SWITCH 1: A Trial Comparing the Safety and Efficacy of Insulin Degludec and Insulin Glargine, Both With Insulin Aspart as Mealtime Insulin in Subjects With Type 1 Diabetes

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02034513
• Collaborator: (none)
• Enrollment: 501
• Locations: 99
• Arms: 2
• Actual Duration (Months): 24.2
• Patients Per Site: 5.1
• Patients Per Site Per Month: 0.2

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 compare the safety and efficacy of insulin degludec (IDeg) and insulin glargine (IGlar), both with insulin aspart (IAsp) as mealtime insulin in subjects with type 1 diabetes.

Condition or Disease	Intervention/Treatment	Phase
Diabetes; Diabetes Mellitus, Type 1	Drug: insulin degludec; Drug: insulin glargine; Drug: insulin aspart	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 501 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomised, Double Blind, Cross-over Trial Comparing the Safety and Efficacy of Insulin Degludec and Insulin Glargine, Both With Insulin Aspart as Mealtime Insulin in Subjects With Type 1 Diabetes (SWITCH 1)
• Actual Study Start Date: Jan 5, 2014
• Actual Primary Completion Date: Jan 11, 2016
• Actual Study Completion Date: Jan 11, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IDeg OD + IAsp followed by IGlar OD + IAsp Each treatment period consists of a 16-week wash-out period and a 16-week maintenance period	Drug: insulin degludec; Administered once daily, injected s.c. / subcutaneously (under the skin). Dose is individually adjusted.; Drug: insulin glargine; Administered once daily, injected s.c. / subcutaneously (under the skin). Dose is individually adjusted.; Drug: insulin aspart; Administered 2-4 times daily injected s.c. / subcutaneously (under the skin). Dose is individually adjusted.
Active Comparator: IGlar OD + IAsp followed by IDeg OD + IAsp Each treatment period consists of a 16-week wash-out period and a 16-week maintenance period	Drug: insulin degludec; Administered once daily, injected s.c. / subcutaneously (under the skin). Dose is individually adjusted.; Drug: insulin glargine; Administered once daily, injected s.c. / subcutaneously (under the skin). Dose is individually adjusted.; Drug: insulin aspart; Administered 2-4 times daily injected s.c. / subcutaneously (under the skin). Dose is individually adjusted.

Outcome Measures

Primary Outcome Measures

1. Number of Treatment Emergent Severe or BG (Blood Glucose) Confirmed Symptomatic Hypoglycaemic Episodes During the Maintenance Period [A 16-week treatment period.]

   Severe or blood glucose (BG) confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe and/or BG confirmed by a plasma glucose value of <3.1 mmol/L (56 mg/dL), with symptoms consistent with hypoglycaemia. Treatment emergent hypoglycaemic episode was defined as an event with onset date on or after the first day of exposure to randomised treatment and no later than the last day of randomised treatment. Maintenance period: 16 weeks of treatment, in each treatment period (Week 16-32 and Week 48-64).

Secondary Outcome Measures

1. Number of Treatment Emergent Severe or BG Confirmed Symptomatic Nocturnal Hypoglycaemic Episodes During the Maintenance Period [After 16 weeks of treatment, in each treatment period (Week 16-32 and Week 48-64)]

   Severe or BG confirmed symptomatic nocturnal hypoglycaemic episodes were defined as episodes that were severe and/or BG confirmed by a plasma glucose value of <3.1 mmol/L (56 mg/dL), with symptoms consistent with hypoglycaemia and with time of onset between 00:01 and 05.59 a.m., both inclusive. Treatment emergent hypoglycaemic episode was defined as an event with onset date on or after the first day of exposure to randomised treatment and no later than the last day of randomised treatment.

2. Proportion of Subjects With One or More Severe Hypoglycaemic Episodes During the Maintenance Period [After 16 weeks of treatment, in each treatment period (Week 16-32 and Week 48-64)]

   Percentage of subjects who experienced one or more severe hypoglycaemic episodes during the maintenance period. Severe hypoglycaemia (according to the American Diabetes Association 2013 definition): A hypoglycaemic episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. Plasma glucose values may not be available during an event, but neurological recovery following the return of plasma glucose to normal is considered sufficient evidence that the event was induced by a low plasma glucose concentration.

3. Incidence of Treatment Emergent Adverse Events [During 32 weeks of treatment for each treatment period]

   Treatment emergent adverse event was defined as an event with onset date on or after the first day of exposure to randomised treatment and no later than the last day of randomised treatment.

4. Change From Baseline in HbA1c (Glycosylated Haemoglobin) [Week 32, Week 64]

   Change from baseline in HbA1c (glycosylated haemoglobin) at week 32 (treatment period 1) and at week 64 (treatment period 2). Week 32 HbA1c absolute value was considered as baseline for calculating change from baseline in HbA1c at week 64.

5. FPG (Fasting Plasma Glucose) [Week 32 and Week 64]

   Fasting plasma glucose values at week 32 and week 64.

Eligibility Criteria

Criteria

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

Inclusion Criteria: - Subjects fulfilling at least one of the below criteria: a) Experienced at least one severe hypo episode within the last year (according to the ADA (American Diabetes Association) definition, April 2013) b) Moderate chronic renal failure, defined as glomerular filtration rate 30 - 59 mL/min/1.73 m^2 per CKD-Epi (chronic kidney disease epidemiology collaboration) c) Hypoglycaemic symptom unawareness d) Diabetes mellitus duration for more than 15 years e) Recent episode of hypoglycaemia (defined by symptoms of hypoglycaemia and/or episode with low glucose measurement (below or equal to 70 mg/dL [below or equal to 3.9 mmol/L])) within the last 12 weeks prior to Visit 1 (screening) - Male or female, age at least 18 years at the time of signing informed consent

