A 26-week Trial Comparing Efficacy and Safety of Insulin Degludec/Insulin Aspart BID and Insulin Degludec OD Plus Insulin Aspart in Subjects With Type 2 Diabetes Mellitus Treated With Basal Insulin in Need of Treatment Intensification With Mealtime Insulin

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01713530
• Collaborator: (none)
• Enrollment: 274
• Locations: 51
• Arms: 2
• Actual Duration (Months): 10.6
• Patients Per Site: 5.4
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

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

The aim of the trial is to compare the difference in change in glycosylated haemoglobin (HbA1c) between insulin degludec/insulin aspart (IDegAsp) and/or oral anti-diabetic drugs (OADs) and insulin degludec (IDeg) plus insulin aspart (IAsp)and/or OADs.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 274 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 26-week Trial Comparing Efficacy and Safety of Insulin Degludec/Insulin Aspart BID and Insulin Degludec OD Plus Insulin Aspart in Subjects With Type 2 Diabetes Mellitus Treated With Basal Insulin in Need of Treatment Intensification With Mealtime Insulin
• Actual Study Start Date: Feb 21, 2013
• Actual Primary Completion Date: Jan 9, 2014
• Actual Study Completion Date: Jan 9, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IDegAsp BID+/-OADs	Drug: insulin degludec/insulin aspart; Dose individually adjusted. For subcutaneous (s.c, under the skin) administration twice a day.
Experimental: IDeg OD plus IAsp +/-OADs	Drug: insulin degludec; Dose individually adjusted. For subcutaneous (s.c, under the skin) administration once daily.; Drug: insulin aspart; Dose individually adjusted. For subcutaneous (s.c, under the skin) administration with the main meals 2-4 times daily in accordance with local labelling.

Outcome Measures

Primary Outcome Measures

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

   Change from baseline in HbA1c (%) after 26 weeks of treatment

Secondary Outcome Measures

1. Change From Baseline in Fasting Plasma Glucose (FPG) [Week 0, week 26]

   Change from baseline in FPG after 26 weeks of treatment

2. Number of Treatment Emergent Hypoglycaemic Episodes [During Weeks 0-26]

   According to the Novo Nordisk definition for confirmed hypoglycaemic episodes (severe hypoglycaemia and/or a measured Plasma Glucose (PG) <3.1 mmol/L(56 mg/dL))

3. Number of Treatment Emergent Hypoglycaemic Episodes [During Weeks 0-26]

   According to the American Diabetes Association (ADA) definition following are the categories of hypoglycaemic episodes: Severe hypoglycaemia, Documented symptomatic hypoglycaemia, Asymptomatic hypoglycaemia, Probable symptomatic hypoglycaemia and Relative hypoglycaemia

4. Number of Treatment Emergent Nocturnal (00:01-05:59 am) Confirmed Hypoglycaemic Episodes [Weeks 0-26]

   Nocturnal hypoglycaemic episodes are defined as occurring between 00:01 and 05:59 a.m.

5. Incidence of Treatment Emergent Adverse Events (TEAE) [Weeks 0-26]

   A TEAE was defined as an event that has onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Diagnosis of type 2 Diabetes Mellitus at the discretion of the investigator for at least 26 weeks prior to screening (visit 1)

• Treatment with basal insulin for at least 12 weeks prior to randomisation with or without metformin, sulphonylurea (SU)/glinide, DPP-4 inhibitors, alfa-glucosidase-inhibitors

• HbA1c 7.0% - 10.0%

• Body mass index (BMI) less than or equal to 40.0 kg/m^2

Exclusion Criteria:

• Treatment with glucose-lowering agent(s) other than those stated in the inclusion criteria

• Stroke; heart failure New York Heart Association (NYHA) class III or IV; myocardial infarction; unstable angina pectoris; or coronary arterial bypass graft or angioplasty

