A Research Study to Compare the Effect of Insulin Degludec and Insulin Glargine on Blood Sugar Levels in People With Type 2 Diabetes - the SWITCH PRO Study

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03687827
• Collaborator: (none)
• Enrollment: 498
• Locations: 67
• Arms: 2
• Actual Duration (Months): 14.8
• Patients Per Site: 7.4
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This study compares the effect on blood sugar levels of two medicines: insulin degludec and insulin glargine in people with type 2 diabetes. Participants will be treated with insulin degludec and insulin glargine during two different periods. Which treatment participants get first is decided by chance. Both medicines are approved for use in humans and available on the market. They can already be prescribed by participants' doctors. Participants will get pre-filled insulin pens to inject these insulins with. The study will last for about 41 weeks. Participants will visit the clinic 13 times and have 27 phone calls with the study doctor or study staff. At 12 of the clinic visits they will take blood samples. In order to evaluate the changes in participants' blood sugar level over time, participants will be asked to wear a small (35 millimetres (mm) x 5 mm) sensor on the back of participants' upper arm 3 times during the study. Each time participants must wear the sensor for 2 weeks. This sensor is called FreeStyle Libre Pro®. It has a very small tip which is 0.4 mm thick and is inserted 5 mm under participants' skin. Please note that participants will not be able to see the sensor readings while wearing it. The study doctor will show participants the readings when participants return to the clinic. Participants will be asked to fill in a diary in between visits. Participants will have contact with the study doctor or study staff each week. This is to adjust the dose of participants' study medicines and to ensure that participants are well. Women cannot take part if pregnant, breast-feeding or plan to become pregnant during the study period.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	Drug: Insulin degludec; Drug: Insulin glargine	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 498 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomised, Cross-over, Open-label, Multi-centre Trial Comparing the Effect of Insulin Degludec and Insulin Glargine 100U/mL, With or Without OADs in Subjects With Type 2 Diabetes Using Flash Glucose Monitoring
• Actual Study Start Date: Oct 2, 2018
• Actual Primary Completion Date: Dec 20, 2019
• Actual Study Completion Date: Dec 27, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Insulin degludec Participants will receive insulin degludec in period 1 and 2 in a cross-over manner.	Drug: Insulin degludec; Participants will receive insulin degludec U100 subcutaneous (s.c.) injection once daily for 36 weeks. Doses will be adjusted according to the fasting self-measured plasma glucose (SMPG) values. Participants earlier treated with one or more allowed oral antidiabetic drug(s) (OAD(s)), should continue their pre-trial OAD(s) treatment throughout the trial.; Other Names: Tresiba®
Active Comparator: Insulin glargine Participants will receive insulin glargine in period 1 and 2 in a cross-over manner.	Drug: Insulin glargine; Participants will receive insulin glargine U100 s.c. injection once daily for 36 weeks. Doses will be adjusted according to the fasting SMPG values. Participants earlier treated with one or more allowed OAD(s), should continue their pre-trial OAD(s) treatment throughout the trial.; Other Names: Lantus®

Outcome Measures

Primary Outcome Measures

1. Percentage of Time Spent in Glycaemic Target Range 70-180 mg/dL (3.9-10.0 mmol/L) Both Inclusive, Using Flash Glucose Monitoring (FGM) [During the 2-week maintenance period: weeks 16-17 (period-1) and weeks 34-35 (period-2)]

   The percentage of time spent in glycaemic target range was calculated as the number of recorded measurements in glycaemic target range (70-180 milligrams per deciliter [mg/dL] (3.9-10.0 millimoles per litre [mmol/L]), both inclusive) divided by the total number of recorded measurements. The endpoint is based on data recorded by FGM system. It was required that at least 70% of the planned FGM measurements during weeks 16-17 and weeks 34-35 were available for endpoint data to be included in the analysis.

Secondary Outcome Measures

1. Time Spent in Tight Glycaemic Target Range 70-140 mg/dL (3.9-7.8 mmol/L) Both Inclusive, Using Flash Glucose Monitoring [During the 2-week maintenance period: weeks 16-17 (period-1) and weeks 34-35 (period-2).]

   The percentage of time spent in tight glycaemic target range 70-140 mg/dL (3.9-7.8 mmol/L) both inclusive, during the 2-week maintenance periods using FGM (visit 9-21 (week 16-17) and visit 37-39 (week 34-35)).