• Type 1 diabetes mellitus (diagnosed clinically) for at least 52 weeks prior to Visit 1 - Current treatment with a basal-bolus regimen consisting of neutral protamine Hagedorn (NPH) insulin OD (once daily) / BID (twice daily) or insulin detemir (IDet) OD / BID plus 2-4 daily injections of any rapid acting meal time insulin or CSII (with rapid acting insulin) for at least 26 weeks prior to Visit 1 - HbA1c (glycosylated haemoglobin) below or equal to 10% by central laboratory analysis - BMI (body mass index) below or equal to 45 kg/m^2 Exclusion Criteria: - Treatment with IGlar or IDeg within the last 26 weeks prior to Visit 1 (short term use [less than or equal to 2 weeks] is allowed, but not within 4 weeks prior to screening) - Use of any other anti-diabetic agent than those stated in the inclusion criteria within the last 26 weeks prior to Visit 1

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Birmingham	Alabama	United States	35215-7502
2	Novo Nordisk Investigational Site	Goodyear	Arizona	United States	85395
3	Novo Nordisk Investigational Site	Concord	California	United States	94520
4	Novo Nordisk Investigational Site	Escondido	California	United States	92025
5	Novo Nordisk Investigational Site	Fresno	California	United States	93720
6	Novo Nordisk Investigational Site	La Jolla	California	United States	92037
7	Novo Nordisk Investigational Site	Long Beach	California	United States	90807
8	Novo Nordisk Investigational Site	Rancho Cucamonga	California	United States	91730-3063
9	Novo Nordisk Investigational Site	San Mateo	California	United States	94401
10	Novo Nordisk Investigational Site	San Ramon	California	United States	94583
11	Novo Nordisk Investigational Site	Santa Monica	California	United States	90404
12	Novo Nordisk Investigational Site	Upland	California	United States	91786
13	Novo Nordisk Investigational Site	Ventura	California	United States	93003
14	Novo Nordisk Investigational Site	Denver	Colorado	United States	80220
15	Novo Nordisk Investigational Site	Cooper City	Florida	United States	33024
16	Novo Nordisk Investigational Site	Fleming Island	Florida	United States	32003
17	Novo Nordisk Investigational Site	Fort Lauderdale	Florida	United States	33312
18	Novo Nordisk Investigational Site	Hialeah	Florida	United States	33012
19	Novo Nordisk Investigational Site	Jacksonville	Florida	United States	32204
20	Novo Nordisk Investigational Site	Jacksonville	Florida	United States	32207
21	Novo Nordisk Investigational Site	Jacksonville	Florida	United States	32216
22	Novo Nordisk Investigational Site	Jacksonville	Florida	United States	32256
23	Novo Nordisk Investigational Site	Miami Springs	Florida	United States	33166
24	Novo Nordisk Investigational Site	Miami	Florida	United States	33130
25	Novo Nordisk Investigational Site	Miami	Florida	United States	33156
26	Novo Nordisk Investigational Site	Miami	Florida	United States	33175
27	Novo Nordisk Investigational Site	New Port Richey	Florida	United States	34652
28	Novo Nordisk Investigational Site	Pembroke Pines	Florida	United States	33026
29	Novo Nordisk Investigational Site	Port Charlotte	Florida	United States	33952
30	Novo Nordisk Investigational Site	Port Orange	Florida	United States	32127
31	Novo Nordisk Investigational Site	Lawrenceville	Georgia	United States	30046
32	Novo Nordisk Investigational Site	Idaho Falls	Idaho	United States	83404-7596
33	Novo Nordisk Investigational Site	Arlington Heights	Illinois	United States	60005-4144
34	Novo Nordisk Investigational Site	Chicago	Illinois	United States	60611
35	Novo Nordisk Investigational Site	Crystal Lake	Illinois	United States	60012
36	Novo Nordisk Investigational Site	Skokie	Illinois	United States	60077
37	Novo Nordisk Investigational Site	Anderson	Indiana	United States	46011
38	Novo Nordisk Investigational Site	Indianapolis	Indiana	United States	46234
39	Novo Nordisk Investigational Site	Council Bluffs	Iowa	United States	51501
40	Novo Nordisk Investigational Site	West Des Moines	Iowa	United States	50265
41	Novo Nordisk Investigational Site	Lenexa	Kansas	United States	66219
42	Novo Nordisk Investigational Site	Topeka	Kansas	United States	66606
43	Novo Nordisk Investigational Site	Lexington	Kentucky	United States	40503
44	Novo Nordisk Investigational Site	Livonia	Michigan	United States	48152
45	Novo Nordisk Investigational Site	Hazelwood	Missouri	United States	63042
46	Novo Nordisk Investigational Site	Jefferson City	Missouri	United States	65109
47	Novo Nordisk Investigational Site	Kansas City	Missouri	United States	64106
48	Novo Nordisk Investigational Site	Billings	Montana	United States	59101
49	Novo Nordisk Investigational Site	Omaha	Nebraska	United States	68114
50	Novo Nordisk Investigational Site	Henderson	Nevada	United States	89052-2649
51	Novo Nordisk Investigational Site	Las Vegas	Nevada	United States	89148
52	Novo Nordisk Investigational Site	Nashua	New Hampshire	United States	03063
53	Novo Nordisk Investigational Site	Hamilton	New Jersey	United States	08690
54	Novo Nordisk Investigational Site	Albany	New York	United States	12206
55	Novo Nordisk Investigational Site	Harrison	New York	United States	10528
56	Novo Nordisk Investigational Site	Mineola	New York	United States	11501
57	Novo Nordisk Investigational Site	Syracuse	New York	United States	13210
58	Novo Nordisk Investigational Site	Asheville	North Carolina	United States	28803
59	Novo Nordisk Investigational Site	Greenville	North Carolina	United States	27834
60	Novo Nordisk Investigational Site	Morehead City	North Carolina	United States	28557
61	Novo Nordisk Investigational Site	Raleigh	North Carolina	United States	27609
62	Novo Nordisk Investigational Site	Toledo	Ohio	United States	43614
63	Novo Nordisk Investigational Site	Oklahoma City	Oklahoma	United States	73104
64	Novo Nordisk Investigational Site	Jenkintown	Pennsylvania	United States	19046
65	Novo Nordisk Investigational Site	Philadelphia	Pennsylvania	United States	19107
66	Novo Nordisk Investigational Site	Pittsburgh	Pennsylvania	United States	15224-2215
67	Novo Nordisk Investigational Site	Chattanooga	Tennessee	United States	37411
68	Novo Nordisk Investigational Site	Kingsport	Tennessee	United States	37660
69	Novo Nordisk Investigational Site	Amarillo	Texas	United States	79106
70	Novo Nordisk Investigational Site	Austin	Texas	United States	78731
71	Novo Nordisk Investigational Site	Austin	Texas	United States	78758
72	Novo Nordisk Investigational Site	Carrollton	Texas	United States	75007
73	Novo Nordisk Investigational Site	Dallas	Texas	United States	75231
74	Novo Nordisk Investigational Site	El Paso	Texas	United States	79912
75	Novo Nordisk Investigational Site	Houston	Texas	United States	77024
76	Novo Nordisk Investigational Site	Houston	Texas	United States	77079
77	Novo Nordisk Investigational Site	Katy	Texas	United States	77450
78	Novo Nordisk Investigational Site	Mesquite	Texas	United States	75149
79	Novo Nordisk Investigational Site	Richardson	Texas	United States	75080
80	Novo Nordisk Investigational Site	San Antonio	Texas	United States	78229
81	Novo Nordisk Investigational Site	Schertz	Texas	United States	78154
82	Novo Nordisk Investigational Site	Sugar Land	Texas	United States	77478
83	Novo Nordisk Investigational Site	Salt Lake City	Utah	United States	84102
84	Novo Nordisk Investigational Site	Salt Lake City	Utah	United States	84107
85	Novo Nordisk Investigational Site	Chesapeake	Virginia	United States	23321
86	Novo Nordisk Investigational Site	Norfolk	Virginia	United States	23510
87	Novo Nordisk Investigational Site	Federal Way	Washington	United States	98003
88	Novo Nordisk Investigational Site	Renton	Washington	United States	98057
89	Novo Nordisk Investigational Site	Richland	Washington	United States	99352
90	Novo Nordisk Investigational Site	Spokane	Washington	United States	99208
91	Novo Nordisk Investigational Site	Walla Walla	Washington	United States	99362-4445
92	Novo Nordisk Investigational Site	Milwaukee	Wisconsin	United States	53209
93	Novo Nordisk Investigational Site	Bialystok		Poland	15-435
94	Novo Nordisk Investigational Site	Gdansk		Poland	80-546
95	Novo Nordisk Investigational Site	Gdansk		Poland	80-858
96	Novo Nordisk Investigational Site	Szczecin		Poland	70-506
97	Novo Nordisk Investigational Site	Warszawa		Poland	04-736
98	Novo Nordisk Investigational Site	Zabrze		Poland	41-800
99	Novo Nordisk Investigational Site	Manati		Puerto Rico	00674

