SWITCH 2: A Trial Comparing the Safety and Efficacy of Insulin Degludec and Insulin Glargine, With or Without OADs in Subjects With Type 2 Diabetes

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02030600
• Collaborator: (none)
• Enrollment: 721
• Locations: 166
• Arms: 2
• Actual Duration (Months): 22.9
• Patients Per Site: 4.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This trial is conducted in 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) with or without OADs (oral anti-diabetic drugs) excluding SUs (sulfonylureas)/glinides in subjects with type 2 diabetes.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 721 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, With or Without OADs in Subjects With Type 2 Diabetes (SWITCH 2)
• Actual Study Start Date: Jan 6, 2014
• Actual Primary Completion Date: Dec 4, 2015
• Actual Study Completion Date: Dec 4, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IDeg OD ± OADs followed by IGlar OD ± OADs The trial includes two 32-week treatment periods in a cross-over design. Total trial duration for the individual subjects will be up to 67 weeks.	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.
Active Comparator: IGlar OD ± OADs followed by IDeg OD ± OADs The trial includes two 32-week treatment periods in a cross-over design. Total trial duration for the individual subjects will be up to 67 weeks.	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.

Outcome Measures

Primary Outcome Measures

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

   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 <56 mg/dL (3.1 mmol/L), 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.

Secondary Outcome Measures

1. Number of Treatment Emergent Severe or BG Confirmed Symptomatic Nocturnal Hypoglycaemic Episode 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 <56 mg/dL (3.1 mmol/L), 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 value was considered as baseline for calculating change from baseline in HbA1c at week 64.