2. Time Spent in Nocturnal Glycaemic Target Range 70-140 mg/dL (3.9-7.8 mmol/L) Both Inclusive, in the Nocturnal Period (00:01 am - 05:59 am Both Inclusive) Using Flash Glucose Monitoring [During the 2-week maintenance period: weeks 16-17 (period-1) and weeks 34-35 (period-2).]

   Percentage of time spent in nocturnal glycaemic target range 70-140 mg/dL (3.9-7.8 mmol/L) both inclusive, in the nocturnal period (00:01 am - 05:59 am both inclusive) during the 2-week maintenance periods using FGM (visit 19-21 (week 16-17) and visit 37-39 (week 34-35)).

3. Level of Glycated Haemoglobin (HbA1c) - Percentage [After the 2-week maintenance period: weeks 16-17 (period-1) and weeks 34-35 (period-2).]

   Level of HbA1c after two weeks of maintenance periods (Visit 19-21 (week 16-17) and Visit 37-39 (week 34-35)).

4. Level of Glycated Haemoglobin (HbA1c) - mmol/Mol [After the 2-week maintenance period: weeks 16-17 (period-1) and weeks 34-35 (period-2).]

   Level of HbA1c after two weeks of maintenance periods (Visit 19-21 (week 16-17) and Visit 37-39 (week 34-35)).

5. Mean Glucose Levels Using Flash Glucose Monitoring (FGM) [During the 2-week maintenance period: weeks 16-17 (period-1) and weeks 34-35 (period-2).]

   Mean glucose levels (mmol/L) during the 2-week maintenance periods using FGM (visit 19-21 (week 16-17) and visit 37-39 (week 34-35)).

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 greater than or equal to 18 years at the time of signing informed consent

• Diagnosed with type 2 diabetes mellitus greater than or equal to 180 days prior to the day of screening

• Subjects fulfilling at least one of the below criteria:

• Experienced at least one severe hypoglycaemic episode within the last year prior to screening (according to the American Diabetes Association definition, January 2018)*

• Moderate renal impairment defined as estimated glomerular filtration rate value of 30-59 mL/min/1.73 m^2 as defined by Kidney Disease Improving Global Outcomes 2012 at screening

• Known hypoglycaemic unawareness as indicated by the investigator according to Clarke's questionnaire question 8 at screening

• Treated with insulin for more than 5 years

• Episode of hypoglycaemia (defined a glucose alert value of 70 mg/dL (3.9 mmol/L) or less, i.e., Level 1) within the last 12 weeks prior to screening visit

• Treated with any basal insulin greater than or equal to 90 days prior to the day of screening with or without any of the following anti-diabetic drugs:

• Metformin

• Dipeptidyl peptidase-4 inhibitor

• Sodium-glucose co-transporter 2 inhibitor

• Alpha-glucosidase-inhibitors (acarbose)

• Thiazolidinediones

• Marketed oral combination products only including the products listed above

• HbA1c less than or equal to 9.5% (80 mmol/mol) at screening confirmed by central laboratory analysis

• Body mass index less than or equal to 45 kg/m^2 *Hypoglycaemia associated with severe cognitive impairment requiring external assistance for recovery

Exclusion Criteria:

• Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within the past 90 days prior to the day of screening. However, intermittent bolus insulin treatment for periods of no longer than 14 days are permitted prior to the day of screening

• Anticipated initiation or change in concomitant medications known to affect weight or glucose metabolism (e.g., treatment with orlistat, thyroid hormones, or corticosteroids)

• Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a pharmacologically pupil-dilated fundus examination performed by an ophthalmologist or another suitably qualified health care provider within the past 90 days prior to screening or in the period between screening and run-in

