to the extension trial.

Arm/Group Title	IDeg OD	IGlar OD
Arm/Group Description	Insulin degludec (IDeg) was given subcutaneously once daily (OD) with main evening meal with insulin aspart (IAsp) as mealtime insulin with or without subject's pre-trial metformin with or without pioglitazone. The regimen was given for a treatment duration of 52 weeks in the main period and for an additional 26 weeks in the extension period.	Insulin glargine (IGlar) was given subcutaneously once daily (OD), according to labelling instructions with insulin aspart (IAsp) as mealtime insulin with or without subject's pre-trial metformin with or without pioglitazone. IGlar was given for a treatment duration of 52 weeks in the main period and for an additional 26 weeks in the extension period.
Measure Participants	753	251
Number [Episodes/100 years of patient exposure]	1039	1271

6. Primary Outcome

Title	Extension Trial (Primary Endpoint): Rate of Nocturnal Confirmed Hypoglycaemic Episodes
Description	Rate of confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes are defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes are defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. Nocturnal hypoglycaemic episodes are defined as occurring between 00:01 and 05:59 a.m.
Time Frame	Week 0 to Week 78 + 7 days follow up

Outcome Measure Data

Analysis Population Description

The SAS included all subjects who received at least one dose of the investigational product or its comparator in the main trial including subjects carried through to the extension trial.

Arm/Group Title	IDeg OD	IGlar OD
Arm/Group Description	Insulin degludec (IDeg) was given subcutaneously once daily (OD) with main evening meal with insulin aspart (IAsp) as mealtime insulin with or without subject's pre-trial metformin with or without pioglitazone. The regimen was given for a treatment duration of 52 weeks in the main period and for an additional 26 weeks in the extension period.	Insulin glargine (IGlar) was given subcutaneously once daily (OD), according to labelling instructions with insulin aspart (IAsp) as mealtime insulin with or without subject's pre-trial metformin with or without pioglitazone. IGlar was given for a treatment duration of 52 weeks in the main period and for an additional 26 weeks in the extension period.
Measure Participants	753	251
Number [Episodes/100 years of patient exposure]	134	176

7. Primary Outcome

Title	Rate of Treatment Emergent Adverse Events (AEs)
Description	Corresponds to rate of AEs per 100 patient years of exposure. Mild AEs: no or transient symptoms, no interference with subject's daily activities. Moderate AEs: marked symptoms, moderate interference with subject's daily activities. Severe AEs: considerable interference with subject's daily activities, unacceptable. Serious adverse event (SAE): AE that at any dose results in any of the following: death, a life-threatening experience, in-subject hospitalization/prolongation of existing hospitalisation, persistent/significant disability/incapacity/congenital anomaly/birth defect.
Time Frame	Week 0 to Week 78 + 7 days follow up

Outcome Measure Data

Analysis Population Description

The SAS included all subjects who received at least one dose of the investigational product or its comparator.

Arm/Group Title	IDeg OD	IGlar OD
Arm/Group Description	Insulin degludec (IDeg) was given subcutaneously once daily (OD) with main evening meal with insulin aspart (IAsp) as mealtime insulin with or without subject's pre-trial metformin with or without pioglitazone. The regimen was given for a treatment duration of 52 weeks in the main period and for an additional 26 weeks in the extension period.	Insulin glargine (IGlar) was given subcutaneously once daily (OD), according to labelling instructions with insulin aspart (IAsp) as mealtime insulin with or without subject's pre-trial metformin with or without pioglitazone. IGlar was given for a treatment duration of 52 weeks in the main period and for an additional 26 weeks in the extension period.
Measure Participants	753	251
Adverse events (AEs)	411	403
Serious AE	20	20
Severe AE	24	20
Moderate AE	113	118
Mild AE	274	266
Fatal AE	1	1

8. Secondary Outcome

Title	Main Trial (Secondary Endpoint): Rate of Confirmed Hypoglycaemic Episodes
Description	Rate of confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes are defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes are defined as able to treat her/himself and plasma glucose below 3.1 mmol/L.
Time Frame	Week 0 to Week 52 + 7 days follow up

Outcome Measure Data

Analysis Population Description

The SAS included all subjects who received at least one dose of the investigational product or its comparator.