5. FPG (Fasting Plasma Glucose) [week 32, 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: - Male or female, age at least 18 years at the time of signing informed consent - Subjects fulfilling at least one of the below criteria: a) Experienced at least one severe hypoglycaemic episode within 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) by central laboratory analysis, c) Hypoglycaemic symptom unawareness, d) Exposed to insulin for more than 5 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) - Type 2 diabetes mellitus (diagnosed clinically) for at least 26 weeks prior to Visit 1 - Current treatment with any basal insulin (OD or BID) ± any combination of OADs (metformin, DPP-4 inhibitor, alpha-glucosidase inhibitor, thiazolidinediones, and SGLT2-inhibitor) for 26 weeks or longer prior to Visit 1 For subjects on BID the total daily dose should be below 75 units - HbA1c (glycosylated haemoglobin) below or equal to 9.5 % by central laboratory analysis - BMI (body mass index) below or equal to 45 kg/m}2 Exclusion Criteria: - Treatment with a bolus insulin separately or contained in an insulin mix product within the last 26 weeks prior to Visit 1 - Use of any other anti-diabetic agent(s) 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	Birmingham	Alabama	United States	35216
3	Novo Nordisk Investigational Site	Haleyville	Alabama	United States	35565-1719
4	Novo Nordisk Investigational Site	Montgomery	Alabama	United States	36106
5	Novo Nordisk Investigational Site	Tuscumbia	Alabama	United States	35674
6	Novo Nordisk Investigational Site	Chandler	Arizona	United States	85224
7	Novo Nordisk Investigational Site	Phoenix	Arizona	United States	85050
8	Novo Nordisk Investigational Site	Tucson	Arizona	United States	85704
9	Novo Nordisk Investigational Site	Little Rock	Arkansas	United States	72205
10	Novo Nordisk Investigational Site	Costa Mesa	California	United States	92626
11	Novo Nordisk Investigational Site	Downey	California	United States	90242
12	Novo Nordisk Investigational Site	El Cajon	California	United States	92020
13	Novo Nordisk Investigational Site	Fresno	California	United States	93702
14	Novo Nordisk Investigational Site	Fresno	California	United States	93720
15	Novo Nordisk Investigational Site	Hawaiian Gardens	California	United States	90716
16	Novo Nordisk Investigational Site	Huntington Park	California	United States	90255
17	Novo Nordisk Investigational Site	Lincoln	California	United States	95648
18	Novo Nordisk Investigational Site	Long Beach	California	United States	90807
19	Novo Nordisk Investigational Site	Montclair	California	United States	91763
20	Novo Nordisk Investigational Site	North Hollywood	California	United States	91606
21	Novo Nordisk Investigational Site	Northridge	California	United States	91325
22	Novo Nordisk Investigational Site	Pomona	California	United States	91766-2007
23	Novo Nordisk Investigational Site	Poway	California	United States	92064
24	Novo Nordisk Investigational Site	Rancho Cucamonga	California	United States	91730-3063
25	Novo Nordisk Investigational Site	Rialto	California	United States	92376
26	Novo Nordisk Investigational Site	Roseville	California	United States	95661
27	Novo Nordisk Investigational Site	San Diego	California	United States	92111
28	Novo Nordisk Investigational Site	Santa Monica	California	United States	90404
29	Novo Nordisk Investigational Site	Tarzana	California	United States	91356-3551
30	Novo Nordisk Investigational Site	Torrance	California	United States	90502
31	Novo Nordisk Investigational Site	Tustin	California	United States	92780
32	Novo Nordisk Investigational Site	Colorado Springs	Colorado	United States	80910
33	Novo Nordisk Investigational Site	Golden	Colorado	United States	80401
34	Novo Nordisk Investigational Site	Newark	Delaware	United States	19713
35	Novo Nordisk Investigational Site	Bradenton	Florida	United States	34201
36	Novo Nordisk Investigational Site	Chiefland	Florida	United States	32626
37	Novo Nordisk Investigational Site	Clearwater	Florida	United States	33756
38	Novo Nordisk Investigational Site	Clearwater	Florida	United States	33765
39	Novo Nordisk Investigational Site	Cooper City	Florida	United States	33024
40	Novo Nordisk Investigational Site	Doral	Florida	United States	33166
41	Novo Nordisk Investigational Site	Hialeah	Florida	United States	33012
42	Novo Nordisk Investigational Site	Hialeah	Florida	United States	33013
43	Novo Nordisk Investigational Site	Jacksonville	Florida	United States	32204
44	Novo Nordisk Investigational Site	Jacksonville	Florida	United States	32216
45	Novo Nordisk Investigational Site	Jacksonville	Florida	United States	32256
46	Novo Nordisk Investigational Site	Jacksonville	Florida	United States	32277
47	Novo Nordisk Investigational Site	Miami Springs	Florida	United States	33166
48	Novo Nordisk Investigational Site	Miami	Florida	United States	33130
49	Novo Nordisk Investigational Site	Miami	Florida	United States	33155
50	Novo Nordisk Investigational Site	Miami	Florida	United States	33156
51	Novo Nordisk Investigational Site	Miami	Florida	United States	33165
52	Novo Nordisk Investigational Site	Miami	Florida	United States	33174
53	Novo Nordisk Investigational Site	Miami	Florida	United States	33175
54	Novo Nordisk Investigational Site	Miami	Florida	United States	33186
55	Novo Nordisk Investigational Site	Miramar	Florida	United States	33027
56	Novo Nordisk Investigational Site	New Port Richey	Florida	United States	34652
57	Novo Nordisk Investigational Site	Ocala	Florida	United States	34470
58	Novo Nordisk Investigational Site	Orlando	Florida	United States	32801
59	Novo Nordisk Investigational Site	Panama City	Florida	United States	32401
60	Novo Nordisk Investigational Site	Pembroke Pines	Florida	United States	33026
61	Novo Nordisk Investigational Site	Tampa	Florida	United States	33607
62	Novo Nordisk Investigational Site	Tampa	Florida	United States	33619
63	Novo Nordisk Investigational Site	Perry	Georgia	United States	31069
64	Novo Nordisk Investigational Site	Champaign	Illinois	United States	61821
65	Novo Nordisk Investigational Site	Chicago	Illinois	United States	60611
66	Novo Nordisk Investigational Site	Evansville	Indiana	United States	47714
67	Novo Nordisk Investigational Site	Muncie	Indiana	United States	47304
68	Novo Nordisk Investigational Site	West Des Moines	Iowa	United States	50265
69	Novo Nordisk Investigational Site	Lenexa	Kansas	United States	66219
70	Novo Nordisk Investigational Site	Newton	Kansas	United States	67114
71	Novo Nordisk Investigational Site	Lexington	Kentucky	United States	40502
72	Novo Nordisk Investigational Site	Lexington	Kentucky	United States	40503
73	Novo Nordisk Investigational Site	Louisville	Kentucky	United States	40213
74	Novo Nordisk Investigational Site	Paducah	Kentucky	United States	42003
75	Novo Nordisk Investigational Site	New Orleans	Louisiana	United States	70119
