Trial Outcomes & Findings for A 38 Week Trial Comparing Effect and Safety of Insulin Degludec/Insulin Aspart vs. Insulin Glargine Plus Insulin Aspart in Subjects With Type 2 Diabetes Treated With Basal Insulin With or Without Oral Antidiabetic Treatment in Need of Treatment Intensification (NCT NCT02906917)

NCT ID: NCT02906917

Last Updated: 2019-11-13

Results Overview

Change from baseline (week 0) in glycosylated haemoglobin (HbA1c) was evaluated 26 weeks after randomisation.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 532 participants
• Primary outcome timeframe: Week 0, week 26
• Results posted on: 2019-11-13

Participant Flow

The trial was conducted at 71 sites in 7 countries, as follows: Algeria (4), Czech Republic (6), India (10), Russian Federation (11), Serbia (5), Turkey (7), and United States (28). Additionally, 1 site in the United States screened, but didn't randomise any subject.

Participant milestones

Measure	Insulin Degludec/Insulin Aspart Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): Insulin degludec/insulin aspart (IDegAsp) once daily (OD) administered at the largest meal each day with or without oral antidiabetic drug(s) (OAD(s)). Subjects switching from pre-trial basal insulin OD or more to IDegAsp OD at trial entry were to transfer unit-to-unit. 2) Intensification period (period-2, week 26-38): IDegAsp OD/twice a day (BID) administered at the largest meal(s) each day (in the case of BID dosing, one meal being dinner) based on individual needs with or without OAD(s).	Insulin Glargine + Insulin Aspart Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): Insulin glargine (IGlar) OD administered in accordance with local labelling and insulin aspart (IAsp) OD administered at the largest meal with or without OAD(s). Subjects switching from pre-trial basal insulin OD to IGlar OD were also to transfer unit-to-unit to IGlar, while subjects switching from basal insulin more than OD to IGlar OD were to reduce the initial total daily dose by 20% or according to local labelling. IAsp was to be initiated at 4 units with the largest meal. 2) Intensification period (period-2, week 26-38): IGlar OD administered in accordance with local labelling and IAsp 1-3 times daily administered at main meals based on individual needs with or without OAD(s).
Initiation Period (Week 0-26) STARTED	267	265
Initiation Period (Week 0-26) Exposed	265	263
Initiation Period (Week 0-26) COMPLETED	261	254
Initiation Period (Week 0-26) NOT COMPLETED	6	11
Intensification Period (Week 26-38) STARTED	261	254
Intensification Period (Week 26-38) COMPLETED	252	247
Intensification Period (Week 26-38) NOT COMPLETED	9	7

Reasons for withdrawal

Measure	Insulin Degludec/Insulin Aspart Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): Insulin degludec/insulin aspart (IDegAsp) once daily (OD) administered at the largest meal each day with or without oral antidiabetic drug(s) (OAD(s)). Subjects switching from pre-trial basal insulin OD or more to IDegAsp OD at trial entry were to transfer unit-to-unit. 2) Intensification period (period-2, week 26-38): IDegAsp OD/twice a day (BID) administered at the largest meal(s) each day (in the case of BID dosing, one meal being dinner) based on individual needs with or without OAD(s).	Insulin Glargine + Insulin Aspart Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): Insulin glargine (IGlar) OD administered in accordance with local labelling and insulin aspart (IAsp) OD administered at the largest meal with or without OAD(s). Subjects switching from pre-trial basal insulin OD to IGlar OD were also to transfer unit-to-unit to IGlar, while subjects switching from basal insulin more than OD to IGlar OD were to reduce the initial total daily dose by 20% or according to local labelling. IAsp was to be initiated at 4 units with the largest meal. 2) Intensification period (period-2, week 26-38): IGlar OD administered in accordance with local labelling and IAsp 1-3 times daily administered at main meals based on individual needs with or without OAD(s).
Initiation Period (Week 0-26) Unclassified	1	3
Initiation Period (Week 0-26) Adverse Event	1	0
Initiation Period (Week 0-26) Lost to Follow-up	1	4
Initiation Period (Week 0-26) Withdrawal by Subject	3	4
Intensification Period (Week 26-38) Unclassified	3	2
Intensification Period (Week 26-38) Adverse Event	0	2
Intensification Period (Week 26-38) Lost to Follow-up	3	1
Intensification Period (Week 26-38) Withdrawal by Subject	3	2