• Chronic disorder or disease which might jeopardise safety or compliance

• Malignant neoplasms

• Recurrent severe hypoglycaemia

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Greenbrae	California	United States	94904
2	Novo Nordisk Investigational Site	Mission Hills	California	United States	91345
3	Novo Nordisk Investigational Site	San Diego	California	United States	92111
4	Novo Nordisk Investigational Site	Kissimmee	Florida	United States	34741
5	Novo Nordisk Investigational Site	Chicago	Illinois	United States	60607
6	Novo Nordisk Investigational Site	Indianapolis	Indiana	United States	46254
7	Novo Nordisk Investigational Site	Slidell	Louisiana	United States	70461-4231
8	Novo Nordisk Investigational Site	Rockville	Maryland	United States	20852
9	Novo Nordisk Investigational Site	Buckley	Michigan	United States	49620
10	Novo Nordisk Investigational Site	Hillsborough	New Jersey	United States	08844-1225
11	Novo Nordisk Investigational Site	Lawrenceville	New Jersey	United States	08648
12	Novo Nordisk Investigational Site	Toms River	New Jersey	United States	08755-8050
13	Novo Nordisk Investigational Site	Greensboro	North Carolina	United States	27408
14	Novo Nordisk Investigational Site	Whiteville	North Carolina	United States	28472
15	Novo Nordisk Investigational Site	Kettering	Ohio	United States	45429
16	Novo Nordisk Investigational Site	Wadsworth	Ohio	United States	44281-9236
17	Novo Nordisk Investigational Site	Pittsburgh	Pennsylvania	United States	15236
18	Novo Nordisk Investigational Site	Kingsport	Tennessee	United States	37660
19	Novo Nordisk Investigational Site	Austin	Texas	United States	78731
20	Novo Nordisk Investigational Site	Dallas	Texas	United States	75230
21	Novo Nordisk Investigational Site	Dallas	Texas	United States	75246
22	Novo Nordisk Investigational Site	Houston	Texas	United States	77024
23	Novo Nordisk Investigational Site	Round Rock	Texas	United States	78681
24	Novo Nordisk Investigational Site	San Antonio	Texas	United States	78224
25	Novo Nordisk Investigational Site	Tacoma	Washington	United States	98405
26	Novo Nordisk Investigational Site	Martinsburg	West Virginia	United States	25401
27	Novo Nordisk Investigational Site	Algiers		Algeria
28	Novo Nordisk Investigational Site	Annaba		Algeria
29	Novo Nordisk Investigational Site	Constantine		Algeria	25000
30	Novo Nordisk Investigational Site	Oran		Algeria	31000
31	Novo Nordisk Investigational Site	Graz		Austria	8036
32	Novo Nordisk Investigational Site	Innsbruck		Austria	6020
33	Novo Nordisk Investigational Site	Linz		Austria	4021
34	Novo Nordisk Investigational Site	Mödling		Austria	2340
35	Novo Nordisk Investigational Site	Salzburg		Austria	5010
36	Novo Nordisk Investigational Site	Wien		Austria	1090
37	Novo Nordisk Investigational Site	Wien		Austria	1130
38	Novo Nordisk Investigational Site	Caen		France	14033
39	Novo Nordisk Investigational Site	LA ROCHE-sur-YON cedex 9		France	85295
40	Novo Nordisk Investigational Site	LA ROCHELLE cedex		France	17019
41	Novo Nordisk Investigational Site	Le Creusot		France	71200
42	Novo Nordisk Investigational Site	Montpellier		France	34000
43	Novo Nordisk Investigational Site	Montpellier		France	34070
44	Novo Nordisk Investigational Site	Saint Herblain		France	44800
45	Novo Nordisk Investigational Site	Venissieux		France	69200
46	Novo Nordisk Investigational Site	Hamar		Norway	2317
47	Novo Nordisk Investigational Site	Kongsvinger		Norway	2212
48	Novo Nordisk Investigational Site	Kristiansand S		Norway	4604
49	Novo Nordisk Investigational Site	Oslo		Norway	0586
50	Novo Nordisk Investigational Site	Skedsmokorset		Norway	NO-2020
51	Novo Nordisk Investigational Site	Stavanger		Norway	4011

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: NCT01713530
• Other Study ID Numbers: NN5401-3996; 2012-002346-20; U1111-1130-7135
• First Posted: Oct 24, 2012
• Last Update Posted: Apr 2, 2018
• Last Verified: Mar 1, 2018

• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Insulin; Insulin, Globin Zinc; Insulin Aspart; Insulin, Long-Acting; Insulin degludec, insulin aspart drug combination

Study Results

Participant Flow

Recruitment Details	The trial was conducted in 5 countries (48 sites): Algeria (4), Austria (6), France (8), Norway (6) and United States (24).