76	Novo Nordisk Investigational Site	Shreveport	Louisiana	United States	71105
77	Novo Nordisk Investigational Site	Brockton	Massachusetts	United States	02301
78	Novo Nordisk Investigational Site	Kalamazoo	Michigan	United States	49009
79	Novo Nordisk Investigational Site	Olive Branch	Mississippi	United States	38654-3573
80	Novo Nordisk Investigational Site	Florissant	Missouri	United States	63031
81	Novo Nordisk Investigational Site	Jefferson City	Missouri	United States	65109
82	Novo Nordisk Investigational Site	Kansas City	Missouri	United States	64106
83	Novo Nordisk Investigational Site	Henderson	Nevada	United States	89052-2649
84	Novo Nordisk Investigational Site	Las Vegas	Nevada	United States	89148
85	Novo Nordisk Investigational Site	Newington	New Hampshire	United States	03801
86	Novo Nordisk Investigational Site	Morganville	New Jersey	United States	07751
87	Novo Nordisk Investigational Site	Teaneck	New Jersey	United States	07666
88	Novo Nordisk Investigational Site	Albuquerque	New Mexico	United States	87102
89	Novo Nordisk Investigational Site	Albany	New York	United States	12208
90	Novo Nordisk Investigational Site	Jackson Heights	New York	United States	11372
91	Novo Nordisk Investigational Site	New Windsor	New York	United States	12553
92	Novo Nordisk Investigational Site	Northport	New York	United States	11768
93	Novo Nordisk Investigational Site	Smithtown	New York	United States	11787
94	Novo Nordisk Investigational Site	Charlotte	North Carolina	United States	28277
95	Novo Nordisk Investigational Site	Morganton	North Carolina	United States	28655
96	Novo Nordisk Investigational Site	Winston-Salem	North Carolina	United States	27103
97	Novo Nordisk Investigational Site	Delaware	Ohio	United States	43015
98	Novo Nordisk Investigational Site	Franklin	Ohio	United States	45005
99	Novo Nordisk Investigational Site	Toledo	Ohio	United States	43614
100	Novo Nordisk Investigational Site	Oklahoma City	Oklahoma	United States	73103
101	Novo Nordisk Investigational Site	Altoona	Pennsylvania	United States	16602
102	Novo Nordisk Investigational Site	Beaver	Pennsylvania	United States	15009
103	Novo Nordisk Investigational Site	Philadelphia	Pennsylvania	United States	19107
104	Novo Nordisk Investigational Site	Philadelphia	Pennsylvania	United States	19114
105	Novo Nordisk Investigational Site	Scottdale	Pennsylvania	United States	15683
106	Novo Nordisk Investigational Site	Anderson	South Carolina	United States	29621
107	Novo Nordisk Investigational Site	Gaffney	South Carolina	United States	29341
108	Novo Nordisk Investigational Site	Greer	South Carolina	United States	29651
109	Novo Nordisk Investigational Site	Pelzer	South Carolina	United States	29669
110	Novo Nordisk Investigational Site	Spartanburg	South Carolina	United States	29303
111	Novo Nordisk Investigational Site	Rapid City	South Dakota	United States	57701
112	Novo Nordisk Investigational Site	Bristol	Tennessee	United States	37620-7352
113	Novo Nordisk Investigational Site	Bristol	Tennessee	United States	37620
114	Novo Nordisk Investigational Site	Chattanooga	Tennessee	United States	37404
115	Novo Nordisk Investigational Site	Humboldt	Tennessee	United States	38343
116	Novo Nordisk Investigational Site	Jackson	Tennessee	United States	38305
117	Novo Nordisk Investigational Site	Johnson City	Tennessee	United States	37604
118	Novo Nordisk Investigational Site	Kingsport	Tennessee	United States	37660
119	Novo Nordisk Investigational Site	Arlington	Texas	United States	76012-4637
120	Novo Nordisk Investigational Site	Arlington	Texas	United States	76012
121	Novo Nordisk Investigational Site	Austin	Texas	United States	78758
122	Novo Nordisk Investigational Site	Carrollton	Texas	United States	75007
123	Novo Nordisk Investigational Site	Dallas	Texas	United States	75208
124	Novo Nordisk Investigational Site	El Paso	Texas	United States	79912
125	Novo Nordisk Investigational Site	Fort Worth	Texas	United States	76104
126	Novo Nordisk Investigational Site	Houston	Texas	United States	77040
127	Novo Nordisk Investigational Site	Houston	Texas	United States	77043
128	Novo Nordisk Investigational Site	Houston	Texas	United States	77060
129	Novo Nordisk Investigational Site	Houston	Texas	United States	77070
130	Novo Nordisk Investigational Site	Houston	Texas	United States	77072
131	Novo Nordisk Investigational Site	Houston	Texas	United States	77077
132	Novo Nordisk Investigational Site	Humble	Texas	United States	77338
133	Novo Nordisk Investigational Site	Hurst	Texas	United States	76054
134	Novo Nordisk Investigational Site	Marshall	Texas	United States	75670
135	Novo Nordisk Investigational Site	Mesquite	Texas	United States	75149
136	Novo Nordisk Investigational Site	North Richland Hills	Texas	United States	76180
137	Novo Nordisk Investigational Site	Plano	Texas	United States	75075
138	Novo Nordisk Investigational Site	Plano	Texas	United States	75093
139	Novo Nordisk Investigational Site	Richardson	Texas	United States	75080
140	Novo Nordisk Investigational Site	San Antonio	Texas	United States	78215
141	Novo Nordisk Investigational Site	San Antonio	Texas	United States	78224
142	Novo Nordisk Investigational Site	San Antonio	Texas	United States	78228-3419
143	Novo Nordisk Investigational Site	San Antonio	Texas	United States	78229
144	Novo Nordisk Investigational Site	San Antonio	Texas	United States	78240
145	Novo Nordisk Investigational Site	San Antonio	Texas	United States	78258
146	Novo Nordisk Investigational Site	Sealy	Texas	United States	77474
147	Novo Nordisk Investigational Site	Sugar Land	Texas	United States	77478
148	Novo Nordisk Investigational Site	Sugar Land	Texas	United States	77479
149	Novo Nordisk Investigational Site	Victoria	Texas	United States	77901
150	Novo Nordisk Investigational Site	Waco	Texas	United States	76710
151	Novo Nordisk Investigational Site	Draper	Utah	United States	84020
152	Novo Nordisk Investigational Site	Ogden	Utah	United States	84405
153	Novo Nordisk Investigational Site	Salt Lake City	Utah	United States	84107
154	Novo Nordisk Investigational Site	Chesapeake	Virginia	United States	23321
155	Novo Nordisk Investigational Site	Norfolk	Virginia	United States	23510
156	Novo Nordisk Investigational Site	Olympia	Washington	United States	98502
157	Novo Nordisk Investigational Site	Renton	Washington	United States	98057
158	Novo Nordisk Investigational Site	Richland	Washington	United States	99352
159	Novo Nordisk Investigational Site	Spokane	Washington	United States	99202-1334
160	Novo Nordisk Investigational Site	Martinsburg	West Virginia	United States	25401
161	Novo Nordisk Investigational Site	Kenosha	Wisconsin	United States	53144
162	Novo Nordisk Investigational Site	Carolina		Puerto Rico	00983
163	Novo Nordisk Investigational Site	Manati		Puerto Rico	00674
164	Novo Nordisk Investigational Site	Ponce		Puerto Rico	00717
165	Novo Nordisk Investigational Site	San Juan		Puerto Rico	00918
166	Novo Nordisk Investigational Site	San Juan		Puerto Rico	00921