Baseline Characteristics

A 38 Week Trial Comparing Effect and Safety of Insulin Degludec/Insulin Aspart vs. Insulin Glargine Plus Insulin Aspart in Subjects With Type 2 Diabetes Treated With Basal Insulin With or Without Oral Antidiabetic Treatment in Need of Treatment Intensification

Baseline characteristics by cohort

Measure	Insulin Degludec/Insulin Aspart n=267 Participants Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): IDegAsp OD administered at the largest meal each day with or without OAD(s). Subjects switching from pre-trial basal insulin OD or more to IDegAsp OD at trial entry were to transfer unit-to-unit. 2) Intensification period (period-2, week 26-38): IDegAsp OD/BID administered at the largest meal(s) each day (in the case of BID dosing, one meal being dinner) based on individual needs with or without OAD(s).	Insulin Glargine + Insulin Aspart n=265 Participants Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): Insulin glargine (IGlar) OD administered in accordance with local labelling and insulin aspart (IAsp) OD administered at the largest meal with or without OAD(s). Subjects switching from pre-trial basal insulin OD to IGlar OD were also to transfer unit-to-unit to IGlar, while subjects switching from basal insulin more than OD to IGlar OD were to reduce the initial total daily dose by 20% or according to local labelling. IAsp was to be initiated at 4 units with the largest meal. 2) Intensification period (period-2, week 26-38): IGlar OD administered in accordance with local labelling and IAsp 1-3 times daily administered at main meals based on individual needs with or without OAD(s).	Total n=532 Participants Total of all reporting groups
Age, Continuous	58.2 Years STANDARD_DEVIATION 8.9 • n=5 Participants	59.2 Years STANDARD_DEVIATION 9.1 • n=7 Participants	58.7 Years STANDARD_DEVIATION 9.0 • n=5 Participants
Sex: Female, Male Female	142 Participants n=5 Participants	128 Participants n=7 Participants	270 Participants n=5 Participants
Sex: Female, Male Male	125 Participants n=5 Participants	137 Participants n=7 Participants	262 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	21 Participants n=5 Participants	20 Participants n=7 Participants	41 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	246 Participants n=5 Participants	245 Participants n=7 Participants	491 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	29 Participants n=5 Participants	32 Participants n=7 Participants	61 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	13 Participants n=5 Participants	11 Participants n=7 Participants	24 Participants n=5 Participants
Race (NIH/OMB) White	221 Participants n=5 Participants	220 Participants n=7 Participants	441 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 0, week 26

Population: FAS, which included all randomised subjects. Number of subjects analyzed = number of subjects contributed to the analysis at specified time point.

Change from baseline (week 0) in glycosylated haemoglobin (HbA1c) was evaluated 26 weeks after randomisation.

Outcome measures

Measure	Insulin Degludec/Insulin Aspart n=267 Participants Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): IDegAsp OD administered at the largest meal each day with or without OAD(s). Subjects switching from pre-trial basal insulin OD or more to IDegAsp OD at trial entry were to transfer unit-to-unit. 2) Intensification period (period-2, week 26-38): IDegAsp OD/BID administered at the largest meal(s) each day (in the case of BID dosing, one meal being dinner) based on individual needs with or without OAD(s).	Insulin Glargine + Insulin Aspart n=265 Participants Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): Insulin glargine (IGlar) OD administered in accordance with local labelling and insulin aspart (IAsp) OD administered at the largest meal with or without OAD(s). Subjects switching from pre-trial basal insulin OD to IGlar OD were also to transfer unit-to-unit to IGlar, while subjects switching from basal insulin more than OD to IGlar OD were to reduce the initial total daily dose by 20% or according to local labelling. IAsp was to be initiated at 4 units with the largest meal. 2) Intensification period (period-2, week 26-38): IGlar OD administered in accordance with local labelling and IAsp 1-3 times daily administered at main meals based on individual needs with or without OAD(s).
Change in HbA1c (%) - Week 26 Baseline (week 0)	8.2 % of HbA1c Standard Deviation 0.8	8.1 % of HbA1c Standard Deviation 0.7
Change in HbA1c (%) - Week 26 Change from baseline (week 26)	-1.1 % of HbA1c Standard Deviation 0.9	-1.1 % of HbA1c Standard Deviation 0.8

SECONDARY outcome

Timeframe: Week 0, week 38

Population: FAS, which included all randomised subjects. Number of subjects analyzed = number of subjects contributed to the analysis at specified time point.