Arm/Group Title	IDeg OD	IGlar OD
Arm/Group Description	Insulin degludec (IDeg) was given subcutaneously once daily (OD) with main evening meal with insulin aspart (IAsp) as mealtime insulin with or without subject's pre-trial metformin with or without pioglitazone. The regimen was given for a treatment duration of 52 weeks in the main period and for an additional 26 weeks in the extension period.	Insulin glargine (IGlar) was given subcutaneously once daily (OD), according to labelling instructions with insulin aspart (IAsp) as mealtime insulin with or without subject's pre-trial metformin with or without pioglitazone. IGlar was given for a treatment duration of 52 weeks in the main period and for an additional 26 weeks in the extension period.
Measure Participants	753	251
Number [Episodes/100 years of patient exposure]	1109	1363

9. Secondary Outcome

Title	Main Trial (Secondary Endpoint): Rate of Nocturnal Confirmed Hypoglycaemic Episodes
Description	Rate of confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes are defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes are defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. Nocturnal hypoglycaemic episodes are defined as occurring between 00:01 and 05:59 a.m.
Time Frame	Week 0 to Week 52 + 7 days follow up

Outcome Measure Data

Analysis Population Description

The SAS included all subjects who received at least one dose of the investigational product or its comparator.

Arm/Group Title	IDeg OD	IGlar OD
Arm/Group Description	Insulin degludec (IDeg) was given subcutaneously once daily (OD) with main evening meal with insulin aspart (IAsp) as mealtime insulin with or without subject's pre-trial metformin with or without pioglitazone. The regimen was given for a treatment duration of 52 weeks in the main period and for an additional 26 weeks in the extension period.	Insulin glargine (IGlar) was given subcutaneously once daily (OD), according to labelling instructions with insulin aspart (IAsp) as mealtime insulin with or without subject's pre-trial metformin with or without pioglitazone. IGlar was given for a treatment duration of 52 weeks in the main period and for an additional 26 weeks in the extension period.
Measure Participants	753	251
Number [Episodes/100 years of patient exposure]	139	184