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

• Chaykin L, Bhargava A, de la Rosa R, Wysham CH, Nørgård Troelsen L, Østoft SH, Philis-Tsimikas A. Effect of Insulin Degludec Versus Insulin Glargine U100 on Hypoglycemia in Hispanic Patients With Type 2 Diabetes: Results From the SWITCH 2 Trial. Clin Diabetes. 2019 Jan;37(1):73-81. doi: 10.2337/cd18-0016.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT02030600
• Other Study ID Numbers: NN1250-3998; U1111-1143-7963
• First Posted: Jan 8, 2014
• Last Update Posted: May 10, 2019
• Last Verified: Apr 1, 2019

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

Study Results

Participant Flow

Recruitment Details	The trial was conducted at 152 sites in the United States.

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 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 at the same time of day throughout the trial. Subjects receiving pre-trial once daily basal insulin were to continue on their pre-trial basal insulin dose. For subjects receiving pre-trial twice daily basal insulin, a 20% reduction of the total daily insulin dose was recommended. Doses of IDeg and IGlar were titrated individually. Adjustment of the dose was performed once weekly based on the mean of 3 preceding daily fasting self-measured plasma glucose (SMPG) values on 3 consecutive days (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 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 at the same time of day throughout the trial. Subjects receiving pre-trial once daily basal insulin were to continue on their pre-trial basal insulin dose. For subjects receiving pre-trial twice daily basal insulin, a 20% reduction of the total insulin daily dose was recommended. Doses of IGlar and IDeg were titrated individually. Adjustment of the dose was performed once weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-5.0 mmol/L).
Period Title: Treatment Period 1
STARTED	361	360
Exposed	356	357
COMPLETED	308	315
NOT COMPLETED	53	45
Period Title: Treatment Period 1
STARTED	308	315
COMPLETED	283	297
NOT COMPLETED	25	18

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 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 at the same time of day throughout the trial. Subjects receiving pre-trial once daily basal insulin were to continue on their pre-trial basal insulin dose. For subjects receiving pre-trial twice daily basal insulin, a 20% reduction of the total daily insulin dose was recommended. Doses of IDeg and IGlar were titrated individually. Adjustment of the dose was performed once weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (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 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 at the same time of day throughout the trial. Subjects receiving pre-trial once daily basal insulin were to continue on their pre-trial basal insulin dose. For subjects receiving pre-trial twice daily basal insulin, a 20% reduction of the total insulin daily dose was recommended. Doses of IGlar and IDeg were titrated individually. Adjustment of the dose was performed once weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-5.0 mmol/L).	Total of all reporting groups
Overall Participants	360	360	720
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.5 (10.7)	61.2 (10.3)	61.4 (10.5)
Sex: Female, Male (Count of Participants)
Female	169 46.9%	169 46.9%	338 46.9%
Male	191 53.1%	191 53.1%	382 53.1%
Glycosylated haemoglobin (percentage of glycosylated haemoglobin) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of glycosylated haemoglobin]	7.6 (1.1)	7.6 (1.1)	7.6 (1.1)
Fasting plasma glucose (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	139.2 (53.5)	134.9 (51.6)	137.0 (52.6)

Outcome Measures

1. Primary Outcome

Title	Number of Treatment Emergent Severe or BG 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 <56 mg/dL (3.1 mmol/L), 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.
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 safety analysis set (subjects receiving at least one dose of the investigational product or its comparator). Number of subjects analysed=subjects with available data for the endpoint as per individual trial products. Statistical analysis was performed on full analysis set