Change from baseline (week 0) in HbA1c was evaluated 38 weeks after randomisation.

Outcome measures

Measure	Insulin Degludec/Insulin Aspart n=267 Participants Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): IDegAsp OD administered at the largest meal each day with or without OAD(s). Subjects switching from pre-trial basal insulin OD or more to IDegAsp OD at trial entry were to transfer unit-to-unit. 2) Intensification period (period-2, week 26-38): IDegAsp OD/BID administered at the largest meal(s) each day (in the case of BID dosing, one meal being dinner) based on individual needs with or without OAD(s).	Insulin Glargine + Insulin Aspart n=265 Participants Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): Insulin glargine (IGlar) OD administered in accordance with local labelling and insulin aspart (IAsp) OD administered at the largest meal with or without OAD(s). Subjects switching from pre-trial basal insulin OD to IGlar OD were also to transfer unit-to-unit to IGlar, while subjects switching from basal insulin more than OD to IGlar OD were to reduce the initial total daily dose by 20% or according to local labelling. IAsp was to be initiated at 4 units with the largest meal. 2) Intensification period (period-2, week 26-38): IGlar OD administered in accordance with local labelling and IAsp 1-3 times daily administered at main meals based on individual needs with or without OAD(s).
Change in HbA1c (%) - Week 38 Baseline (week 0)	8.2 % of HbA1c Standard Deviation 0.8	8.1 % of HbA1c Standard Deviation 0.7
Change in HbA1c (%) - Week 38 Change from baseline (week 38)	-1.2 % of HbA1c Standard Deviation 0.9	-1.2 % of HbA1c Standard Deviation 0.9

SECONDARY outcome

Timeframe: Week 26 and week 38

Population: FAS, which included all randomised subjects. Number of subjects analyzed = number of subjects contributed to the analysis at specified time point.

Participants achieving (yes/no) HbA1c <7% was evaluated 26 and 38 weeks after randomisation, respectively.

Outcome measures

Measure	Insulin Degludec/Insulin Aspart n=267 Participants Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): IDegAsp OD administered at the largest meal each day with or without OAD(s). Subjects switching from pre-trial basal insulin OD or more to IDegAsp OD at trial entry were to transfer unit-to-unit. 2) Intensification period (period-2, week 26-38): IDegAsp OD/BID administered at the largest meal(s) each day (in the case of BID dosing, one meal being dinner) based on individual needs with or without OAD(s).	Insulin Glargine + Insulin Aspart n=265 Participants Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): Insulin glargine (IGlar) OD administered in accordance with local labelling and insulin aspart (IAsp) OD administered at the largest meal with or without OAD(s). Subjects switching from pre-trial basal insulin OD to IGlar OD were also to transfer unit-to-unit to IGlar, while subjects switching from basal insulin more than OD to IGlar OD were to reduce the initial total daily dose by 20% or according to local labelling. IAsp was to be initiated at 4 units with the largest meal. 2) Intensification period (period-2, week 26-38): IGlar OD administered in accordance with local labelling and IAsp 1-3 times daily administered at main meals based on individual needs with or without OAD(s).
Responder (Yes/No) for HbA1c < 7% Week 26: Yes	120 Number of participants	120 Number of participants
Responder (Yes/No) for HbA1c < 7% Week 26: No	121 Number of participants	122 Number of participants
Responder (Yes/No) for HbA1c < 7% Week 38: Yes	139 Number of participants	140 Number of participants
Responder (Yes/No) for HbA1c < 7% Week 38: No	95 Number of participants	93 Number of participants

SECONDARY outcome

Timeframe: Week 26 and week 38

Population: FAS, which included all randomised subjects. Number of subjects analyzed = number of subjects contributed to the analysis at specified time point.

Participants achieving (yes/no) HbA1c <7% without severe or blood glucose (BG) confirmed symptomatic hypoglycaemia, was evaluated 26 and 38 weeks after randomisation, respectively. Severe or BG confirmed symptomatic hypoglycaemia: An episode that is severe according to the American Diabetes Association (ADA) classification or BG confirmed by a plasma glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. Severe hypoglycaemia as per ADA classification: An episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. Plasma glucose concentrations 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.