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: NCT02034513
• Other Study ID Numbers: NN1250-3995; U1111-1129-9668; 2012-001930-32
• First Posted: Jan 13, 2014
• Last Update Posted: Jan 2, 2019
• Last Verified: Dec 1, 2018

• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1; Insulin; Insulin, Globin Zinc; Insulin Glargine; Insulin Aspart

Study Results

Participant Flow

Recruitment Details	The trial was conducted at 90 sites in 2 countries, as follows: US: 84 sites, Poland: 6 sites.

Arm/Group Title	Insulin Degludec/Insulin Glargine (IDeg/IGlar)	Insulin Glargine/Insulin Degludec (IGlar/IDeg)
Arm/Group Description	Subjects received insulin degludec (IDeg) in treatment period 1 and insulin glargine (IGlar) in treatment period 2. Each treatment period consisted of a 16-week titration period and a 16-week maintenance period (total 32 weeks for each treatment period). IDeg and IGlar were administered subcutaneously (s.c.; under the skin) in the morning (from waking up to breakfast) or in the evening (from main evening meal to bedtime), as per randomisation and were to be taken once daily (OD) at the same time of day throughout the trial. To prevent an increased risk of hypoglycaemia in the first treatment month, the overall daily doses of IDeg and IGlar were reduced by 20% at the start of both the treatment periods. Doses of IDeg and IGlar were titrated individually. Titration of the dose was performed once weekly based on the lowest of 3 pre-breakfast self measured plasma glucose(SMPG) values measured on 3 consecutive days immediately prior to titration (fasting glycaemic target of 4.0-5.0 mmol/L)	Subjects received IGlar in treatment period 1 and IDeg in treatment period 2. Each treatment period consisted of a 16-week titration period and a 16-week maintenance period (total 32 weeks for each treatment period). IGlar and IDeg were administered s.c. in the morning (from waking up to breakfast) or in the evening (from main evening meal to bedtime), as per randomisation and were to be taken OD at the same time of day throughout the trial. To prevent an increased risk of hypoglycaemia in the first treatment month, the overall daily doses of IGlar and IDeg were reduced by 20% at the start of both the treatment periods. Doses of IGlar and IDeg were titrated individually. Titration of the dose was performed once weekly based on the lowest of 3 pre-breakfast SMPG values measured on 3 consecutive days immediately prior to titration (fasting glycaemic target of 4.0-5.0 mmol/L).
Period Title: Overall Study
STARTED	249	252
Exposed	249	251
COMPLETED	200	195
NOT COMPLETED	49	57