Adverse Events

Time Frame	Adverse events were collected in a time frame of 78 weeks + 7 days follow up.
Adverse Event Reporting Description	The SAS included all subjects who received at least one dose of investigational product or its comparator.
Arm/Group Title	IDeg OD		IGlar OD
Arm/Group Description	Insulin degludec (IDeg) was given subcutaneously once daily (OD) with main evening meal with insulin aspart (IAsp) as mealtime insulin with or without subject's pre-trial metformin with or without pioglitazone. The regimen was given for a treatment duration of 52 weeks in the main period and for an additional 26 weeks in the extension period.		Insulin glargine (IGlar) was given subcutaneously once daily (OD), according to labelling instructions with insulin aspart (IAsp) as mealtime insulin with or without subject's pre-trial metformin with or without pioglitazone. IGlar was given for a treatment duration of 52 weeks in the main period and for an additional 26 weeks in the extension period.
All Cause Mortality
	IDeg OD		IGlar OD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	IDeg OD		IGlar OD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	139/753 (18.5%)		53/251 (21.1%)
Blood and lymphatic system disorders
Anaemia	1/753 (0.1%)	1	0/251 (0%)	0
Autoimmune thrombocytopenia	1/753 (0.1%)	1	0/251 (0%)	0
Cardiac disorders
Acute coronary syndrome	0/753 (0%)	0	1/251 (0.4%)	2
Acute myocardial infarction	5/753 (0.7%)	5	0/251 (0%)	0
Angina pectoris	3/753 (0.4%)	3	0/251 (0%)	0
Angina unstable	3/753 (0.4%)	3	0/251 (0%)	0
Aortic valve incompetence	1/753 (0.1%)	1	0/251 (0%)	0
Atrial fibrillation	2/753 (0.3%)	2	1/251 (0.4%)	1
Bradycardia	1/753 (0.1%)	1	0/251 (0%)	0
Cardiac arrest	1/753 (0.1%)	1	0/251 (0%)	0
Cardiac failure	2/753 (0.3%)	2	0/251 (0%)	0
Cardiac failure congestive	2/753 (0.3%)	2	3/251 (1.2%)	3
Cardio-respiratory arrest	1/753 (0.1%)	1	0/251 (0%)	0
Coronary artery disease	8/753 (1.1%)	9	3/251 (1.2%)	3
Coronary artery occlusion	1/753 (0.1%)	1	0/251 (0%)	0
Coronary artery stenosis	0/753 (0%)	0	2/251 (0.8%)	2
Coronary artery thrombosis	1/753 (0.1%)	1	0/251 (0%)	0
Hypertensive heart disease	1/753 (0.1%)	1	0/251 (0%)	0
Myocardial infarction	2/753 (0.3%)	2	2/251 (0.8%)	2
Myocardial ischaemia	3/753 (0.4%)	3	0/251 (0%)	0
Sinus bradycardia	0/753 (0%)	0	1/251 (0.4%)	1
Ventricular hypokinesia	1/753 (0.1%)	1	0/251 (0%)	0
Cardiovascular disorder	0/753 (0%)	0	1/251 (0.4%)	1
Pericarditis	1/753 (0.1%)	1	0/251 (0%)	0
Congenital, familial and genetic disorders
Corneal dystrophy	1/753 (0.1%)	1	0/251 (0%)	0
Ear and labyrinth disorders
Tympanic membrane disorder	0/753 (0%)	0	1/251 (0.4%)	1
Mastoiditis	1/753 (0.1%)	1	0/251 (0%)	0
Eye disorders
Cataract	1/753 (0.1%)	1	0/251 (0%)	0
Diabetic retinopathy	1/753 (0.1%)	1	0/251 (0%)	0
Gastrointestinal disorders
Colitis	1/753 (0.1%)	1	0/251 (0%)	0