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Chandler	Arizona	United States	85224
2	Novo Nordisk Investigational Site	Tucson	Arizona	United States	85741
3	Novo Nordisk Investigational Site	Fresno	California	United States	93720
4	Novo Nordisk Investigational Site	Lancaster	California	United States	93534
5	Novo Nordisk Investigational Site	Northridge	California	United States	91325
6	Novo Nordisk Investigational Site	Poway	California	United States	92064
7	Novo Nordisk Investigational Site	Van Nuys	California	United States	91405
8	Novo Nordisk Investigational Site	Hamden	Connecticut	United States	06517
9	Novo Nordisk Investigational Site	Bradenton	Florida	United States	34201
10	Novo Nordisk Investigational Site	Cooper City	Florida	United States	33024
11	Novo Nordisk Investigational Site	Hollywood	Florida	United States	33024
12	Novo Nordisk Investigational Site	New Port Richey	Florida	United States	34652
13	Novo Nordisk Investigational Site	Orlando	Florida	United States	32825
14	Novo Nordisk Investigational Site	Pembroke Pines	Florida	United States	33027
15	Novo Nordisk Investigational Site	Skokie	Illinois	United States	60077
16	Novo Nordisk Investigational Site	Topeka	Kansas	United States	66606
17	Novo Nordisk Investigational Site	Lexington	Kentucky	United States	40503
18	Novo Nordisk Investigational Site	Louisville	Kentucky	United States	40213
19	Novo Nordisk Investigational Site	Boston	Massachusetts	United States	02115-5804
20	Novo Nordisk Investigational Site	Boston	Massachusetts	United States	02118
21	Novo Nordisk Investigational Site	Kalispell	Montana	United States	59901
22	Novo Nordisk Investigational Site	New Windsor	New York	United States	12553
23	Novo Nordisk Investigational Site	Greenville	North Carolina	United States	27834
24	Novo Nordisk Investigational Site	Statesville	North Carolina	United States	28625
25	Novo Nordisk Investigational Site	Cincinnati	Ohio	United States	45245
26	Novo Nordisk Investigational Site	Toledo	Ohio	United States	43614
27	Novo Nordisk Investigational Site	Pelzer	South Carolina	United States	29669
28	Novo Nordisk Investigational Site	Dakota Dunes	South Dakota	United States	57049
29	Novo Nordisk Investigational Site	Nashville	Tennessee	United States	37203
30	Novo Nordisk Investigational Site	Amarillo	Texas	United States	79106
31	Novo Nordisk Investigational Site	Kerrville	Texas	United States	78028
32	Novo Nordisk Investigational Site	San Antonio	Texas	United States	78215
33	Novo Nordisk Investigational Site	San Antonio	Texas	United States	78224
34	Novo Nordisk Investigational Site	San Antonio	Texas	United States	78228-6205
35	Novo Nordisk Investigational Site	Calgary	Alberta	Canada	T2H 2G4
36	Novo Nordisk Investigational Site	Victoria	British Columbia	Canada	V8V 4A1
37	Novo Nordisk Investigational Site	Concord	Ontario	Canada	L4K 4M2
38	Novo Nordisk Investigational Site	Etobicoke	Ontario	Canada	M9R 4E1
39	Novo Nordisk Investigational Site	London	Ontario	Canada	N5W 6A2
40	Novo Nordisk Investigational Site	Markham	Ontario	Canada	L3P 7P2
41	Novo Nordisk Investigational Site	Oakville	Ontario	Canada	L6M 1M1
42	Novo Nordisk Investigational Site	Toronto	Ontario	Canada	M4G 3E8
43	Novo Nordisk Investigational Site	Toronto	Ontario	Canada	M6G 1M2
44	Novo Nordisk Investigational Site	Montreal	Quebec	Canada	H4A 2C6
45	Novo Nordisk Investigational Site	Bialystok		Poland	15-351
46	Novo Nordisk Investigational Site	Bialystok		Poland	15-404
47	Novo Nordisk Investigational Site	Gdansk		Poland	80-858
48	Novo Nordisk Investigational Site	Lublin		Poland	20-538
49	Novo Nordisk Investigational Site	Warsaw		Poland	00-465
50	Novo Nordisk Investigational Site	Ponce		Puerto Rico	00716
51	Novo Nordisk Investigational Site	Bratislava		Slovakia	831 01
52	Novo Nordisk Investigational Site	Bratislava		Slovakia	851 01
53	Novo Nordisk Investigational Site	Bytca		Slovakia	014 01
54	Novo Nordisk Investigational Site	Levice		Slovakia	93401
55	Novo Nordisk Investigational Site	Malacky		Slovakia	901 01
56	Novo Nordisk Investigational Site	Nove Mesto nad Vahom		Slovakia	915 01
57	Novo Nordisk Investigational Site	Nove Zamky		Slovakia	940 59
58	Novo Nordisk Investigational Site	Trebisov		Slovakia	07501
59	Novo Nordisk Investigational Site	Trnava		Slovakia	91701
60	Novo Nordisk Investigational Site	Zilina		Slovakia	010 01
61	Novo Nordisk Investigational Site	Port Elizabeth	Eastern Cape	South Africa	6045
62	Novo Nordisk Investigational Site	Bloemfontein	Free State	South Africa	9301
63	Novo Nordisk Investigational Site	Johannesburg	Gauteng	South Africa	1827
64	Novo Nordisk Investigational Site	Johannesburg	Gauteng	South Africa	1829
65	Novo Nordisk Investigational Site	Lenasia	Gauteng	South Africa	1827
66	Novo Nordisk Investigational Site	Pretoria	Gauteng	South Africa	0044
67	Novo Nordisk Investigational Site	Cape Town	Western Cape	South Africa	7130