Arm/Group Title	Insulin Degludec (IDeg)	Insulin Glargine (IGlar)
Arm/Group Description	Subjects receiving 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 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 at same time of day throughout the trial. Subjects receiving pre-trial once daily basal insulin were to continue on their pre-trial basal insulin dose. For subjects receiving pre-trial twice daily basal insulin, a 20% reduction of the total daily insulin dose was recommended. Dose of IDeg was titrated individually. Adjustment of dose was performed once weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-5.0 mmol/L).	Subjects receiving 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 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 at same time of day throughout the trial. Subjects receiving pre-trial once daily basal insulin were to continue on their pre-trial basal insulin dose. For subjects receiving pre-trial twice daily basal insulin, a 20% reduction of the total daily insulin dose was recommended. Dose of IGlar was titrated individually. Adjustment of dose was performed once weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-5.0 mmol/L).
Measure Participants	632	618
Number [events]	353	496

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Degludec (IDeg), Insulin Glargine (IGlar)
	Comments	Stepwise hierarchical testing procedure was applied for confirmatory endpoints: Step 1: Primary analysis: Number of treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes during the maintenance period
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Poisson
	Comments
Method of Estimation	Estimation Parameter	Treatment ratio
	Estimated Value	0.70
	Confidence Interval	(2-Sided) 95%; 0.61 to 0.80
	Parameter Dispersion	Type: Value:
	Estimation Comments	Superiority was considered confirmed if the 95% confidence interval for the rate ratio (IDeg/IGlar) was entirely below 1.0.

2. Secondary Outcome

Title	Number of Treatment Emergent Severe or BG Confirmed Symptomatic Nocturnal Hypoglycaemic Episode 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 <56 mg/dL (3.1 mmol/L), 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 safety analysis set (subjects receiving at least one dose of the investigational product or its comparator). Number of subjects analysed=subjects with available data for the endpoint as per individual trial products. Statistical analysis was performed on full analysis set

Arm/Group Title	Insulin Degludec (IDeg)	Insulin Glargine (IGlar)
Arm/Group Description	Subjects receiving 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 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 at same time of day throughout the trial. Subjects receiving pre-trial once daily basal insulin were to continue on their pre-trial basal insulin dose. For subjects receiving pre-trial twice daily basal insulin, a 20% reduction of the total daily insulin dose was recommended. Dose of IDeg was titrated individually. Adjustment of dose was performed once weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-5.0 mmol/L).	Subjects receiving 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 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 at same time of day throughout the trial. Subjects receiving pre-trial once daily basal insulin were to continue on their pre-trial basal insulin dose. For subjects receiving pre-trial twice daily basal insulin, a 20% reduction of the total daily insulin dose was recommended. Dose of IGlar was titrated individually. Adjustment of dose was performed once weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-5.0 mmol/L).
Measure Participants	632	618
Number [events]	105	175

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Degludec (IDeg), Insulin Glargine (IGlar)
	Comments	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	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Poisson
	Comments
Method of Estimation	Estimation Parameter	Treatment ratio
	Estimated Value	0.58
	Confidence Interval	(2-Sided) 95%; 0.46 to 0.74
	Parameter Dispersion	Type: Value:
	Estimation Comments	Superiority was considered confirmed if the 95% confidence interval for the rate ratio (IDeg/IGlar) was entirely below 1.0.

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 safety analysis set. Number of subjects analysed=subjects with available data for the endpoint as per individual trial products. Statistical analysis was performed on subjects in full analysis set with exposure in both maintenance periods.

Arm/Group Title	Insulin Degludec (IDeg)	Insulin Glargine (IGlar)
Arm/Group Description	Subjects receiving 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 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 at same time of day throughout the trial. Subjects receiving pre-trial once daily basal insulin were to continue on their pre-trial basal insulin dose. For subjects receiving pre-trial twice daily basal insulin, a 20% reduction of the total daily insulin dose was recommended. Dose of IDeg was titrated individually. Adjustment of dose was performed once weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-5.0 mmol/L).	Subjects receiving 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 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 at same time of day throughout the trial. Subjects receiving pre-trial once daily basal insulin were to continue on their pre-trial basal insulin dose. For subjects receiving pre-trial twice daily basal insulin, a 20% reduction of the total daily insulin dose was recommended. Dose of IGlar was titrated individually. Adjustment of dose was performed once weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-5.0 mmol/L).
Measure Participants	632	618
Number [percentage of subjects]	1.6	2.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Degludec (IDeg), Insulin Glargine (IGlar)
	Comments	Stepwise hierarchical testing procedure: Step 3: Proportion of subjects with one or more severe hypoglycaemic episodes in the maintenance period.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3458
	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

Safety analysis set included all subjects receiving at least one dose of the investigational product or its comparator (Total number of subjects analysed for this endpoint: 713).

Arm/Group Title	Insulin Degludec (IDeg)	Insulin Glargine (IGlar)
Arm/Group Description	Subjects receiving 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 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 at same time of day throughout the trial. Subjects receiving pre-trial once daily basal insulin were to continue on their pre-trial basal insulin dose. For subjects receiving pre-trial twice daily basal insulin, a 20% reduction of the total daily insulin dose was recommended. Dose of IDeg was titrated individually. Adjustment of dose was performed once weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-5.0 mmol/L).	Subjects receiving 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 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 at same time of day throughout the trial. Subjects receiving pre-trial once daily basal insulin were to continue on their pre-trial basal insulin dose. For subjects receiving pre-trial twice daily basal insulin, a 20% reduction of the total daily insulin dose was recommended. Dose of IGlar was titrated individually. Adjustment of dose was performed once weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-5.0 mmol/L).
Measure Participants	671	665
Number [events]	1293	1381

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 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

Full analysis set. Here, 'n' specifies the number of subjects with available data at specified timepoint.