Duodenal ulcer	1/753 (0.1%)	1	0/251 (0%)	0
Dyspepsia	1/753 (0.1%)	1	0/251 (0%)	0
Erosive oesophagitis	1/753 (0.1%)	1	0/251 (0%)	0
Gastroduodenitis	0/753 (0%)	0	1/251 (0.4%)	1
Haematemesis	1/753 (0.1%)	1	0/251 (0%)	0
Ileus paralytic	1/753 (0.1%)	1	0/251 (0%)	0
Oesophageal rupture	1/753 (0.1%)	1	0/251 (0%)	0
Pancreatitis	1/753 (0.1%)	1	0/251 (0%)	0
Rectal haemorrhage	1/753 (0.1%)	1	0/251 (0%)	0
Umbilical hernia	1/753 (0.1%)	1	0/251 (0%)	0
Duodenitis	1/753 (0.1%)	1	0/251 (0%)	0
Hiatus hernia	1/753 (0.1%)	1	0/251 (0%)	0
Oesophageal varices haemorrhage	1/753 (0.1%)	1	0/251 (0%)	0
Pancreatitis acute	1/753 (0.1%)	1	0/251 (0%)	0
Cholecystitis	1/753 (0.1%)	1	0/251 (0%)	0
Cholecystitis acute	2/753 (0.3%)	2	0/251 (0%)	0
General disorders
Chest discomfort	2/753 (0.3%)	2	0/251 (0%)	0
Chest pain	1/753 (0.1%)	1	1/251 (0.4%)	1
Gait disturbance	0/753 (0%)	0	1/251 (0.4%)	1
Medical device complication	1/753 (0.1%)	1	0/251 (0%)	0
Non-cardiac chest pain	4/753 (0.5%)	4	0/251 (0%)	0
Adhesion	0/753 (0%)	0	1/251 (0.4%)	1
Death	1/753 (0.1%)	1	0/251 (0%)	0
Pyrexia	1/753 (0.1%)	1	0/251 (0%)	0
Hepatobiliary disorders
Biliary colic	1/753 (0.1%)	1	0/251 (0%)	0
Cholelithiasis	2/753 (0.3%)	2	0/251 (0%)	0
Gallbladder pain	1/753 (0.1%)	1	0/251 (0%)	0
Hepatitis acute	1/753 (0.1%)	1	0/251 (0%)	0
Cholecystitis infective	0/753 (0%)	0	1/251 (0.4%)	1
Immune system disorders
Food allergy	1/753 (0.1%)	1	0/251 (0%)	0
Infections and infestations
Abscess jaw	1/753 (0.1%)	1	0/251 (0%)	0
Bronchitis	2/753 (0.3%)	2	0/251 (0%)	0
Bronchopulmonary aspergillosis	1/753 (0.1%)	1	0/251 (0%)	0
Cellulitis	2/753 (0.3%)	2	1/251 (0.4%)	1
Diabetic foot infection	1/753 (0.1%)	1	0/251 (0%)	0
Endocarditis	1/753 (0.1%)	1	0/251 (0%)	0
Gastroenteritis	1/753 (0.1%)	1	1/251 (0.4%)	1
Gastroenteritis viral	2/753 (0.3%)	2	0/251 (0%)	0
Incision site abscess	1/753 (0.1%)	1	0/251 (0%)	0
Infected sebaceous cyst	1/753 (0.1%)	1	0/251 (0%)	0
Pneumonia	2/753 (0.3%)	2	1/251 (0.4%)	1
Pneumonia bacterial	1/753 (0.1%)	1	0/251 (0%)	0
Pneumonia staphylococcal	1/753 (0.1%)	1	0/251 (0%)	0
Pyelonephritis acute	1/753 (0.1%)	1	1/251 (0.4%)	1
Pyelonephritis chronic	1/753 (0.1%)	1	0/251 (0%)	0
Respiratory tract infection	1/753 (0.1%)	1	0/251 (0%)	0
Salmonella sepsis	1/753 (0.1%)	1	0/251 (0%)	0
Streptococcal bacteraemia	1/753 (0.1%)	1	0/251 (0%)	0
Tracheobronchitis	1/753 (0.1%)	1	0/251 (0%)	0
Urinary tract infection	0/753 (0%)	0	1/251 (0.4%)	1
Wound infection	1/753 (0.1%)	1	0/251 (0%)	0
Herpes zoster	1/753 (0.1%)	1	0/251 (0%)	0
Implant site infection	1/753 (0.1%)	1	0/251 (0%)	0
Injury, poisoning and procedural complications
Accidental overdose	1/753 (0.1%)	1	0/251 (0%)	0
Ankle fracture	1/753 (0.1%)	1	1/251 (0.4%)	1
Contrast media reaction	1/753 (0.1%)	1	0/251 (0%)	0
Hip fracture	1/753 (0.1%)	1	0/251 (0%)	0
Humerus fracture	1/753 (0.1%)	1	1/251 (0.4%)	1
Joint injury	1/753 (0.1%)	1	0/251 (0%)	0