Sponsors and Collaborators

• Novo Nordisk A/S

Investigators

• Study Director: Clinical Reporting Anchor and Disclosure (1452), Novo Nordisk A/S

Study Documents (Full-Text)

• Study Protocol - May 4, 2020
• Statistical Analysis Plan - May 4, 2020

More Information

Publications

None provided.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT03687827
• Other Study ID Numbers: NN1250-4419; U1111-1203-0580; 2017-004047-20
• First Posted: Sep 27, 2018
• Last Update Posted: Jan 12, 2021
• Last Verified: Dec 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• 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 in 5 countries as follows: Canada: 10 sites, Poland: 5 sites, Slovakia: 10 sites, South Africa: 7 sites, United States of America: 34 sites
Pre-assignment Detail	This was a cross-over trial. The trial included a 2-week run-in period (which was after the screening visit) for eligibility assessment in regard to adherence to FGM requirements. The participants were randomized into one of two treatment sequences.

Arm/Group Title	Sequence A: Insulin Degludec 100U/mL Then Insulin Glargine 100U/mL	Sequence B: Insulin Glargine 100U/mL Then Insulin Degludec 100U/mL
Arm/Group Description	Participants were to receive a subcutaneous (s.c.) injection of Insulin degludec 100U/mL (Units per milliliter) once daily (in treatment period 1), followed by a s.c. injection of Insulin glargine 100U/mL once daily (in treatment period 2) with or without oral anti-diabetic drugs using flash glucose monitoring. Each treatment period consisted of a 16-week titration period followed by a 2-week maintenance period.	Participants were to receive a subcutaneous (s.c.) injection of Insulin glargine 100U/mL once daily (in treatment period 1), followed by a s.c. injection of Insulin degludec 100U/mL once daily (in treatment period 2) with or without oral anti-diabetic drugs using flash glucose monitoring. Each treatment period consisted of a 16-week titration period followed by a 2-week maintenance period.
Period Title: Treatment Period 1
STARTED	249	249
Full Analysis Set (FAS)	249	249
Safety Analysis Set (SAS)	249	249
Per Protocol Set	219	229
COMPLETED	235	241
NOT COMPLETED	14	8
Period Title: Treatment Period 1
STARTED	235	241
COMPLETED	230	238
NOT COMPLETED	5	3

Baseline Characteristics

Arm/Group Title	Overall Study
Arm/Group Description	Participants were to receive subcutaneous (s.c.) injection of Insulin degludec 100U/mL once daily followed by a s.c. injection of Insulin glargine 100U/mL once daily in 2 treatment periods with or without oral anti-diabetic drugs using flash glucose monitoring. Each treatment period consisted of a 16-week titration period followed by a 2-week maintenance period.
Overall Participants	498
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	62.8 (9.8)
Sex: Female, Male (Count of Participants)
Female	259 52%
Male	239 48%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	100 20.1%
Not Hispanic or Latino	398 79.9%
Unknown or Not Reported	0 0%
Race/Ethnicity, Customized (Number) [Number]
American Indian or Alaska Native	2 0.4%
Asian	23 4.6%
Black or African American	39 7.8%
White	415 83.3%
Other	19 3.8%