Baseline Characteristics

Arm/Group Title	Insulin Degludec/Insulin Glargine (IDeg/IGlar)	Insulin Glargine/Insulin Degludec (IGlar/IDeg)	Total
Arm/Group Description	Subjects received IDeg in treatment period 1 and IGlar in treatment period 2. Each treatment period consisted of a 16-week titration period and a 16-week maintenance period (total 32 weeks for each treatment period). IDeg and IGlar were administered s.c.in the morning (from waking up to breakfast) or in the evening (from main evening meal to bedtime), as per randomisation and were to be taken OD at the same time of day throughout the trial. To prevent an increased risk of hypoglycaemia in the first treatment month, the overall daily doses of IDeg and IGlar were reduced by 20% at the start of both the treatment periods. Doses of IDeg and IGlar were titrated individually. Titration of the dose was performed once weekly based on the lowest of 3 pre-breakfast SMPG values measured on 3 consecutive days immediately prior to titration fasting glycaemic target of 4.0-5.0 mmol/L).	Subjects received IGlar in treatment period 1 and IDeg in treatment period 2. Each treatment period consisted of a 16-week titration period and a 16-week maintenance period (total 32 weeks for each treatment period). IGlar and IDeg were administered s.c. in the morning (from waking up to breakfast) or in the evening (from main evening meal to bedtime), as per randomisation and were to be taken OD at the same time of day throughout the trial. To prevent an increased risk of hypoglycaemia in the first treatment month, the overall daily doses of IGlar and IDeg were reduced by 20% at the start of both the treatment periods. Doses of IGlar and IDeg were titrated individually. Titration of the dose was performed once weekly based on the lowest of 3 pre-breakfast SMPG values measured on 3 consecutive days immediately prior to titration (fasting glycaemic target of 4.0-5.0 mmol/L).	Total of all reporting groups
Overall Participants	249	252	501
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.4 (13.7)	46.4 (14.6)	45.9 (14.2)
Sex: Female, Male (Count of Participants)
Female	123 49.4%	109 43.3%	232 46.3%
Male	126 50.6%	143 56.7%	269 53.7%
Glycosylated hemoglobin (HbA1c) (Percentage of HbA1c) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percentage of HbA1c]	7.7 (1.0)	7.5 (1.0)	7.6 (1.0)
Fasting plasma glucose (FPG) (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	165.1 (77.3)	174.4 (81.7)	169.8 (79.6)

Outcome Measures

1. Primary Outcome

Title	Number of Treatment Emergent Severe or BG (Blood Glucose) Confirmed Symptomatic Hypoglycaemic Episodes During the Maintenance Period
Description	Severe or blood glucose (BG) confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe and/or BG confirmed by a plasma glucose value of <3.1 mmol/L (56 mg/dL), with symptoms consistent with hypoglycaemia. Treatment emergent hypoglycaemic episode was defined as an event with onset date on or after the first day of exposure to randomised treatment and no later than the last day of randomised treatment. Maintenance period: 16 weeks of treatment, in each treatment period (Week 16-32 and Week 48-64).
Time Frame	A 16-week treatment period.

Outcome Measure Data

Analysis Population Description

The trial followed a cross over design. Descriptive analysis was based on the safety analysis set (SAS: subjects receiving at least 1 dose of the investigational product, IDeg or its comparator, IGlar). Number of subjects analysed=subjects in the SAS, who were exposed in at least one maintenance period.

Arm/Group Title	Insulin Degludec (IDeg)	Insulin Glargine (IGlar)
Arm/Group Description	Subjects received IDeg in treatment period 1 (from treatment sequence IDeg/IGlar) and in treatment period 2 (from treatment sequence IGlar/IDeg). Each treatment period consisted of a 16-week titration period and a 16-week maintenance period (total 32 weeks for each treatment period). IDeg was administered s.c. in the morning (from waking up to breakfast) or in the evening (from main evening meal to bedtime), as per randomisation and was to be taken OD at the same time of day throughout the trial. To prevent an increased risk of hypoglycaemia in the first treatment month, the overall daily doses of IDeg were reduced by 20% at the start of both the treatment periods. Doses of IDeg were titrated individually. Titration of the dose was performed once weekly based on the lowest of 3 pre-breakfast SMPG values measured on 3 consecutive days immediately prior to titration (fasting glycaemic target of 4.0-5.0 mmol/L).	Subjects received IGlar in treatment period 1 (from treatment sequence IGlar/IDeg) and in treatment period 2 (from treatment sequence IDeg/IGlar). Each treatment period consisted of a 16-week titration period and a 16-week maintenance period (total 32 weeks for each treatment period). IGlar was administered s.c. in the morning (from waking up to breakfast) or in the evening (from main evening meal to bedtime), as per randomisation and was to be taken OD at the same time of day throughout the trial. To prevent an increased risk of hypoglycaemia in the first treatment month, the overall daily doses of IGlar were reduced by 20% at the start of both the treatment periods. Doses of IGlar were titrated individually. Titration of the dose was performed once weekly based on the lowest of 3 pre-breakfast SMPG values measured on 3 consecutive days immediately prior to titration (fasting glycaemic target of 4.0-5.0 mmol/L).
Measure Participants	418	422
Number [Event]	2772	3126

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Degludec (IDeg), Insulin Glargine (IGlar)
	Comments	Statistical analysis was performed on the FAS. Number of subjects analysed=subjects in the FAS, who were exposed in at least one maintenance period. Stepwise hierarchical testing procedure was applied for confirmatory endpoints: Step 1: Number of treatment-emergent severe or BG confirmed symptomatic hypoglycaemic episodes during the maintenance period.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority was considered confirmed if the 95% confidence interval for the rate ratio (IDeg/IGlar) was ≤1.10 or equivalently if the p-value for the 1-sided test of H0: RR >1.10 against HA: RR ≤1.10 was less than 2.5%, where RR is the estimated rate ratio IDeg/IGlar.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Poisson
	Comments
Method of Estimation	Estimation Parameter	Treatment ratio
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 95%; 0.85 to 0.94
	Parameter Dispersion	Type: Value:
	Estimation Comments	If non-inferiority was confirmed the superiority of IDeg/IGlar was investigated outside of the test hierarchy. Superiority was considered confirmed if the upper bound of the 2-sided 95% confidence interval was <1.00.