Outcome measures

Measure	Insulin Degludec/Insulin Aspart n=267 Participants Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): IDegAsp OD administered at the largest meal each day with or without OAD(s). Subjects switching from pre-trial basal insulin OD or more to IDegAsp OD at trial entry were to transfer unit-to-unit. 2) Intensification period (period-2, week 26-38): IDegAsp OD/BID administered at the largest meal(s) each day (in the case of BID dosing, one meal being dinner) based on individual needs with or without OAD(s).	Insulin Glargine + Insulin Aspart n=265 Participants Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): Insulin glargine (IGlar) OD administered in accordance with local labelling and insulin aspart (IAsp) OD administered at the largest meal with or without OAD(s). Subjects switching from pre-trial basal insulin OD to IGlar OD were also to transfer unit-to-unit to IGlar, while subjects switching from basal insulin more than OD to IGlar OD were to reduce the initial total daily dose by 20% or according to local labelling. IAsp was to be initiated at 4 units with the largest meal. 2) Intensification period (period-2, week 26-38): IGlar OD administered in accordance with local labelling and IAsp 1-3 times daily administered at main meals based on individual needs with or without OAD(s).
Responder (Yes/No) for HbA1c <7% Without Severe or BG Confirmed Symptomatic Hypoglycaemia Week 26: Yes	73 Number of participants	61 Number of participants
Responder (Yes/No) for HbA1c <7% Without Severe or BG Confirmed Symptomatic Hypoglycaemia Week 26: No	168 Number of participants	181 Number of participants
Responder (Yes/No) for HbA1c <7% Without Severe or BG Confirmed Symptomatic Hypoglycaemia Week 38: Yes	60 Number of participants	56 Number of participants
Responder (Yes/No) for HbA1c <7% Without Severe or BG Confirmed Symptomatic Hypoglycaemia Week 38: No	174 Number of participants	177 Number of participants

SECONDARY outcome

Timeframe: Week 0, week 26, week 38

Population: FAS, which included all randomised subjects. Number of subjects analyzed = number of subjects contributed to the analysis at specified time point.

Change from baseline (week 0) in fasting plasma glucose (FPG) was evaluated 26 and 38 weeks after randomisation, respectively.

Outcome measures

Measure	Insulin Degludec/Insulin Aspart n=267 Participants Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): IDegAsp OD administered at the largest meal each day with or without OAD(s). Subjects switching from pre-trial basal insulin OD or more to IDegAsp OD at trial entry were to transfer unit-to-unit. 2) Intensification period (period-2, week 26-38): IDegAsp OD/BID administered at the largest meal(s) each day (in the case of BID dosing, one meal being dinner) based on individual needs with or without OAD(s).	Insulin Glargine + Insulin Aspart n=265 Participants Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): Insulin glargine (IGlar) OD administered in accordance with local labelling and insulin aspart (IAsp) OD administered at the largest meal with or without OAD(s). Subjects switching from pre-trial basal insulin OD to IGlar OD were also to transfer unit-to-unit to IGlar, while subjects switching from basal insulin more than OD to IGlar OD were to reduce the initial total daily dose by 20% or according to local labelling. IAsp was to be initiated at 4 units with the largest meal. 2) Intensification period (period-2, week 26-38): IGlar OD administered in accordance with local labelling and IAsp 1-3 times daily administered at main meals based on individual needs with or without OAD(s).
Change in FPG Baseline: Week 0	162.4 mg/dL Standard Deviation 47.8	157.8 mg/dL Standard Deviation 47.8
Change in FPG Change from baseline: Week 26	-42.1 mg/dL Standard Deviation 52.1	-40.6 mg/dL Standard Deviation 59.2
Change in FPG Change from baseline: Week 38	-48.6 mg/dL Standard Deviation 54.2	-41.5 mg/dL Standard Deviation 55.3

SECONDARY outcome

Timeframe: Week 1, week 26, week 38

Population: FAS, which included all randomised subjects. Number of subjects analyzed = number of subjects contributed to the analysis at specified time point.

Reported results are observed pre-breakfast self-measured plasma glucose (SMPG; used for titration) values at week 1 (baseline) and 26 and 38 weeks after randomisation.