Outcome Measures

1. Primary Outcome

Title	Percentage of Time Spent in Glycaemic Target Range 70-180 mg/dL (3.9-10.0 mmol/L) Both Inclusive, Using Flash Glucose Monitoring (FGM)
Description	The percentage of time spent in glycaemic target range was calculated as the number of recorded measurements in glycaemic target range (70-180 milligrams per deciliter [mg/dL] (3.9-10.0 millimoles per litre [mmol/L]), both inclusive) divided by the total number of recorded measurements. The endpoint is based on data recorded by FGM system. It was required that at least 70% of the planned FGM measurements during weeks 16-17 and weeks 34-35 were available for endpoint data to be included in the analysis.
Time Frame	During the 2-week maintenance period: weeks 16-17 (period-1) and weeks 34-35 (period-2)

Outcome Measure Data

Analysis Population Description

Per protocol (PP) analysis set - The PP analysis set consisted of subjects that stayed on assigned treatment until and completed FGM assessment at visits 21 and 39 respectively. Complete FGM assessment was specified as subjects having at least 70% of 2 weeks FGM measurements per maintenance period (2 * 960 measurements).

Arm/Group Title	Insulin Degludec 100U/mL	Insulin Glargine 100U/mL
Arm/Group Description	Participants were to receive a subcutaneous (s.c.) injection of insulin degludec 100U/mL, once daily, in any of the treatment period, with or without oral anti-diabetic drugs using flash glucose monitoring. Each treatment period consisted of a 16-week titration period followed by a 2-week maintenance period.	Participants were to receive a subcutaneous (s.c.) injection of insulin glargine 100U/mL, once daily, in any of the treatment period, with or without oral anti-diabetic drugs using flash glucose monitoring. Each treatment period consisted of a 16-week titration period followed by a 2-week maintenance period.
Measure Participants	448	448
Least Squares Mean (Standard Error) [Percentage of Time]	72.11 (0.74)	70.68 (0.74)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Degludec 100U/mL, Insulin Glargine 100U/mL
	Comments
	Type of Statistical Test	Superiority
	Comments	Superiority is confirmed if non-inferiority is confirmed and the lower limit of the two-sided 95% confidence interval is entirely above zero.
Statistical Test of Hypothesis	p-Value	0.0321
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Estimated treatment difference
	Estimated Value	1.43
	Confidence Interval	(2-Sided) 95%; 0.12 to 2.74
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Insulin Degludec 100U/mL, Insulin Glargine 100U/mL
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	A non-inferiority margin of -0.83% has been applied, corresponding to 0.2 hours/24 hours
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimated treatment difference
	Estimated Value	1.43
	Confidence Interval	(2-Sided) 95%; 0.12 to 2.74
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Time Spent in Tight Glycaemic Target Range 70-140 mg/dL (3.9-7.8 mmol/L) Both Inclusive, Using Flash Glucose Monitoring
Description	The percentage of time spent in tight glycaemic target range 70-140 mg/dL (3.9-7.8 mmol/L) both inclusive, during the 2-week maintenance periods using FGM (visit 9-21 (week 16-17) and visit 37-39 (week 34-35)).
Time Frame	During the 2-week maintenance period: weeks 16-17 (period-1) and weeks 34-35 (period-2).

Outcome Measure Data

Analysis Population Description

Per protocol (PP) analysis set - The PP analysis set consisted of subjects that stayed on assigned treatment until and completed FGM assessment at visits 21 and 39 respectively.

Arm/Group Title	Insulin Degludec 100U/mL	Insulin Glargine 100U/mL
Arm/Group Description	Participants were to receive a subcutaneous (s.c.) injection of insulin degludec 100U/mL, once daily, in any of the treatment period, with or without oral anti-diabetic drugs using flash glucose monitoring. Each treatment period consisted of a 16-week titration period followed by a 2-week maintenance period.	Participants were to receive a subcutaneous (s.c.) injection of insulin glargine 100U/mL, once daily, in any of the treatment period, with or without oral anti-diabetic drugs using flash glucose monitoring. Each treatment period consisted of a 16-week titration period followed by a 2-week maintenance period.
Measure Participants	448	448
Least Squares Mean (Standard Error) [Percentage of Time]	52.97 (0.82)	51.45 (0.82)