Arm/Group Title	IDegAsp BID	IDeg OD+IAsp
Arm/Group Description	The subjects in this arm received insulin degludec/insulin aspart (IDegAsp) (100 U/mL, 3 mL prefilled pen PDS290) twice daily, subcutaneously in the abdomen, upper arm (deltoid area) or thigh either with breakfast and dinner or with lunch and dinner for 26 weeks. The subjects pre-study medication included a basal insulin regimen (insulin detemir; insulin glargine; insulin NPH) with or without oral anti-diabetic drugs (OADs) (metformin, sulphonylurea (SU), glinide, dipeptidyl peptidase-4 (DPP-4) inhibitors, α-glucosidase-inhibitors), for at least 12 weeks prior to visit 1 (screening).	The subjects in this arm received IDeg (100 U/mL, 3 mL prefilled pen PDS290) once daily, subcutaneously in the abdomen, upper arm (deltoid area) or thigh at any time of the day. The subjects in this arm also received IAsp ([NovoRapid®/NovoLog®], 100 U/mL, 3 mL, FlexPen®) with the main meals 2-4 times daily, subcutaneously (preferably into the abdominal wall) in accordance with local labelling. The subjects pre-study medication included a basal insulin regimen (insulin detemir; insulin glargine; insulin NPH) with or without OADs (metformin, SU, glinide, DPP-4 inhibitors, α-glucosidase-inhibitors), for at least 12 weeks prior to visit 1.
Period Title: Overall Study
STARTED	138	136
Exposed	136	135
COMPLETED	113	117
NOT COMPLETED	25	19

Baseline Characteristics

Arm/Group Title	IDegAsp BID	IDeg OD+IAsp	Total
Arm/Group Description	The subjects in this arm received insulin degludec/insulin aspart (IDegAsp) (100 U/mL, 3 mL prefilled pen PDS290) twice daily, subcutaneously in the abdomen, upper arm (deltoid area) or thigh either with breakfast and dinner or with lunch and dinner for 26 weeks. The subjects pre-study medication included a basal insulin regimen (insulin detemir; insulin glargine; insulin NPH) with or without oral anti-diabetic drugs (OADs) (metformin, sulphonylurea (SU), glinide, dipeptidyl peptidase-4 (DPP-4) inhibitors, α-glucosidase-inhibitors), for at least 12 weeks prior to visit 1 (screening).	The subjects in this arm received IDeg (100 U/mL, 3 mL prefilled pen PDS290) once daily, subcutaneously in the abdomen, upper arm (deltoid area) or thigh at any time of the day. The subjects in this arm also received IAsp ([NovoRapid®/NovoLog®], 100 U/mL, 3 mL, FlexPen®) with the main meals 2-4 times daily, subcutaneously (preferably into the abdominal wall) in accordance with local labelling. The subjects pre-study medication included a basal insulin regimen (insulin detemir; insulin glargine; insulin NPH) with or without OADs (metformin, SU, glinide, DPP-4 inhibitors, α-glucosidase-inhibitors), for at least 12 weeks prior to visit 1.	Total of all reporting groups
Overall Participants	138	136	274
Age (years) [Mean (Standard Deviation) ]
Age	59.6 (8.3)	59.6 (9.2)	59.6 (8.7)
Sex: Female, Male (Count of Participants)
Female	65 47.1%	50 36.8%	115 42%
Male	73 52.9%	86 63.2%	159 58%
Glycosylated haemoglobin (HbA1c) (percentage of glycosylated haemoglobin) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of glycosylated haemoglobin]	8.3 (0.9)	8.3 (0.7)	8.3 (0.8)
Fasting plasma glucose (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	9.0 (3.0)	8.8 (2.9)	8.9 (3.0)

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

The FAS included all randomised subjects. The statistical evaluation of the FAS followed the ITT principle and subjects contributed to the evaluation "as randomised".