2. Secondary Outcome

Title	Number of Treatment Emergent Severe or BG Confirmed Symptomatic Nocturnal Hypoglycaemic Episodes During the Maintenance Period
Description	Severe or BG confirmed symptomatic nocturnal hypoglycaemic episodes were defined as episodes that were severe and/or BG confirmed by a plasma glucose value of <3.1 mmol/L (56 mg/dL), with symptoms consistent with hypoglycaemia and with time of onset between 00:01 and 05.59 a.m., both inclusive. Treatment emergent hypoglycaemic episode was defined as an event with onset date on or after the first day of exposure to randomised treatment and no later than the last day of randomised treatment.
Time Frame	After 16 weeks of treatment, in each treatment period (Week 16-32 and Week 48-64)

Outcome Measure Data

Analysis Population Description

The trial followed a cross over design. Descriptive analysis was based on the SAS. Number of subjects analysed=subjects in the SAS, who were exposed in at least one maintenance period.

Arm/Group Title	Insulin Degludec (IDeg)	Insulin Glargine (IGlar)
Arm/Group Description	Subjects received IDeg in treatment period 1 (from treatment sequence IDeg/IGlar) and in treatment period 2 (from treatment sequence IGlar/IDeg). Each treatment period consisted of a 16-week titration period and a 16-week maintenance period (total 32 weeks for each treatment period). IDeg was administered s.c. in the morning (from waking up to breakfast) or in the evening (from main evening meal to bedtime), as per randomisation and was to be taken OD at the same time of day throughout the trial. To prevent an increased risk of hypoglycaemia in the first treatment month, the overall daily doses of IDeg were reduced by 20% at the start of both the treatment periods. Doses of IDeg were titrated individually. Titration of the dose was performed once weekly based on the lowest of 3 pre-breakfast SMPG values measured on 3 consecutive days immediately prior to titration (fasting glycaemic target of 4.0-5.0 mmol/L).	Subjects received IGlar in treatment period 1 (from treatment sequence IGlar/IDeg) and in treatment period 2 (from treatment sequence IDeg/IGlar). Each treatment period consisted of a 16-week titration period and a 16-week maintenance period (total 32 weeks for each treatment period). IGlar was administered s.c. in the morning (from waking up to breakfast) or in the evening (from main evening meal to bedtime), as per randomisation and was to be taken OD at the same time of day throughout the trial. To prevent an increased risk of hypoglycaemia in the first treatment month, the overall daily doses of IGlar were reduced by 20% at the start of both the treatment periods. Doses of IGlar were titrated individually. Titration of the dose was performed once weekly based on the lowest of 3 pre-breakfast SMPG values measured on 3 consecutive days immediately prior to titration (fasting glycaemic target of 4.0-5.0 mmol/L).
Measure Participants	418	422
Number [Event]	349	544

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Degludec (IDeg), Insulin Glargine (IGlar)
	Comments	Statistical analysis was performed on the FAS. Number of subjects analysed=subjects in the FAS, who were exposed in at least one maintenance period. Stepwise hierarchical testing procedure was applied for confirmatory endpoints: Step 2: Number of treatment-emergent severe or BG confirmed symptomatic nocturnal hypoglycaemic episodes during the maintenance period.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority was considered confirmed if the 95% confidence interval for the rate ratio (IDeg/IGlar) was ≤1.10 or equivalently if the p-value for the 1-sided test of H0: RR >1.10 against HA: RR ≤1.10 was less than 2.5%, where RR is the estimated rate ratio IDeg/IGlar.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Poisson
	Comments
Method of Estimation	Estimation Parameter	Treatment ratio
	Estimated Value	0.64
	Confidence Interval	(2-Sided) 95%; 0.56 to 0.73
	Parameter Dispersion	Type: Value:
	Estimation Comments	If non-inferiority was confirmed the superiority of IDeg/IGlar was investigated outside of the test hierarchy. Superiority was considered confirmed if the upper bound of the 2-sided 95% confidence interval was <1.00.

3. Secondary Outcome

Title	Proportion of Subjects With One or More Severe Hypoglycaemic Episodes During the Maintenance Period
Description	Percentage of subjects who experienced one or more severe hypoglycaemic episodes during the maintenance period. Severe hypoglycaemia (according to the American Diabetes Association 2013 definition): A hypoglycaemic episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. Plasma glucose values may not be available during an event, but neurological recovery following the return of plasma glucose to normal is considered sufficient evidence that the event was induced by a low plasma glucose concentration.
Time Frame	After 16 weeks of treatment, in each treatment period (Week 16-32 and Week 48-64)

Outcome Measure Data

Analysis Population Description

The trial followed a cross over design. Descriptive analysis was based on the SAS. Number of subjects analysed=subjects in the SAS, who were exposed in at least one maintenance period.

Arm/Group Title	Insulin Degludec (IDeg)	Insulin Glargine (IGlar)
Arm/Group Description	Subjects received IDeg in treatment period 1 (from treatment sequence IDeg/IGlar) and in treatment period 2 (from treatment sequence IGlar/IDeg). Each treatment period consisted of a 16-week titration period and a 16-week maintenance period (total 32 weeks for each treatment period). IDeg was administered s.c. in the morning (from waking up to breakfast) or in the evening (from main evening meal to bedtime), as per randomisation and was to be taken OD at the same time of day throughout the trial. To prevent an increased risk of hypoglycaemia in the first treatment month, the overall daily doses of IDeg were reduced by 20% at the start of both the treatment periods. Doses of IDeg were titrated individually. Titration of the dose was performed once weekly based on the lowest of 3 pre-breakfast SMPG values measured on 3 consecutive days immediately prior to titration (fasting glycaemic target of 4.0-5.0 mmol/L).	Subjects received IGlar in treatment period 1 (from treatment sequence IGlar/IDeg) and in treatment period 2 (from treatment sequence IDeg/IGlar). Each treatment period consisted of a 16-week titration period and a 16-week maintenance period (total 32 weeks for each treatment period). IGlar was administered s.c. in the morning (from waking up to breakfast) or in the evening (from main evening meal to bedtime), as per randomisation and was to be taken OD at the same time of day throughout the trial. To prevent an increased risk of hypoglycaemia in the first treatment month, the overall daily doses of IGlar were reduced by 20% at the start of both the treatment periods. Doses of IGlar were titrated individually. Titration of the dose was performed once weekly based on the lowest of 3 pre-breakfast SMPG values measured on 3 consecutive days immediately prior to titration (fasting glycaemic target of 4.0-5.0 mmol/L).
Measure Participants	418	422
Number [Percentage of subjects]	10.3	17.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Degludec (IDeg), Insulin Glargine (IGlar)
	Comments	Statistical analysis was performed on the FAS. Number of subjects analysed=subjects in the FAS, who were exposed in both the maintenance periods. Stepwise hierarchical testing procedure was applied for confirmatory endpoints: Step 3: Proportion of subjects with one or more severe hypoglycaemic episodes during the maintenance period.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0016
	Comments	Superiority was confirmed if the p-value was less than 0.025.
	Method	McNemar
	Comments