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 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 at the same time of day throughout the trial. Subjects receiving pre-trial once daily basal insulin were to continue on their pre-trial basal insulin dose. For subjects receiving pre-trial twice daily basal insulin, a 20% reduction of the total daily insulin dose was recommended. Doses of IDeg and IGlar were titrated individually. Adjustment of the dose was performed once weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (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 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 at the same time of day throughout the trial. Subjects receiving pre-trial once daily basal insulin were to continue on their pre-trial basal insulin dose. For subjects receiving pre-trial twice daily basal insulin, a 20% reduction of the total insulin daily dose was recommended. Doses of IGlar and IDeg were titrated individually. Adjustment of the dose was performed once weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-5.0 mmol/L).
Measure Participants	360	360
week 32 (n=308, 313)	-0.49 (0.99)	-0.58 (1.02)
week 64 (n=295, 301)	0.03 (0.75)	0.10 (0.83)

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 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 performed using a mixed model for repeated measurement (MMRM) with treatment, sex, antidiabetic therapy at screening, visit and dosing time as fixed effects, and age and baseline HbA1c as covariates.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority of IDeg against IGlar was considered confirmed if the upper bound of the two-sided 95% confidence interval was below or equal to 0.40%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment contrast
	Estimated Value	0.09
	Confidence Interval	(2-Sided) 95%; -0.04 to 0.23
	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 performed using a MMRM with treatment, sex, antidiabetic therapy at screening, visit and dosing time as fixed effects, and age and baseline HbA1c as 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%
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Treatment contrast
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 95%; -0.07 to 0.18
	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, week 64

Outcome Measure Data

Analysis Population Description

Full analysis set. Here, 'n' specifies the number of subjects with available data at specified timepoint.

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 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 at the same time of day throughout the trial. Subjects receiving pre-trial once daily basal insulin were to continue on their pre-trial basal insulin dose. For subjects receiving pre-trial twice daily basal insulin, a 20% reduction of the total daily insulin dose was recommended. Doses of IDeg and IGlar were titrated individually. Adjustment of the dose was performed once weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (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 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 at the same time of day throughout the trial. Subjects receiving pre-trial once daily basal insulin were to continue on their pre-trial basal insulin dose. For subjects receiving pre-trial twice daily basal insulin, a 20% reduction of the total insulin daily dose was recommended. Doses of IGlar and IDeg were titrated individually. Adjustment of the dose was performed once weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-5.0 mmol/L).
Measure Participants	360	360
week 32 (n=307, 311)	107.33 (41.72)	106.96 (39.81)
week 64 (n=293, 302)	114.07 (51.91)	107.55 (51.30)