Arm/Group Title	IDegAsp BID	IDeg OD+IAsp
Arm/Group Description	The subjects in this arm received insulin degludec/insulin aspart (IDegAsp) (100 U/mL, 3 mL prefilled pen PDS290) twice daily, subcutaneously in the abdomen, upper arm (deltoid area) or thigh either with breakfast and dinner or with lunch and dinner for 26 weeks. The subjects pre-study medication included a basal insulin regimen (insulin detemir; insulin glargine; insulin NPH) with or without oral anti-diabetic drugs (OADs) (metformin, sulphonylurea (SU), glinide, dipeptidyl peptidase-4 (DPP-4) inhibitors, α-glucosidase-inhibitors), for at least 12 weeks prior to visit 1 (screening).	The subjects in this arm received IDeg (100 U/mL, 3 mL prefilled pen PDS290) once daily, subcutaneously in the abdomen, upper arm (deltoid area) or thigh at any time of the day. The subjects in this arm also received IAsp ([NovoRapid®/NovoLog®], 100 U/mL, 3 mL, FlexPen®) with the main meals 2-4 times daily, subcutaneously (preferably into the abdominal wall) in accordance with local labelling. The subjects pre-study medication included a basal insulin regimen (insulin detemir; insulin glargine; insulin NPH) with or without OADs (metformin, SU, glinide, DPP-4 inhibitors, α-glucosidase-inhibitors), for at least 12 weeks prior to visit 1.
Measure Participants	138	136
Least Squares Mean (Standard Error) [percentage change in HbA1c]	-1.23 (0.13)	-1.42 (0.12)

2. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose (FPG)
Description	Change from baseline in FPG after 26 weeks of treatment
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

The FAS included all randomised subjects (2 subjects-baseline FPG not measured). The statistical evaluation of the FAS followed the ITT principle and subjects contributed to the evaluation "as randomised".

Arm/Group Title	IDegAsp BID	IDeg OD+IAsp
Arm/Group Description	The subjects in this arm received insulin degludec/insulin aspart (IDegAsp) (100 U/mL, 3 mL prefilled pen PDS290) twice daily, subcutaneously in the abdomen, upper arm (deltoid area) or thigh either with breakfast and dinner or with lunch and dinner for 26 weeks. The subjects pre-study medication included a basal insulin regimen (insulin detemir; insulin glargine; insulin NPH) with or without oral anti-diabetic drugs (OADs) (metformin, sulphonylurea (SU), glinide, dipeptidyl peptidase-4 (DPP-4) inhibitors, α-glucosidase-inhibitors), for at least 12 weeks prior to visit 1 (screening).	The subjects in this arm received IDeg (100 U/mL, 3 mL prefilled pen PDS290) once daily, subcutaneously in the abdomen, upper arm (deltoid area) or thigh at any time of the day. The subjects in this arm also received IAsp ([NovoRapid®/NovoLog®], 100 U/mL, 3 mL, FlexPen®) with the main meals 2-4 times daily, subcutaneously (preferably into the abdominal wall) in accordance with local labelling. The subjects pre-study medication included a basal insulin regimen (insulin detemir; insulin glargine; insulin NPH) with or without OADs (metformin, SU, glinide, DPP-4 inhibitors, α-glucosidase-inhibitors), for at least 12 weeks prior to visit 1.
Measure Participants	136	136
Least Squares Mean (Standard Error) [mmol/L]	-2.22 (0.38)	-1.90 (0.36)

3. Secondary Outcome

Title	Number of Treatment Emergent Hypoglycaemic Episodes
Description	According to the Novo Nordisk definition for confirmed hypoglycaemic episodes (severe hypoglycaemia and/or a measured Plasma Glucose (PG) <3.1 mmol/L(56 mg/dL))
Time Frame	During Weeks 0-26

Outcome Measure Data

Analysis Population Description

The safety Analysis Set (SAS): included all subjects who received at least one dose of the investigational product or its comparator. Subjects in the safety set contributed to the evaluation "as treated".