4. Secondary Outcome

Title	Incidence of Treatment Emergent Adverse Events
Description	Treatment emergent adverse event was defined as an event with onset date on or after the first day of exposure to randomised treatment and no later than the last day of randomised treatment.
Time Frame	During 32 weeks of treatment for each treatment period

Outcome Measure Data

Analysis Population Description

The trial followed a cross over design. Results are based on the SAS.

Arm/Group Title	Insulin Degludec (IDeg)	Insulin Glargine (IGlar)
Arm/Group Description	Subjects received IDeg in treatment period 1 (from treatment sequence IDeg/IGlar) and in treatment period 2 (from treatment sequence IGlar/IDeg). Each treatment period consisted of a 16-week titration period and a 16-week maintenance period (total 32 weeks for each treatment period). IDeg was administered s.c. in the morning (from waking up to breakfast) or in the evening (from main evening meal to bedtime), as per randomisation and was to be taken OD at the same time of day throughout the trial. To prevent an increased risk of hypoglycaemia in the first treatment month, the overall daily doses of IDeg were reduced by 20% at the start of both the treatment periods. Doses of IDeg were titrated individually. Titration of the dose was performed once weekly based on the lowest of 3 pre-breakfast SMPG values measured on 3 consecutive days immediately prior to titration (fasting glycaemic target of 4.0-5.0 mmol/L).	Subjects received IGlar in treatment period 1 (from treatment sequence IGlar/IDeg) and in treatment period 2 (from treatment sequence IDeg/IGlar). Each treatment period consisted of a 16-week titration period and a 16-week maintenance period (total 32 weeks for each treatment period). IGlar was administered s.c. in the morning (from waking up to breakfast) or in the evening (from main evening meal to bedtime), as per randomisation and was to be taken OD at the same time of day throughout the trial. To prevent an increased risk of hypoglycaemia in the first treatment month, the overall daily doses of IGlar were reduced by 20% at the start of both the treatment periods. Doses of IGlar were titrated individually. Titration of the dose was performed once weekly based on the lowest of 3 pre-breakfast SMPG values measured on 3 consecutive days immediately prior to titration (fasting glycaemic target of 4.0-5.0 mmol/L).
Measure Participants	454	460
Number [Event]	925	937

5. Secondary Outcome

Title	Change From Baseline in HbA1c (Glycosylated Haemoglobin)
Description	Change from baseline in HbA1c (glycosylated haemoglobin) at week 32 (treatment period 1) and at week 64 (treatment period 2). Week 32 HbA1c absolute value was considered as baseline for calculating change from baseline in HbA1c at week 64.
Time Frame	Week 32, Week 64

Outcome Measure Data

Analysis Population Description

Both descriptive analysis and statistical analysis were based on the FAS. Here, 'n' specifies the number of subjects with available data at specified time-point.

Arm/Group Title	Insulin Degludec/Insulin Glargine (IDeg/IGlar)	Insulin Glargine/Insulin Degludec (IGlar/IDeg)
Arm/Group Description	Subjects received IDeg in treatment period 1 and IGlar in treatment period 2. Each treatment period consisted of a 16-week titration period and a 16-week maintenance period (total 32 weeks for each treatment period). IDeg and IGlar were administered s.c.in the morning (from waking up to breakfast) or in the evening (from main evening meal to bedtime), as per randomisation and were to be taken OD at the same time of day throughout the trial. To prevent an increased risk of hypoglycaemia in the first treatment month, the overall daily doses of IDeg and IGlar were reduced by 20% at the start of both the treatment periods. Doses of IDeg and IGlar were titrated individually. Titration of the dose was performed once weekly based on the lowest of 3 pre-breakfast SMPG values measured on 3 consecutive days immediately prior to titration fasting glycaemic target of 4.0-5.0 mmol/L).	Subjects received IGlar in treatment period 1 and IDeg in treatment period 2. Each treatment period consisted of a 16-week titration period and a 16-week maintenance period (total 32 weeks for each treatment period). IGlar and IDeg were administered s.c. in the morning (from waking up to breakfast) or in the evening (from main evening meal to bedtime), as per randomisation and were to be taken OD at the same time of day throughout the trial. To prevent an increased risk of hypoglycaemia in the first treatment month, the overall daily doses of IGlar and IDeg were reduced by 20% at the start of both the treatment periods. Doses of IGlar and IDeg were titrated individually. Titration of the dose was performed once weekly based on the lowest of 3 pre-breakfast SMPG values measured on 3 consecutive days immediately prior to titration (fasting glycaemic target of 4.0-5.0 mmol/L).
Measure Participants	249	252
week 32 (n=209, 205)	-0.73 (0.89)	-0.66 (0.76)
week 64 (n=203, 199)	0.04 (0.51)	0.17 (0.64)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Degludec (IDeg), Insulin Glargine (IGlar)
	Comments	Change from baseline in HbA1c at week 32 (treatment period 1). Before testing the primary endpoint, the secondary supportive efficacy endpoint "Change from baseline in HbA1c after 32 weeks of treatment" was tested for non-inferiority as a prerequisite for testing the primary endpoint. Analysis was based on mixed model for repeated measurement (MMRM); treatment, sex, region, pre-trial insulin treatment regimen, visit and dosing time were fixed effects, and age and baseline HbA1c were covariates.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority was considered confirmed if the upper bound of the two-sided 95% confidence interval was below or equal to 0.40%. Comparison groups: IDeg versus IGlar. Number of subjects included in analysis is 437 (n=220 for IDeg and n=217 for IGlar).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment contrast
	Estimated Value	0.03
	Confidence Interval	(2-Sided) 95%; -0.10 to 0.15
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Insulin Degludec (IDeg), Insulin Glargine (IGlar)
	Comments	Change from baseline in HbA1c at week 64 (treatment period 2). The baseline values are week 32 values. Before the primary endpoint was tested, the secondary supportive efficacy endpoint "Change from baseline in HbA1c after 32 weeks of treatment" was tested for non-inferiority as prerequisite for testing the primary endpoint. Analysis was based on MMRM; treatment, sex, region, pre-trial insulin treatment regimen, visit and dosing time were fixed effects, and age and baseline HbA1c were covariates
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority was considered confirmed if the upper bound of the two-sided 95% confidence interval was below or equal to 0.40%. Comparison groups: IDeg versus IGlar. Number of subjects included in analysis is 410 (n=202 for IDeg and n=208 for IGlar).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment contrast
	Estimated Value	0.11
	Confidence Interval	(2-Sided) 95%; -0.00 to 0.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	FPG (Fasting Plasma Glucose)
Description	Fasting plasma glucose values at week 32 and week 64.
Time Frame	Week 32 and Week 64