3. Secondary Outcome

Title	Time Spent in Nocturnal Glycaemic Target Range 70-140 mg/dL (3.9-7.8 mmol/L) Both Inclusive, in the Nocturnal Period (00:01 am - 05:59 am Both Inclusive) Using Flash Glucose Monitoring
Description	Percentage of time spent in nocturnal glycaemic target range 70-140 mg/dL (3.9-7.8 mmol/L) both inclusive, in the nocturnal period (00:01 am - 05:59 am both inclusive) during the 2-week maintenance periods using FGM (visit 19-21 (week 16-17) and visit 37-39 (week 34-35)).
Time Frame	During the 2-week maintenance period: weeks 16-17 (period-1) and weeks 34-35 (period-2).

Outcome Measure Data

Analysis Population Description

Per protocol (PP) analysis set - The PP analysis set consisted of subjects that stayed on assigned treatment until and completed FGM assessment at visits 21 and 39 respectively.

Arm/Group Title	Insulin Degludec 100U/mL	Insulin Glargine 100U/mL
Arm/Group Description	Participants were to receive a subcutaneous (s.c.) injection of insulin degludec 100U/mL, once daily, in any of the treatment period, with or without oral anti-diabetic drugs using flash glucose monitoring. Each treatment period consisted of a 16-week titration period followed by a 2-week maintenance period.	Participants were to receive a subcutaneous (s.c.) injection of insulin glargine 100U/mL, once daily, in any of the treatment period, with or without oral anti-diabetic drugs using flash glucose monitoring. Each treatment period consisted of a 16-week titration period followed by a 2-week maintenance period.
Measure Participants	448	448
Least Squares Mean (Standard Error) [Percentage of Time]	15.15 (0.26)	14.91 (0.26)

4. Secondary Outcome

Title	Level of Glycated Haemoglobin (HbA1c) - Percentage
Description	Level of HbA1c after two weeks of maintenance periods (Visit 19-21 (week 16-17) and Visit 37-39 (week 34-35)).
Time Frame	After the 2-week maintenance period: weeks 16-17 (period-1) and weeks 34-35 (period-2).

Outcome Measure Data

Analysis Population Description

Per protocol (PP) analysis set - The PP analysis set consisted of subjects that stayed on assigned treatment until and completed FGM assessment at visits 21 and 39 respectively.

Arm/Group Title	Insulin Degludec 100U/mL	Insulin Glargine 100U/mL
Arm/Group Description	Participants were to receive a subcutaneous (s.c.) injection of insulin degludec 100U/mL, once daily, in any of the treatment period, with or without oral anti-diabetic drugs using flash glucose monitoring. Each treatment period consisted of a 16-week titration period followed by a 2-week maintenance period.	Participants were to receive a subcutaneous (s.c.) injection of insulin glargine 100U/mL, once daily, in any of the treatment period, with or without oral anti-diabetic drugs using flash glucose monitoring. Each treatment period consisted of a 16-week titration period followed by a 2-week maintenance period.
Measure Participants	448	448
Least Squares Mean (Standard Error) [Percentage of glycated haemoglobin]	7.10 (0.04)	7.16 (0.04)

5. Secondary Outcome

Title	Level of Glycated Haemoglobin (HbA1c) - mmol/Mol
Description	Level of HbA1c after two weeks of maintenance periods (Visit 19-21 (week 16-17) and Visit 37-39 (week 34-35)).
Time Frame	After the 2-week maintenance period: weeks 16-17 (period-1) and weeks 34-35 (period-2).

Outcome Measure Data

Analysis Population Description

Per protocol (PP) analysis set - The PP analysis set consisted of subjects that stayed on assigned treatment until and completed FGM assessment at visits 21 and 39 respectively.