Outcome measures

Measure	Insulin Degludec/Insulin Aspart n=267 Participants Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): IDegAsp OD administered at the largest meal each day with or without OAD(s). Subjects switching from pre-trial basal insulin OD or more to IDegAsp OD at trial entry were to transfer unit-to-unit. 2) Intensification period (period-2, week 26-38): IDegAsp OD/BID administered at the largest meal(s) each day (in the case of BID dosing, one meal being dinner) based on individual needs with or without OAD(s).	Insulin Glargine + Insulin Aspart n=265 Participants Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): Insulin glargine (IGlar) OD administered in accordance with local labelling and insulin aspart (IAsp) OD administered at the largest meal with or without OAD(s). Subjects switching from pre-trial basal insulin OD to IGlar OD were also to transfer unit-to-unit to IGlar, while subjects switching from basal insulin more than OD to IGlar OD were to reduce the initial total daily dose by 20% or according to local labelling. IAsp was to be initiated at 4 units with the largest meal. 2) Intensification period (period-2, week 26-38): IGlar OD administered in accordance with local labelling and IAsp 1-3 times daily administered at main meals based on individual needs with or without OAD(s).
Change in Pre-breakfast SMPG (Used for Titration) Week 1 (Baseline)	158.3 mg/dL Standard Deviation 45.7	149.4 mg/dL Standard Deviation 43.8
Change in Pre-breakfast SMPG (Used for Titration) Week 26	107.5 mg/dL Standard Deviation 24.8	103.4 mg/dL Standard Deviation 20.7
Change in Pre-breakfast SMPG (Used for Titration) Week 38	102.9 mg/dL Standard Deviation 20.0	103.8 mg/dL Standard Deviation 22.5

SECONDARY outcome

Timeframe: Week 0, week 26, week 38

Population: FAS, which included all randomised subjects. Number of subjects analyzed = number of subjects contributed to the analysis at specified time point.

Change from baseline (week 0) in postprandial SMPG increment (from 9-point profile) was evaluated 26 and 38 weeks after randomisation, respectively. 9-point SMPG profiles were measured starting in the morning 2 days prior to the scheduled visit at the time points described below: 1) Before breakfast (2 days prior to visit) 2) 90 minutes after start of the breakfast 3) Before lunch 4) 90 minutes after start of the lunch 5) Before dinner/main evening meal 6) 90 minutes after start of the dinner/main evening meal 7) At bedtime (2 days or 1 day prior to visit depending on actual clock time) 8) At 4 a.m. (1 day prior to visit) 9) Before breakfast at the following day (1 day prior to the visit).

Outcome measures

Measure	Insulin Degludec/Insulin Aspart n=267 Participants Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): IDegAsp OD administered at the largest meal each day with or without OAD(s). Subjects switching from pre-trial basal insulin OD or more to IDegAsp OD at trial entry were to transfer unit-to-unit. 2) Intensification period (period-2, week 26-38): IDegAsp OD/BID administered at the largest meal(s) each day (in the case of BID dosing, one meal being dinner) based on individual needs with or without OAD(s).	Insulin Glargine + Insulin Aspart n=265 Participants Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): Insulin glargine (IGlar) OD administered in accordance with local labelling and insulin aspart (IAsp) OD administered at the largest meal with or without OAD(s). Subjects switching from pre-trial basal insulin OD to IGlar OD were also to transfer unit-to-unit to IGlar, while subjects switching from basal insulin more than OD to IGlar OD were to reduce the initial total daily dose by 20% or according to local labelling. IAsp was to be initiated at 4 units with the largest meal. 2) Intensification period (period-2, week 26-38): IGlar OD administered in accordance with local labelling and IAsp 1-3 times daily administered at main meals based on individual needs with or without OAD(s).
Change in Postprandial SMPG Increment (From 9-point Profile) Baseline: Week 0	54.5 mg/dL Standard Deviation 37.7	48.4 mg/dL Standard Deviation 38.0
Change in Postprandial SMPG Increment (From 9-point Profile) Change from baseline: Week 26	-10.8 mg/dL Standard Deviation 46.3	-8.7 mg/dL Standard Deviation 40.6
Change in Postprandial SMPG Increment (From 9-point Profile) Change from baseline: Week 38	-17.7 mg/dL Standard Deviation 40.0	-19.7 mg/dL Standard Deviation 45.0

SECONDARY outcome

Timeframe: Weeks 0-26, weeks 16-26, weeks 0-38

Population: Safety analysis set, which included all subjects receiving at least one dose of the investigational product (IDegAsp) or comparator (IGlar). Number of subjects analyzed = number of subjects contributed to the analysis at specified time point.