Outcome Measure Data

Analysis Population Description

Results are based on the FAS. Here, 'n' specifies the number of subjects with available data at specified time-point.

Arm/Group Title	Insulin Degludec/Insulin Glargine (IDeg/IGlar)	Insulin Glargine/Insulin Degludec (IGlar/IDeg)
Arm/Group Description	Subjects received IDeg in treatment period 1 and IGlar in treatment period 2. Each treatment period consisted of a 16-week titration period and a 16-week maintenance period (total 32 weeks for each treatment period). IDeg and IGlar were administered s.c.in the morning (from waking up to breakfast) or in the evening (from main evening meal to bedtime), as per randomisation and were to be taken OD at the same time of day throughout the trial. To prevent an increased risk of hypoglycaemia in the first treatment month, the overall daily doses of IDeg and IGlar were reduced by 20% at the start of both the treatment periods. Doses of IDeg and IGlar were titrated individually. Titration of the dose was performed once weekly based on the lowest of 3 pre-breakfast SMPG values measured on 3 consecutive days immediately prior to titration fasting glycaemic target of 4.0-5.0 mmol/L).	Subjects received IGlar in treatment period 1 and IDeg in treatment period 2. Each treatment period consisted of a 16-week titration period and a 16-week maintenance period (total 32 weeks for each treatment period). IGlar and IDeg were administered s.c. in the morning (from waking up to breakfast) or in the evening (from main evening meal to bedtime), as per randomisation and were to be taken OD at the same time of day throughout the trial. To prevent an increased risk of hypoglycaemia in the first treatment month, the overall daily doses of IGlar and IDeg were reduced by 20% at the start of both the treatment periods. Doses of IGlar and IDeg were titrated individually. Titration of the dose was performed once weekly based on the lowest of 3 pre-breakfast SMPG values measured on 3 consecutive days immediately prior to titration (fasting glycaemic target of 4.0-5.0 mmol/L).
Measure Participants	249	252
week 32 (n=208, 204)	7.45 (3.57)	8.12 (3.56)
week 64 (n=203, 201)	8.62 (4.24)	7.54 (3.68)