Road traffic accident	1/753 (0.1%)	1	0/251 (0%)	0
Traumatic brain injury	1/753 (0.1%)	1	0/251 (0%)	0
Wrong drug administered	2/753 (0.3%)	2	0/251 (0%)	0
Fall	1/753 (0.1%)	1	1/251 (0.4%)	1
Fibular fracture	0/753 (0%)	0	1/251 (0.4%)	1
Radius fracture	0/753 (0%)	0	1/251 (0.4%)	1
Investigations
Blood creatinine increased	1/753 (0.1%)	1	0/251 (0%)	0
Cardiac murmur	1/753 (0.1%)	1	0/251 (0%)	0
Oxygen saturation decreased	1/753 (0.1%)	1	0/251 (0%)	0
Metabolism and nutrition disorders
Diabetes mellitus inadequate control	1/753 (0.1%)	1	0/251 (0%)	0
Hypoglycaemia	13/753 (1.7%)	13	2/251 (0.8%)	2
Hypoglycaemia unawareness	1/753 (0.1%)	1	0/251 (0%)	0
Hypoglycaemic seizure	1/753 (0.1%)	1	0/251 (0%)	0
Hypoglycaemic unconsciousness	6/753 (0.8%)	10	1/251 (0.4%)	1
Dehydration	0/753 (0%)	0	1/251 (0.4%)	1
Musculoskeletal and connective tissue disorders
Musculoskeletal pain	1/753 (0.1%)	1	0/251 (0%)	0
Osteoarthritis	2/753 (0.3%)	2	0/251 (0%)	0
Spinal osteoarthritis	0/753 (0%)	0	1/251 (0.4%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bone neoplasm malignant	1/753 (0.1%)	1	0/251 (0%)	0
Breast cancer	1/753 (0.1%)	1	1/251 (0.4%)	1
Colon cancer	1/753 (0.1%)	1	0/251 (0%)	0
Colon cancer stage III	0/753 (0%)	0	1/251 (0.4%)	1
Metastatic neoplasm	0/753 (0%)	0	1/251 (0.4%)	1
Penis carcinoma	1/753 (0.1%)	1	0/251 (0%)	0
Polycythaemia vera	1/753 (0.1%)	1	0/251 (0%)	0
Uterine cancer	1/753 (0.1%)	1	0/251 (0%)	0
B cell lymphoma stage-1	1/753 (0.1%)	1	0/251 (0%)	0
Bile duct cancer	1/753 (0.1%)	1	0/251 (0%)	0
Bronchial carcinoma	1/753 (0.1%)	1	0/251 (0%)	0
Metastasis to central nervous system	1/753 (0.1%)	1	0/251 (0%)	0
Tongue carcinoma stage-1	1/753 (0.1%)	1	0/251 (0%)	0
Nervous system disorders
Carotid artery stenosis	1/753 (0.1%)	1	0/251 (0%)	0
Cerebrovascular accident	3/753 (0.4%)	3	0/251 (0%)	0
Cerebrovascular insufficiency	0/753 (0%)	0	1/251 (0.4%)	1
Dizziness	0/753 (0%)	0	1/251 (0.4%)	1
Facial nerve disorder	0/753 (0%)	0	1/251 (0.4%)	1
Haemorrhage intracranial	1/753 (0.1%)	1	0/251 (0%)	0
Hemiparesis	1/753 (0.1%)	1	0/251 (0%)	0
Hypoaesthesia	0/753 (0%)	0	1/251 (0.4%)	1
Ischaemic stroke	1/753 (0.1%)	1	0/251 (0%)	0
Transient ischaemic attack	3/753 (0.4%)	3	1/251 (0.4%)	1
VIth nerve paralysis	1/753 (0.1%)	1	0/251 (0%)	0
Vertebrobasilar insufficiency	1/753 (0.1%)	1	0/251 (0%)	0
Brain stem haemorrhage	1/753 (0.1%)	1	0/251 (0%)	0
Cauda equina syndrome	0/753 (0%)	0	1/251 (0.4%)	1
Psychiatric disorders
Confusional state	1/753 (0.1%)	1	0/251 (0%)	0
Depression suicidal	0/753 (0%)	0	1/251 (0.4%)	1
Eating disorder	0/753 (0%)	0	1/251 (0.4%)	1
Renal and urinary disorders
Acute prerenal failure	1/753 (0.1%)	1	0/251 (0%)	0
Calculus ureteric	0/753 (0%)	0	1/251 (0.4%)	1
Nephrolithiasis	0/753 (0%)	0	1/251 (0.4%)	1
Urethral stenosis	1/753 (0.1%)	1	0/251 (0%)	0
Pyelonephritis	1/753 (0.1%)	1	0/251 (0%)	0