Arm/Group Title	IDegAsp BID	IDeg OD+IAsp
Arm/Group Description	The subjects in this arm received insulin degludec/insulin aspart (IDegAsp) (100 U/mL, 3 mL prefilled pen PDS290) twice daily, subcutaneously in the abdomen, upper arm (deltoid area) or thigh either with breakfast and dinner or with lunch and dinner for 26 weeks. The subjects pre-study medication included a basal insulin regimen (insulin detemir; insulin glargine; insulin NPH) with or without oral anti-diabetic drugs (OADs) (metformin, sulphonylurea (SU), glinide, dipeptidyl peptidase-4 (DPP-4) inhibitors, α-glucosidase-inhibitors), for at least 12 weeks prior to visit 1 (screening).	The subjects in this arm received IDeg (100 U/mL, 3 mL prefilled pen PDS290) once daily, subcutaneously in the abdomen, upper arm (deltoid area) or thigh at any time of the day. The subjects in this arm also received IAsp ([NovoRapid®/NovoLog®], 100 U/mL, 3 mL, FlexPen®) with the main meals 2-4 times daily, subcutaneously (preferably into the abdominal wall) in accordance with local labelling. The subjects pre-study medication included a basal insulin regimen (insulin detemir; insulin glargine; insulin NPH) with or without OADs (metformin, SU, glinide, DPP-4 inhibitors, α-glucosidase-inhibitors), for at least 12 weeks prior to visit 1.
Measure Participants	136	135
Number [episodes]	706	841

4. Secondary Outcome

Title	Number of Treatment Emergent Hypoglycaemic Episodes
Description	According to the American Diabetes Association (ADA) definition following are the categories of hypoglycaemic episodes: Severe hypoglycaemia, Documented symptomatic hypoglycaemia, Asymptomatic hypoglycaemia, Probable symptomatic hypoglycaemia and Relative hypoglycaemia
Time Frame	During Weeks 0-26

Outcome Measure Data

Analysis Population Description

The SAS included all subjects who received at least one dose of the investigational product or its comparator. Subjects in the safety set contributed to the evaluation "as treated".

Arm/Group Title	IDegAsp BID	IDeg OD+IAsp
Arm/Group Description	The subjects in this arm received insulin degludec/insulin aspart (IDegAsp) (100 U/mL, 3 mL prefilled pen PDS290) twice daily, subcutaneously in the abdomen, upper arm (deltoid area) or thigh either with breakfast and dinner or with lunch and dinner for 26 weeks. The subjects pre-study medication included a basal insulin regimen (insulin detemir; insulin glargine; insulin NPH) with or without oral anti-diabetic drugs (OADs) (metformin, sulphonylurea (SU), glinide, dipeptidyl peptidase-4 (DPP-4) inhibitors, α-glucosidase-inhibitors), for at least 12 weeks prior to visit 1 (screening).	The subjects in this arm received IDeg (100 U/mL, 3 mL prefilled pen PDS290) once daily, subcutaneously in the abdomen, upper arm (deltoid area) or thigh at any time of the day. The subjects in this arm also received IAsp ([NovoRapid®/NovoLog®], 100 U/mL, 3 mL, FlexPen®) with the main meals 2-4 times daily, subcutaneously (preferably into the abdominal wall) in accordance with local labelling. The subjects pre-study medication included a basal insulin regimen (insulin detemir; insulin glargine; insulin NPH) with or without OADs (metformin, SU, glinide, DPP-4 inhibitors, α-glucosidase-inhibitors), for at least 12 weeks prior to visit 1.
Measure Participants	136	135
ADA (American Diabetes Association)	2894	2685
Severe	29	15
Documented symptomatic	1818	1843
Asymptomatic	930	728
Probable symptomatic	26	33
Relative	91	66

5. Secondary Outcome

Title	Number of Treatment Emergent Nocturnal (00:01-05:59 am) Confirmed Hypoglycaemic Episodes
Description	Nocturnal hypoglycaemic episodes are defined as occurring between 00:01 and 05:59 a.m.
Time Frame	Weeks 0-26

Outcome Measure Data

Analysis Population Description

The SAS included all subjects who received at least one dose of the investigational product or its comparator. Subjects in the safety set contributed to the evaluation "as treated".