Adverse Events

Time Frame	From the first day of exposure to randomised treatment and no later than the last day of randomised treatment (64 weeks).
Adverse Event Reporting Description	Subjects in the SAS contributed to the evaluation of adverse events. The following displayed "number of subjects at risk"=454 and 460 for IDeg and IGlar, respectively (i.e, out of a total of 500 exposed subjects, 454 received IDeg and 460 received IGlar in a cross-over manner in 2 treatment periods.
Arm/Group Title	Insulin Degludec (IDeg)		Insulin Glargine (IGlar)
Arm/Group Description	Subjects received IDeg in treatment period 1 (from treatment sequence IDeg/IGlar) and in treatment period 2 (from treatment sequence IGlar/IDeg). Each treatment period consisted of a 16-week titration period and a 16-week maintenance period (total 32 weeks for each treatment period). IDeg was administered s.c. in the morning (from waking up to breakfast) or in the evening (from main evening meal to bedtime), as per randomisation and was to be taken OD at the same time of day throughout the trial. To prevent an increased risk of hypoglycaemia in the first treatment month, the overall daily doses of IDeg were reduced by 20% at the start of both the treatment periods. Doses of IDeg were titrated individually. Titration of the dose was performed once weekly based on the lowest of 3 pre-breakfast SMPG values measured on 3 consecutive days immediately prior to titration (fasting glycaemic target of 4.0-5.0 mmol/L).		Subjects received IGlar in treatment period 1 (from treatment sequence IGlar/IDeg) and in treatment period 2 (from treatment sequence IDeg/IGlar). Each treatment period consisted of a 16-week titration period and a 16-week maintenance period (total 32 weeks for each treatment period). IGlar was administered s.c. in the morning (from waking up to breakfast) or in the evening (from main evening meal to bedtime), as per randomisation and was to be taken OD at the same time of day throughout the trial. To prevent an increased risk of hypoglycaemia in the first treatment month, the overall daily doses of IGlar were reduced by 20% at the start of both the treatment periods. Doses of IGlar were titrated individually. Titration of the dose was performed once weekly based on the lowest of 3 pre-breakfast SMPG values measured on 3 consecutive days immediately prior to titration (fasting glycaemic target of 4.0-5.0 mmol/L).
All Cause Mortality
	Insulin Degludec (IDeg)		Insulin Glargine (IGlar)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Insulin Degludec (IDeg)		Insulin Glargine (IGlar)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	58/454 (12.8%)		70/460 (15.2%)
Cardiac disorders
Acute coronary syndrome	0/454 (0%)	0	1/460 (0.2%)	1
Acute myocardial infarction	1/454 (0.2%)	1	1/460 (0.2%)	1
Supraventricular tachycardia	0/454 (0%)	0	1/460 (0.2%)	1
Ventricular tachycardia	1/454 (0.2%)	1	0/460 (0%)	0
Wolff-Parkinson-White syndrome	0/454 (0%)	0	1/460 (0.2%)	1
Eye disorders
Optic ischaemic neuropathy	0/454 (0%)	0	1/460 (0.2%)	1
Gastrointestinal disorders
Abdominal pain	0/454 (0%)	0	1/460 (0.2%)	1
Ascites	0/454 (0%)	0	1/460 (0.2%)	1
Colitis	0/454 (0%)	0	1/460 (0.2%)	1
Constipation	0/454 (0%)	0	1/460 (0.2%)	1
Gastrointestinal haemorrhage	1/454 (0.2%)	1	0/460 (0%)	0
Ileus	0/454 (0%)	0	1/460 (0.2%)	1
Impaired gastric emptying	1/454 (0.2%)	1	1/460 (0.2%)	1
Large intestine polyp	1/454 (0.2%)	1	0/460 (0%)	0
Pancreatitis	0/454 (0%)	0	1/460 (0.2%)	1
Vomiting	1/454 (0.2%)	1	2/460 (0.4%)	2
General disorders
Non-cardiac chest pain	1/454 (0.2%)	1	0/460 (0%)	0
Pyrexia	0/454 (0%)	0	1/460 (0.2%)	1
Hepatobiliary disorders
Biliary dyskinesia	1/454 (0.2%)	1	0/460 (0%)	0
Cholelithiasis	1/454 (0.2%)	1	0/460 (0%)	0
Infections and infestations
Bacterial sepsis	1/454 (0.2%)	1	0/460 (0%)	0
Cellulitis	2/454 (0.4%)	3	0/460 (0%)	0
Clostridium difficile colitis	1/454 (0.2%)	1	0/460 (0%)	0
Fungal skin infection	0/454 (0%)	0	1/460 (0.2%)	1
Influenza	1/454 (0.2%)	1	0/460 (0%)	0
Osteomyelitis	1/454 (0.2%)	1	1/460 (0.2%)	1
Pneumonia	2/454 (0.4%)	2	3/460 (0.7%)	3
Pneumonia bacterial	1/454 (0.2%)	1	0/460 (0%)	0
Sepsis	1/454 (0.2%)	1	0/460 (0%)	0
Injury, poisoning and procedural complications
Accidental overdose	2/454 (0.4%)	2	3/460 (0.7%)	3
Fall	2/454 (0.4%)	2	0/460 (0%)	0
Gun shot wound	1/454 (0.2%)	1	0/460 (0%)	0
Overdose	0/454 (0%)	0	1/460 (0.2%)	1
Pelvic fracture	0/454 (0%)	0	1/460 (0.2%)	1
Respiratory fume inhalation disorder	1/454 (0.2%)	1	0/460 (0%)	0
Road traffic accident	0/454 (0%)	0	1/460 (0.2%)	1
Tibia fracture	1/454 (0.2%)	1	0/460 (0%)	0
Metabolism and nutrition disorders
Dehydration	0/454 (0%)	0	1/460 (0.2%)	1
Diabetic ketoacidosis	2/454 (0.4%)	4	3/460 (0.7%)	3
Hypoglycaemia	17/454 (3.7%)	32	33/460 (7.2%)	47
Musculoskeletal and connective tissue disorders
Intervertebral disc degeneration	0/454 (0%)	0	1/460 (0.2%)	1
Intervertebral disc displacement	0/454 (0%)	0	1/460 (0.2%)	1
Lumbar spinal stenosis	1/454 (0.2%)	1	0/460 (0%)	0
Rhabdomyolysis	0/454 (0%)	0	1/460 (0.2%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer in situ	1/454 (0.2%)	1	0/460 (0%)	0
Papillary thyroid cancer	1/454 (0.2%)	1	0/460 (0%)	0
Uterine leiomyoma	2/454 (0.4%)	2	0/460 (0%)	0
Nervous system disorders
Cerebrovascular accident	1/454 (0.2%)	1	0/460 (0%)	0
Dizziness	0/454 (0%)	0	1/460 (0.2%)	1
Headache	0/454 (0%)	0	1/460 (0.2%)	1
Hypoglycaemic coma	0/454 (0%)	0	1/460 (0.2%)	1
Hypoglycaemic seizure	3/454 (0.7%)	5	5/460 (1.1%)	5
Hypoglycaemic unconsciousness	18/454 (4%)	23	19/460 (4.1%)	24
Loss of consciousness	0/454 (0%)	0	1/460 (0.2%)	1
Multiple sclerosis	0/454 (0%)	0	1/460 (0.2%)	1
Optic neuritis	0/454 (0%)	0	1/460 (0.2%)	1
Syncope	0/454 (0%)	0	1/460 (0.2%)	1
Psychiatric disorders
Mental status changes	0/454 (0%)	0	1/460 (0.2%)	1
Schizophrenia	1/454 (0.2%)	1	0/460 (0%)	0
Renal and urinary disorders
Calculus ureteric	0/454 (0%)	0	1/460 (0.2%)	1
Respiratory, thoracic and mediastinal disorders
Pneumothorax	1/454 (0.2%)	1	0/460 (0%)	0
Surgical and medical procedures
Pancreas transplant	1/454 (0.2%)	1	0/460 (0%)	0
Vascular disorders
Haematoma	1/454 (0.2%)	1	0/460 (0%)	0
Other (Not Including Serious) Adverse Events
	Insulin Degludec (IDeg)		Insulin Glargine (IGlar)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	97/454 (21.4%)		97/460 (21.1%)
Infections and infestations
Nasopharyngitis	68/454 (15%)	92	61/460 (13.3%)	73
Upper respiratory tract infection	29/454 (6.4%)	34	39/460 (8.5%)	41

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

At the end of the trial, one or more scientific publications may be prepared collaboratively by the investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for up to 60 days to protect intellectual property.