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 safety analysis set contributed to the evaluation of adverse events. 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.
Arm/Group Title	Insulin Degludec (IDeg)		Insulin Glargine (IGlar)
Arm/Group Description	Subjects receiving 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 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 at same time of day throughout the trial. Subjects receiving pre-trial once daily basal insulin were to continue on their pre-trial basal insulin dose. For subjects receiving pre-trial twice daily basal insulin, a 20% reduction of the total daily insulin dose was recommended. Dose of IDeg was titrated individually. Adjustment of dose was performed once weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-5.0 mmol/L).		Subjects receiving 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 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 at same time of day throughout the trial. Subjects receiving pre-trial once daily basal insulin were to continue on their pre-trial basal insulin dose. For subjects receiving pre-trial twice daily basal insulin, a 20% reduction of the total daily insulin dose was recommended. Dose of IGlar was titrated individually. Adjustment of dose was performed once weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (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	64/671 (9.5%)		65/665 (9.8%)
Blood and lymphatic system disorders
Leukocytosis	0/671 (0%)	0	1/665 (0.2%)	1
Cardiac disorders
Acute coronary syndrome	1/671 (0.1%)	1	0/665 (0%)	0
Acute myocardial infarction	2/671 (0.3%)	2	1/665 (0.2%)	1
Angina pectoris	1/671 (0.1%)	1	4/665 (0.6%)	4
Angina unstable	0/671 (0%)	0	2/665 (0.3%)	2
Atrial fibrillation	0/671 (0%)	0	1/665 (0.2%)	1
Cardiac failure	1/671 (0.1%)	1	0/665 (0%)	0
Cardiac failure congestive	1/671 (0.1%)	1	2/665 (0.3%)	2
Coronary artery disease	2/671 (0.3%)	2	3/665 (0.5%)	3
Coronary artery dissection	1/671 (0.1%)	1	0/665 (0%)	0
Coronary artery occlusion	1/671 (0.1%)	1	0/665 (0%)	0
Intracardiac thrombus	1/671 (0.1%)	1	0/665 (0%)	0
Myocardial infarction	0/671 (0%)	0	1/665 (0.2%)	1
Myocardial ischaemia	0/671 (0%)	0	1/665 (0.2%)	1
Supraventricular tachycardia	0/671 (0%)	0	1/665 (0.2%)	1
Ventricular tachycardia	1/671 (0.1%)	1	0/665 (0%)	0
Eye disorders
Iridocyclitis	1/671 (0.1%)	1	0/665 (0%)	0
Gastrointestinal disorders
Colitis ischaemic	0/671 (0%)	0	1/665 (0.2%)	1
Diarrhoea	0/671 (0%)	0	1/665 (0.2%)	1
Diverticular fistula	0/671 (0%)	0	1/665 (0.2%)	1
Flatulence	1/671 (0.1%)	1	0/665 (0%)	0
Impaired gastric emptying	0/671 (0%)	0	1/665 (0.2%)	1
Inguinal hernia	0/671 (0%)	0	1/665 (0.2%)	1
Intestinal obstruction	1/671 (0.1%)	1	0/665 (0%)	0
Pancreatitis	0/671 (0%)	0	1/665 (0.2%)	1
Small intestinal obstruction	0/671 (0%)	0	1/665 (0.2%)	1
Vomiting	0/671 (0%)	0	1/665 (0.2%)	1
General disorders
Chest discomfort	0/671 (0%)	0	1/665 (0.2%)	1
Chest pain	1/671 (0.1%)	1	0/665 (0%)	0
Lead dislodgement	1/671 (0.1%)	1	0/665 (0%)	0
Non-cardiac chest pain	3/671 (0.4%)	3	3/665 (0.5%)	3
Hepatobiliary disorders
Cholelithiasis	0/671 (0%)	0	1/665 (0.2%)	1
Hepatic cyst	0/671 (0%)	0	1/665 (0.2%)	1
Jaundice cholestatic	0/671 (0%)	0	1/665 (0.2%)	1
Infections and infestations
Appendicitis	1/671 (0.1%)	1	0/665 (0%)	0
Bronchitis	0/671 (0%)	0	1/665 (0.2%)	1
Bronchopulmonary aspergillosis	0/671 (0%)	0	1/665 (0.2%)	1
Cellulitis	1/671 (0.1%)	1	0/665 (0%)	0
Cellulitis staphylococcal	1/671 (0.1%)	1	0/665 (0%)	0
Cystitis	0/671 (0%)	0	1/665 (0.2%)	1
Diverticulitis	2/671 (0.3%)	2	0/665 (0%)	0
Gastroenteritis	1/671 (0.1%)	1	1/665 (0.2%)	1
Influenza	0/671 (0%)	0	1/665 (0.2%)	1
Mastoiditis	1/671 (0.1%)	1	0/665 (0%)	0
Ophthalmic herpes zoster	1/671 (0.1%)	1	0/665 (0%)	0
Osteomyelitis	1/671 (0.1%)	1	0/665 (0%)	0
Otitis externa	1/671 (0.1%)	1	0/665 (0%)	0
Pneumonia	0/671 (0%)	0	1/665 (0.2%)	1
Postoperative wound infection	0/671 (0%)	0	1/665 (0.2%)	1
Salmonella sepsis	0/671 (0%)	0	1/665 (0.2%)	1
Sepsis	1/671 (0.1%)	1	4/665 (0.6%)	4
Staphylococcal sepsis	0/671 (0%)	0	1/665 (0.2%)	1
Urinary tract infection	0/671 (0%)	0	1/665 (0.2%)	1
Injury, poisoning and procedural complications
Ankle fracture	1/671 (0.1%)	1	0/665 (0%)	0