Number of nocturnal, treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were analysed during the following periods: weeks 0-26, weeks 16-26 and weeks 0-38. Nocturnal hypoglycaemic episodes: episodes occurring between 00:01 and 05:59 both inclusive. Treatment emergent: hypoglycaemic episodes were defined as treatment emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product.

Outcome measures

Measure	Insulin Degludec/Insulin Aspart n=265 Participants Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): IDegAsp OD administered at the largest meal each day with or without OAD(s). Subjects switching from pre-trial basal insulin OD or more to IDegAsp OD at trial entry were to transfer unit-to-unit. 2) Intensification period (period-2, week 26-38): IDegAsp OD/BID administered at the largest meal(s) each day (in the case of BID dosing, one meal being dinner) based on individual needs with or without OAD(s).	Insulin Glargine + Insulin Aspart n=263 Participants Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): Insulin glargine (IGlar) OD administered in accordance with local labelling and insulin aspart (IAsp) OD administered at the largest meal with or without OAD(s). Subjects switching from pre-trial basal insulin OD to IGlar OD were also to transfer unit-to-unit to IGlar, while subjects switching from basal insulin more than OD to IGlar OD were to reduce the initial total daily dose by 20% or according to local labelling. IAsp was to be initiated at 4 units with the largest meal. 2) Intensification period (period-2, week 26-38): IGlar OD administered in accordance with local labelling and IAsp 1-3 times daily administered at main meals based on individual needs with or without OAD(s).
Number of Nocturnal, Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes Weeks 0-26	61 Episodes	118 Episodes
Number of Nocturnal, Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes Weeks 16-26	24 Episodes	58 Episodes
Number of Nocturnal, Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes Weeks 0-38	113 Episodes	189 Episodes

SECONDARY outcome

Timeframe: Weeks 0-26, weeks 16-26, weeks 0-38

Population: Safety analysis set, which included all subjects receiving at least one dose of the investigational product or comparator. Number of subjects analyzed = number of subjects contributed to the analysis at specified time point.

Number of treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were analysed during the following periods: weeks 0-26, weeks 16-26 and weeks 0-38. Treatment emergent: hypoglycaemic episodes were defined as treatment emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product.

Outcome measures

Measure	Insulin Degludec/Insulin Aspart n=265 Participants Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): IDegAsp OD administered at the largest meal each day with or without OAD(s). Subjects switching from pre-trial basal insulin OD or more to IDegAsp OD at trial entry were to transfer unit-to-unit. 2) Intensification period (period-2, week 26-38): IDegAsp OD/BID administered at the largest meal(s) each day (in the case of BID dosing, one meal being dinner) based on individual needs with or without OAD(s).	Insulin Glargine + Insulin Aspart n=263 Participants Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): Insulin glargine (IGlar) OD administered in accordance with local labelling and insulin aspart (IAsp) OD administered at the largest meal with or without OAD(s). Subjects switching from pre-trial basal insulin OD to IGlar OD were also to transfer unit-to-unit to IGlar, while subjects switching from basal insulin more than OD to IGlar OD were to reduce the initial total daily dose by 20% or according to local labelling. IAsp was to be initiated at 4 units with the largest meal. 2) Intensification period (period-2, week 26-38): IGlar OD administered in accordance with local labelling and IAsp 1-3 times daily administered at main meals based on individual needs with or without OAD(s).
Number of Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes Weeks 0-26	329 Episodes	376 Episodes
Number of Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes Weeks 16-26	154 Episodes	194 Episodes
Number of Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes Weeks 0-38	537 Episodes	640 Episodes

SECONDARY outcome

Timeframe: Week 26 and week 38

Population: Safety analysis set, which included all subjects receiving at least one dose of the investigational product or comparator. Number of subjects analyzed = number of subjects contributed to the analysis at specified time point.

Total insulin dose was evaluated 26 and 38 weeks after randomisation, respectively.