Arm/Group Title	Insulin Degludec 100U/mL	Insulin Glargine 100U/mL
Arm/Group Description	Participants were to receive a subcutaneous (s.c.) injection of insulin degludec 100U/mL, once daily, in any of the treatment period, with or without oral anti-diabetic drugs using flash glucose monitoring. Each treatment period consisted of a 16-week titration period followed by a 2-week maintenance period.	Participants were to receive a subcutaneous (s.c.) injection of insulin glargine 100U/mL, once daily, in any of the treatment period, with or without oral anti-diabetic drugs using flash glucose monitoring. Each treatment period consisted of a 16-week titration period followed by a 2-week maintenance period.
Measure Participants	448	448
Least Squares Mean (Standard Error) [millimoles per mole (mmol/mol)]	54.10 (0.42)	54.78 (0.42)

6. Secondary Outcome

Title	Mean Glucose Levels Using Flash Glucose Monitoring (FGM)
Description	Mean glucose levels (mmol/L) during the 2-week maintenance periods using FGM (visit 19-21 (week 16-17) and visit 37-39 (week 34-35)).
Time Frame	During the 2-week maintenance period: weeks 16-17 (period-1) and weeks 34-35 (period-2).

Outcome Measure Data

Analysis Population Description

Per protocol (PP) analysis set - The PP analysis set consisted of subjects that stayed on assigned treatment until and completed FGM assessment at visits 21 and 39 respectively.

Arm/Group Title	Insulin Degludec 100U/mL	Insulin Glargine 100U/mL
Arm/Group Description	Participants were to receive a subcutaneous (s.c.) injection of insulin degludec 100U/mL, once daily, in any of the treatment period, with or without oral anti-diabetic drugs using flash glucose monitoring. Each treatment period consisted of a 16-week titration period followed by a 2-week maintenance period.	Participants were to receive a subcutaneous (s.c.) injection of insulin glargine 100U/mL, once daily, in any of the treatment period, with or without oral anti-diabetic drugs using flash glucose monitoring. Each treatment period consisted of a 16-week titration period followed by a 2-week maintenance period.
Measure Participants	448	448
Least Squares Mean (Standard Error) [mmol/L]	7.57 (0.08)	7.61 (0.08)