Arm/Group Title	IDegAsp BID	IDeg OD+IAsp
Arm/Group Description	The subjects in this arm received insulin degludec/insulin aspart (IDegAsp) (100 U/mL, 3 mL prefilled pen PDS290) twice daily, subcutaneously in the abdomen, upper arm (deltoid area) or thigh either with breakfast and dinner or with lunch and dinner for 26 weeks. The subjects pre-study medication included a basal insulin regimen (insulin detemir; insulin glargine; insulin NPH) with or without oral anti-diabetic drugs (OADs) (metformin, sulphonylurea (SU), glinide, dipeptidyl peptidase-4 (DPP-4) inhibitors, α-glucosidase-inhibitors), for at least 12 weeks prior to visit 1 (screening).	The subjects in this arm received IDeg (100 U/mL, 3 mL prefilled pen PDS290) once daily, subcutaneously in the abdomen, upper arm (deltoid area) or thigh at any time of the day. The subjects in this arm also received IAsp ([NovoRapid®/NovoLog®], 100 U/mL, 3 mL, FlexPen®) with the main meals 2-4 times daily, subcutaneously (preferably into the abdominal wall) in accordance with local labelling. The subjects pre-study medication included a basal insulin regimen (insulin detemir; insulin glargine; insulin NPH) with or without OADs (metformin, SU, glinide, DPP-4 inhibitors, α-glucosidase-inhibitors), for at least 12 weeks prior to visit 1.
Measure Participants	136	135
Number [episodes]	75	96

6. Secondary Outcome

Title	Incidence of Treatment Emergent Adverse Events (TEAE)
Description	A TEAE was defined as an event that has onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment
Time Frame	Weeks 0-26

Outcome Measure Data

Analysis Population Description

The SAS included all subjects who received at least one dose of the investigational product or its comparator. Subjects in the safety set contributed to the evaluation "as treated".

Arm/Group Title	IDegAsp BID	IDeg OD+IAsp
Arm/Group Description	The subjects in this arm received insulin degludec/insulin aspart (IDegAsp) (100 U/mL, 3 mL prefilled pen PDS290) twice daily, subcutaneously in the abdomen, upper arm (deltoid area) or thigh either with breakfast and dinner or with lunch and dinner for 26 weeks. The subjects pre-study medication included a basal insulin regimen (insulin detemir; insulin glargine; insulin NPH) with or without oral anti-diabetic drugs (OADs) (metformin, sulphonylurea (SU), glinide, dipeptidyl peptidase-4 (DPP-4) inhibitors, α-glucosidase-inhibitors), for at least 12 weeks prior to visit 1 (screening).	The subjects in this arm received IDeg (100 U/mL, 3 mL prefilled pen PDS290) once daily, subcutaneously in the abdomen, upper arm (deltoid area) or thigh at any time of the day. The subjects in this arm also received IAsp ([NovoRapid®/NovoLog®], 100 U/mL, 3 mL, FlexPen®) with the main meals 2-4 times daily, subcutaneously (preferably into the abdominal wall) in accordance with local labelling. The subjects pre-study medication included a basal insulin regimen (insulin detemir; insulin glargine; insulin NPH) with or without OADs (metformin, SU, glinide, DPP-4 inhibitors, α-glucosidase-inhibitors), for at least 12 weeks prior to visit 1.
Measure Participants	136	135
Number [number of events]	330	298