Outcome measures

Measure	Insulin Degludec/Insulin Aspart n=265 Participants Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): IDegAsp OD administered at the largest meal each day with or without OAD(s). Subjects switching from pre-trial basal insulin OD or more to IDegAsp OD at trial entry were to transfer unit-to-unit. 2) Intensification period (period-2, week 26-38): IDegAsp OD/BID administered at the largest meal(s) each day (in the case of BID dosing, one meal being dinner) based on individual needs with or without OAD(s).	Insulin Glargine + Insulin Aspart n=263 Participants Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): Insulin glargine (IGlar) OD administered in accordance with local labelling and insulin aspart (IAsp) OD administered at the largest meal with or without OAD(s). Subjects switching from pre-trial basal insulin OD to IGlar OD were also to transfer unit-to-unit to IGlar, while subjects switching from basal insulin more than OD to IGlar OD were to reduce the initial total daily dose by 20% or according to local labelling. IAsp was to be initiated at 4 units with the largest meal. 2) Intensification period (period-2, week 26-38): IGlar OD administered in accordance with local labelling and IAsp 1-3 times daily administered at main meals based on individual needs with or without OAD(s).
Total Insulin Dose Week 26	70.9 Units Standard Deviation 41.5	79.4 Units Standard Deviation 37.7
Total Insulin Dose Week 38	83.4 Units Standard Deviation 51.3	89.3 Units Standard Deviation 43.1

SECONDARY outcome

Timeframe: Week 0, week 26, week 38

Population: Safety analysis set, which included all subjects receiving at least one dose of the investigational product or comparator. Number of subjects analyzed = number of subjects contributed to the analysis at specified time point.

Change from baseline (week 0) in body weight was evaluated 26 and 38 weeks after randomisation, respectively.

Outcome measures

Measure	Insulin Degludec/Insulin Aspart n=265 Participants Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): IDegAsp OD administered at the largest meal each day with or without OAD(s). Subjects switching from pre-trial basal insulin OD or more to IDegAsp OD at trial entry were to transfer unit-to-unit. 2) Intensification period (period-2, week 26-38): IDegAsp OD/BID administered at the largest meal(s) each day (in the case of BID dosing, one meal being dinner) based on individual needs with or without OAD(s).	Insulin Glargine + Insulin Aspart n=263 Participants Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): Insulin glargine (IGlar) OD administered in accordance with local labelling and insulin aspart (IAsp) OD administered at the largest meal with or without OAD(s). Subjects switching from pre-trial basal insulin OD to IGlar OD were also to transfer unit-to-unit to IGlar, while subjects switching from basal insulin more than OD to IGlar OD were to reduce the initial total daily dose by 20% or according to local labelling. IAsp was to be initiated at 4 units with the largest meal. 2) Intensification period (period-2, week 26-38): IGlar OD administered in accordance with local labelling and IAsp 1-3 times daily administered at main meals based on individual needs with or without OAD(s).
Change in Body Weight Baseline: Week 0	88.5 Kg Standard Deviation 18.6	88.4 Kg Standard Deviation 17.5
Change in Body Weight Change from basline: Week 26	1.7 Kg Standard Deviation 3.2	1.4 Kg Standard Deviation 3.2
Change in Body Weight Change from basline: Week 38	2.5 Kg Standard Deviation 3.8	2.4 Kg Standard Deviation 3.2

SECONDARY outcome

Timeframe: Weeks 0-26, weeks 26-38, weeks 0-38

Population: Safety analysis set, which included all subjects receiving at least one dose of the investigational product (IDegAsp) or comparator (IGlar). Number of subjects analyzed = number of subjects contributed to the analysis at specified time point.

Number of treatment emergent adverse events (TEAEs) were analysed during the following periods: weeks 0-26, weeks 26-38 and weeks 0-38. Treatment emergent: An adverse event that had an 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. If an event had an onset date before the first day of exposure on randomised treatment and increased in severity during the treatment period, or if it had an onset date within 7 days after the last drug date, then this event was also to be considered as a TEAE.