Confusion postoperative	0/671 (0%)	0	1/665 (0.2%)	1
Drug dispensing error	1/671 (0.1%)	1	0/665 (0%)	0
Fall	1/671 (0.1%)	1	1/665 (0.2%)	1
Hip fracture	1/671 (0.1%)	1	0/665 (0%)	0
Lumbar vertebral fracture	0/671 (0%)	0	1/665 (0.2%)	1
Medication error	0/671 (0%)	0	1/665 (0.2%)	1
Post lumbar puncture syndrome	1/671 (0.1%)	2	0/665 (0%)	0
Road traffic accident	2/671 (0.3%)	2	1/665 (0.2%)	1
Sternal fracture	0/671 (0%)	0	1/665 (0.2%)	1
Toxicity to various agents	1/671 (0.1%)	1	0/665 (0%)	0
Wrist fracture	1/671 (0.1%)	1	0/665 (0%)	0
Investigations
Computerised tomogram thorax abnormal	1/671 (0.1%)	1	0/665 (0%)	0
Metabolism and nutrition disorders
Dehydration	2/671 (0.3%)	2	1/665 (0.2%)	1
Electrolyte imbalance	0/671 (0%)	0	1/665 (0.2%)	1
Hypoglycaemia	2/671 (0.3%)	2	9/665 (1.4%)	9
Hyponatraemia	0/671 (0%)	0	1/665 (0.2%)	1
Musculoskeletal and connective tissue disorders
Arthritis	2/671 (0.3%)	2	0/665 (0%)	0
Back pain	1/671 (0.1%)	1	0/665 (0%)	0
Cervical spinal stenosis	0/671 (0%)	0	1/665 (0.2%)	1
Fibromyalgia	0/671 (0%)	0	1/665 (0.2%)	1
Intervertebral disc protrusion	0/671 (0%)	0	1/665 (0.2%)	1
Osteoarthritis	2/671 (0.3%)	2	1/665 (0.2%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Brain neoplasm	0/671 (0%)	0	1/665 (0.2%)	1
Breast cancer	0/671 (0%)	0	1/665 (0.2%)	1
Breast cancer stage I	1/671 (0.1%)	1	0/665 (0%)	0
Colon cancer metastatic	1/671 (0.1%)	1	0/665 (0%)	0
Lung adenocarcinoma	1/671 (0.1%)	1	0/665 (0%)	0
Metastases to bone	0/671 (0%)	0	1/665 (0.2%)	1
Non-Hodgkin's lymphoma	0/671 (0%)	0	1/665 (0.2%)	1
Pancreatic carcinoma	2/671 (0.3%)	2	0/665 (0%)	0
Pituitary tumour benign	1/671 (0.1%)	1	0/665 (0%)	0
Prostate cancer	1/671 (0.1%)	1	0/665 (0%)	0
Squamous cell carcinoma	0/671 (0%)	0	1/665 (0.2%)	1
Nervous system disorders
Aphasia	1/671 (0.1%)	1	0/665 (0%)	0
Carpal tunnel syndrome	0/671 (0%)	0	1/665 (0.2%)	1
Cerebrovascular accident	1/671 (0.1%)	1	1/665 (0.2%)	1
Cervical radiculopathy	0/671 (0%)	0	1/665 (0.2%)	1
Hypoglycaemic unconsciousness	0/671 (0%)	0	1/665 (0.2%)	1
Ischaemic stroke	1/671 (0.1%)	1	0/665 (0%)	0
Lacunar stroke	1/671 (0.1%)	1	0/665 (0%)	0
Syncope	2/671 (0.3%)	2	1/665 (0.2%)	1
Thalamic infarction	1/671 (0.1%)	1	0/665 (0%)	0
Toxic encephalopathy	0/671 (0%)	0	1/665 (0.2%)	1
Transient ischaemic attack	0/671 (0%)	0	2/665 (0.3%)	2
Vertebral artery thrombosis	1/671 (0.1%)	1	0/665 (0%)	0
Psychiatric disorders
Abnormal behaviour	1/671 (0.1%)	1	0/665 (0%)	0
Anxiety	1/671 (0.1%)	1	0/665 (0%)	0
Bipolar I disorder	0/671 (0%)	0	1/665 (0.2%)	1
Confusional state	0/671 (0%)	0	1/665 (0.2%)	1
Mental status changes	0/671 (0%)	0	1/665 (0.2%)	1
Panic attack	0/671 (0%)	0	1/665 (0.2%)	1
Renal and urinary disorders
Calculus bladder	1/671 (0.1%)	1	0/665 (0%)	0
Nephrolithiasis	1/671 (0.1%)	1	1/665 (0.2%)	1
Renal cyst	0/671 (0%)	0	2/665 (0.3%)	2
Renal failure	1/671 (0.1%)	1	0/665 (0%)	0
Reproductive system and breast disorders
Ovarian mass	1/671 (0.1%)	1	0/665 (0%)	0
Respiratory, thoracic and mediastinal disorders
Asthma	1/671 (0.1%)	1	2/665 (0.3%)	2
Chronic obstructive pulmonary disease	0/671 (0%)	0	1/665 (0.2%)	1
Dyspnoea	1/671 (0.1%)	2	0/665 (0%)	0
Pleural effusion	1/671 (0.1%)	1	0/665 (0%)	0
Pulmonary oedema	1/671 (0.1%)	1	0/665 (0%)	0
Surgical and medical procedures
Carpal tunnel decompression	0/671 (0%)	0	1/665 (0.2%)	1
Mitral valve repair	0/671 (0%)	0	1/665 (0.2%)	1
Prostatic operation	1/671 (0.1%)	1	0/665 (0%)	0
Surgery	0/671 (0%)	0	1/665 (0.2%)	1
Vascular disorders
Aortic aneurysm	1/671 (0.1%)	1	0/665 (0%)	0
Aortic stenosis	0/671 (0%)	0	1/665 (0.2%)	1
Deep vein thrombosis	0/671 (0%)	0	1/665 (0.2%)	1
Peripheral vascular disorder	1/671 (0.1%)	1	0/665 (0%)	0
Other (Not Including Serious) Adverse Events
	Insulin Degludec (IDeg)		Insulin Glargine (IGlar)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	93/671 (13.9%)		77/665 (11.6%)
Infections and infestations
Nasopharyngitis	50/671 (7.5%)	59	41/665 (6.2%)	49
Upper respiratory tract infection	44/671 (6.6%)	53	37/665 (5.6%)	44

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 manuscripts for publication will be prepared collaboratively between Investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for less than 60 days to protect intellectual property.