Inter capillary glomerulosclerosis	0/753 (0%)	0	1/251 (0.4%)	1
Reproductive system and breast disorders
Metrorrhagia	0/753 (0%)	0	1/251 (0.4%)	1
Uterine polyp	0/753 (0%)	0	1/251 (0.4%)	1
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema	1/753 (0.1%)	1	0/251 (0%)	0
Acute respiratory failure	0/753 (0%)	0	1/251 (0.4%)	1
Asthma	3/753 (0.4%)	3	1/251 (0.4%)	1
Bronchitis chronic	1/753 (0.1%)	1	0/251 (0%)	0
Chronic obstructive pulmonary disease	2/753 (0.3%)	2	3/251 (1.2%)	4
Dyspnoea exertional	0/753 (0%)	0	1/251 (0.4%)	1
Emphysema	1/753 (0.1%)	1	0/251 (0%)	0
Pneumothorax spontaneous tension	1/753 (0.1%)	1	0/251 (0%)	0
Respiratory failure	1/753 (0.1%)	1	0/251 (0%)	0
Skin and subcutaneous tissue disorders
Pruritus generalised	0/753 (0%)	0	1/251 (0.4%)	1
Urticaria	1/753 (0.1%)	1	0/251 (0%)	0
Dermatitis allergic	1/753 (0.1%)	1	0/251 (0%)	0
Surgical and medical procedures
Gastric bypass	1/753 (0.1%)	1	0/251 (0%)	0
Vascular disorders
Arteriosclerosis	1/753 (0.1%)	1	0/251 (0%)	0
Hypertension	3/753 (0.4%)	3	1/251 (0.4%)	1
Peripheral vascular disorder	1/753 (0.1%)	1	0/251 (0%)	0
Diastolic hypertension	0/753 (0%)	0	1/251 (0.4%)	1
Hypotension	0/753 (0%)	0	1/251 (0.4%)	1
Other (Not Including Serious) Adverse Events
	IDeg OD		IGlar OD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	447/753 (59.4%)		146/251 (58.2%)
Gastrointestinal disorders
Diarrhoea	59/753 (7.8%)	73	26/251 (10.4%)	31
Vomiting	28/753 (3.7%)	39	14/251 (5.6%)	20
Nausea	39/753 (5.2%)	45	15/251 (6%)	18
General disorders
Oedema peripheral	55/753 (7.3%)	69	17/251 (6.8%)	20
Infections and infestations
Influenza	58/753 (7.7%)	68	20/251 (8%)	23
Nasopharyngitis	124/753 (16.5%)	212	37/251 (14.7%)	61
Upper respiratory tract infection	123/753 (16.3%)	212	42/251 (16.7%)	70
Sinusitis	45/753 (6%)	64	18/251 (7.2%)	21
Injury, poisoning and procedural complications
Wrong drug administered	58/753 (7.7%)	66	9/251 (3.6%)	9
Musculoskeletal and connective tissue disorders
Arthralgia	43/753 (5.7%)	55	26/251 (10.4%)	36
Back pain	56/753 (7.4%)	66	21/251 (8.4%)	25
Pain in extremity	47/753 (6.2%)	55	19/251 (7.6%)	19
Nervous system disorders
Headache	71/753 (9.4%)	153	20/251 (8%)	32
Respiratory, thoracic and mediastinal disorders
Cough	61/753 (8.1%)	71	21/251 (8.4%)	29
Bronchitis	49/753 (6.5%)	64	13/251 (5.2%)	19
Vascular disorders
Hypertension	50/753 (6.6%)	59	14/251 (5.6%)	15

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Novo Nordisk maintains the right to be informed of any Investigator plans for publication and to review any scientific paper, presentation, communication or other information concerning the investigation described in this protocol. Any such communication must be submitted in writing to the Novo Nordisk trial manager prior to submission for comments. Comments will be given within four weeks from receipt of the planned communication.