Adverse Events

Time Frame	The adverse events (AEs) were collected for a duration of 28 weeks ie. from the first trial-related activity after the subject had signed the informed consent until the end of the post-treatment follow-up period (visit 29).
Adverse Event Reporting Description	The SAS included all subjects who received at least one dose of the investigational product or its comparator. Subjects in the safety set contributed to the evaluation "as treated".
Arm/Group Title	IDegAsp BID		IDeg OD+IAsp
Arm/Group Description	The subjects in this arm received insulin degludec/insulin aspart (IDegAsp) (100 U/mL, 3 mL prefilled pen PDS290) twice daily, subcutaneously in the abdomen, upper arm (deltoid area) or thigh either with breakfast and dinner or with lunch and dinner for 26 weeks. The subjects pre-study medication included a basal insulin regimen (insulin detemir; insulin glargine; insulin NPH) with or without oral anti-diabetic drugs (OADs) (metformin, sulphonylurea (SU), glinide, dipeptidyl peptidase-4 (DPP-4) inhibitors, α-glucosidase-inhibitors), for at least 12 weeks prior to visit 1 (screening).		The subjects in this arm received IDeg (100 U/mL, 3 mL prefilled pen PDS290) once daily, subcutaneously in the abdomen, upper arm (deltoid area) or thigh at any time of the day. The subjects in this arm also received IAsp ([NovoRapid®/NovoLog®], 100 U/mL, 3 mL, FlexPen®) with the main meals 2-4 times daily, subcutaneously (preferably into the abdominal wall) in accordance with local labelling. The subjects pre-study medication included a basal insulin regimen (insulin detemir; insulin glargine; insulin NPH) with or without OADs (metformin, SU, glinide, DPP-4 inhibitors, α-glucosidase-inhibitors), for at least 12 weeks prior to visit 1.
All Cause Mortality
	IDegAsp BID		IDeg OD+IAsp
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	IDegAsp BID		IDeg OD+IAsp
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/136 (5.1%)		13/135 (9.6%)
Cardiac disorders
Angina pectoris	1/136 (0.7%)	1	0/135 (0%)	0
Atrioventricular block complete	1/136 (0.7%)	1	0/135 (0%)	0
Eye disorders
Ocular hypertension	0/136 (0%)	0	1/135 (0.7%)	1
General disorders
Chest pain	1/136 (0.7%)	1	0/135 (0%)	0
Injury, poisoning and procedural complications
Femoral neck fracture	1/136 (0.7%)	1	0/135 (0%)	0
Rib fracture	0/136 (0%)	0	1/135 (0.7%)	1
Road traffic accident	0/136 (0%)	0	2/135 (1.5%)	2
Wrong drug administered	0/136 (0%)	0	2/135 (1.5%)	2
Metabolism and nutrition disorders
Hypoglycaemia	1/136 (0.7%)	1	2/135 (1.5%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pituitary tumour benign	0/136 (0%)	0	1/135 (0.7%)	1
Prostate cancer	0/136 (0%)	0	1/135 (0.7%)	1
Nervous system disorders
Hypersomnia	1/136 (0.7%)	1	0/135 (0%)	0
Hypoglycaemic unconsciousness	1/136 (0.7%)	1	1/135 (0.7%)	1
Psychiatric disorders
Depression	0/136 (0%)	0	1/135 (0.7%)	1
Suicidal ideation	0/136 (0%)	0	1/135 (0.7%)	1
Respiratory, thoracic and mediastinal disorders
Pneumomediastinum	0/136 (0%)	0	1/135 (0.7%)	1
Pneumothorax	0/136 (0%)	0	1/135 (0.7%)	1
Vascular disorders
Thrombosis	0/136 (0%)	0	1/135 (0.7%)	1
Other (Not Including Serious) Adverse Events
	IDegAsp BID		IDeg OD+IAsp
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	46/136 (33.8%)		38/135 (28.1%)
Gastrointestinal disorders
Diarrhoea	9/136 (6.6%)	9	9/135 (6.7%)	9
General disorders
Asthenia	10/136 (7.4%)	10	2/135 (1.5%)	2
Fatigue	7/136 (5.1%)	7	1/135 (0.7%)	1
Infections and infestations
Influenza	9/136 (6.6%)	9	5/135 (3.7%)	7
Nasopharyngitis	11/136 (8.1%)	11	12/135 (8.9%)	14
Musculoskeletal and connective tissue disorders
Back pain	5/136 (3.7%)	5	7/135 (5.2%)	8
Pain in extremity	8/136 (5.9%)	8	3/135 (2.2%)	3
Nervous system disorders
Headache	10/136 (7.4%)	12	8/135 (5.9%)	12

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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