Adverse Events

Time Frame	From the randomization (week 0) up to end of treatment (week 36) and follow up (week 37).
Adverse Event Reporting Description	Safety Analysis Set was defined as all participants that were randomized and treated with at least one dose of trial drug after randomization.
Arm/Group Title	Insulin Degludec 100U/mL		Insulin Glargine 100U/mL
Arm/Group Description	Participants were to receive a subcutaneous (s.c.) injection of insulin degludec 100U/mL, once daily, in any of the treatment period, with or without oral anti-diabetic drugs using flash glucose monitoring. Each treatment period consisted of a 16-week titration period followed by a 2-week maintenance period.		Participants were to receive a subcutaneous (s.c.) injection of insulin glargine 100U/mL, once daily, in any of the treatment period, with or without oral anti-diabetic drugs using flash glucose monitoring. Each treatment period consisted of a 16-week titration period followed by a 2-week maintenance period.
All Cause Mortality
	Insulin Degludec 100U/mL		Insulin Glargine 100U/mL
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/490 (0%)		1/484 (0.2%)
Serious Adverse Events
	Insulin Degludec 100U/mL		Insulin Glargine 100U/mL
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/490 (5.3%)		23/484 (4.8%)
Blood and lymphatic system disorders
Iron deficiency anaemia	1/490 (0.2%)	1	0/484 (0%)	0
Cardiac disorders
Acute coronary syndrome	0/490 (0%)	0	1/484 (0.2%)	1
Acute myocardial infarction	1/490 (0.2%)	1	0/484 (0%)	0
Atrial fibrillation	1/490 (0.2%)	1	1/484 (0.2%)	1
Bradyarrhythmia	1/490 (0.2%)	1	0/484 (0%)	0
Cardiac failure	1/490 (0.2%)	1	1/484 (0.2%)	1
Cardiac failure congestive	1/490 (0.2%)	1	0/484 (0%)	0
Coronary artery stenosis	0/490 (0%)	0	1/484 (0.2%)	1
Mitral valve incompetence	1/490 (0.2%)	1	0/484 (0%)	0
Myocardial infarction	1/490 (0.2%)	1	0/484 (0%)	0
Palpitations	1/490 (0.2%)	1	0/484 (0%)	0
Congenital, familial and genetic disorders
Arteriovenous malformation	0/490 (0%)	0	1/484 (0.2%)	1
Gastrointestinal disorders
Diabetic gastroparesis	1/490 (0.2%)	1	0/484 (0%)	0
Diarrhoea	0/490 (0%)	0	1/484 (0.2%)	1
Duodenal ulcer	0/490 (0%)	0	1/484 (0.2%)	1
Gastritis	0/490 (0%)	0	1/484 (0.2%)	1
Pancreatic cyst	1/490 (0.2%)	1	0/484 (0%)	0
Upper gastrointestinal haemorrhage	0/490 (0%)	0	1/484 (0.2%)	1
Hepatobiliary disorders
Hyperbilirubinaemia	1/490 (0.2%)	1	0/484 (0%)	0
Infections and infestations
Bronchitis	0/490 (0%)	0	1/484 (0.2%)	1
Hepatitis A	1/490 (0.2%)	1	0/484 (0%)	0
Herpes zoster	0/490 (0%)	0	1/484 (0.2%)	1
Osteomyelitis	0/490 (0%)	0	1/484 (0.2%)	1
Osteomyelitis chronic	0/490 (0%)	0	1/484 (0.2%)	1
Pneumonia	3/490 (0.6%)	3	2/484 (0.4%)	2
Pseudomonas infection	1/490 (0.2%)	1	0/484 (0%)	0
Rhinovirus infection	0/490 (0%)	0	1/484 (0.2%)	1
Sepsis	0/490 (0%)	0	1/484 (0.2%)	1
Urinary tract infection	1/490 (0.2%)	1	0/484 (0%)	0
Injury, poisoning and procedural complications
Contusion	0/490 (0%)	0	1/484 (0.2%)	1
Lower limb fracture	0/490 (0%)	0	1/484 (0.2%)	1
Investigations
Scan myocardial perfusion abnormal	1/490 (0.2%)	1	0/484 (0%)	0
Metabolism and nutrition disorders
Hypoglycaemia	0/490 (0%)	0	1/484 (0.2%)	1
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	0/490 (0%)	0	1/484 (0.2%)	1
Osteoarthritis	1/490 (0.2%)	1	0/484 (0%)	0
Spinal osteoarthritis	0/490 (0%)	0	1/484 (0.2%)	1
Vertebral foraminal stenosis	0/490 (0%)	0	1/484 (0.2%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Myelodysplastic syndrome	1/490 (0.2%)	1	0/484 (0%)	0
Non-Hodgkin's lymphoma	0/490 (0%)	0	1/484 (0.2%)	1
Nervous system disorders
Carotid artery stenosis	1/490 (0.2%)	1	0/484 (0%)	0
Carpal tunnel syndrome	1/490 (0.2%)	1	0/484 (0%)	0
Facial paralysis	1/490 (0.2%)	1	0/484 (0%)	0
Hypoglycaemic unconsciousness	1/490 (0.2%)	1	0/484 (0%)	0
Intercostal neuralgia	0/490 (0%)	0	1/484 (0.2%)	1
Lacunar infarction	0/490 (0%)	0	1/484 (0.2%)	1
Migraine	0/490 (0%)	0	1/484 (0.2%)	1
Renal and urinary disorders
Acute kidney injury	2/490 (0.4%)	2	0/484 (0%)	0
Nephrolithiasis	1/490 (0.2%)	1	1/484 (0.2%)	1
Urinary retention	1/490 (0.2%)	1	0/484 (0%)	0
Reproductive system and breast disorders
Breast mass	0/490 (0%)	0	1/484 (0.2%)	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/490 (0.2%)	1	0/484 (0%)	0
Asthma	1/490 (0.2%)	1	0/484 (0%)	0
Chronic obstructive pulmonary disease	1/490 (0.2%)	2	0/484 (0%)	0
Dyspnoea	1/490 (0.2%)	1	0/484 (0%)	0
Respiratory failure	0/490 (0%)	0	1/484 (0.2%)	1
Surgical and medical procedures
Coronary arterial stent insertion	0/490 (0%)	0	1/484 (0.2%)	1
Vascular disorders
Haematoma	1/490 (0.2%)	1	0/484 (0%)	0
Hypovolaemic shock	0/490 (0%)	0	1/484 (0.2%)	1
Peripheral arterial occlusive disease	0/490 (0%)	0	1/484 (0.2%)	3
Peripheral ischaemia	1/490 (0.2%)	1	0/484 (0%)	0
Other (Not Including Serious) Adverse Events
	Insulin Degludec 100U/mL		Insulin Glargine 100U/mL
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/490 (0%)		0/484 (0%)

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