Outcome measures

Measure	Insulin Degludec/Insulin Aspart n=265 Participants Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): IDegAsp OD administered at the largest meal each day with or without OAD(s). Subjects switching from pre-trial basal insulin OD or more to IDegAsp OD at trial entry were to transfer unit-to-unit. 2) Intensification period (period-2, week 26-38): IDegAsp OD/BID administered at the largest meal(s) each day (in the case of BID dosing, one meal being dinner) based on individual needs with or without OAD(s).	Insulin Glargine + Insulin Aspart n=263 Participants Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): Insulin glargine (IGlar) OD administered in accordance with local labelling and insulin aspart (IAsp) OD administered at the largest meal with or without OAD(s). Subjects switching from pre-trial basal insulin OD to IGlar OD were also to transfer unit-to-unit to IGlar, while subjects switching from basal insulin more than OD to IGlar OD were to reduce the initial total daily dose by 20% or according to local labelling. IAsp was to be initiated at 4 units with the largest meal. 2) Intensification period (period-2, week 26-38): IGlar OD administered in accordance with local labelling and IAsp 1-3 times daily administered at main meals based on individual needs with or without OAD(s).
Incidence of TEAEs Weeks 0-26	441 Events	408 Events
Incidence of TEAEs Weeks 26-38	173 Events	117 Events
Incidence of TEAEs Weeks 0-38	614 Events	525 Events

Adverse Events

Insulin Degludec/Insulin Aspart

Serious events: 18 serious events

Other events: 74 other events

Deaths: 0 deaths

Insulin Glargine + Insulin Aspart

Serious events: 20 serious events

Other events: 57 other events

Deaths: 2 deaths

Serious adverse events

Measure	Insulin Degludec/Insulin Aspart n=265 participants at risk Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): IDegAsp OD administered at the largest meal each day with or without OAD(s). Subjects switching from pre-trial basal insulin OD or more to IDegAsp OD at trial entry were to transfer unit-to-unit. 2) Intensification period (period-2, week 26-38): IDegAsp OD/BID administered at the largest meal(s) each day (in the case of BID dosing, one meal being dinner) based on individual needs with or without OAD(s).	Insulin Glargine + Insulin Aspart n=263 participants at risk Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): Insulin glargine (IGlar) OD administered in accordance with local labelling and insulin aspart (IAsp) OD administered at the largest meal with or without OAD(s). Subjects switching from pre-trial basal insulin OD to IGlar OD were also to transfer unit-to-unit to IGlar, while subjects switching from basal insulin more than OD to IGlar OD were to reduce the initial total daily dose by 20% or according to local labelling. IAsp was to be initiated at 4 units with the largest meal. 2) Intensification period (period-2, week 26-38): IGlar OD administered in accordance with local labelling and IAsp 1-3 times daily administered at main meals based on individual needs with or without OAD(s).
Injury, poisoning and procedural complications Accidental overdose	0.00% 0/265 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	0.38% 1/263 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Cardiac disorders Acute myocardial infarction	0.38% 1/265 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	0.38% 1/263 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma of colon	0.00% 0/265 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	0.38% 1/263 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Endocrine disorders Adrenal mass	0.00% 0/265 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	0.38% 1/263 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Infections and infestations Appendicitis	0.38% 1/265 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	0.00% 0/263 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/265 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	0.38% 1/263 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.38% 1/265 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	0.00% 0/263 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Infections and infestations Bronchitis	0.00% 0/265 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	0.38% 1/263 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Surgical and medical procedures Cholecystectomy	0.00% 0/265 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	0.38% 1/263 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Hepatobiliary disorders Cholelithiasis	0.00% 0/265 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	0.38% 1/263 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Gastrointestinal disorders Colitis	0.00% 0/265 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	0.38% 1/263 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Cardiac disorders Coronary artery disease	0.75% 2/265 • Number of events 2 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	0.38% 1/263 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Infections and infestations Epiglottitis	0.38% 1/265 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	0.00% 0/263 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Nervous system disorders Facial paralysis	0.38% 1/265 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	0.00% 0/263 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Injury, poisoning and procedural complications Fall	0.00% 0/265 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	0.38% 1/263 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Injury, poisoning and procedural complications Femoral neck fracture	0.38% 1/265 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	0.00% 0/263 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Infections and infestations Furuncle	0.38% 1/265 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	0.00% 0/263 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Gastrointestinal disorders Gastric polyps	0.00% 0/265 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	0.38% 1/263 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Hepatobiliary disorders Hepatic cirrhosis	0.00% 0/265 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	0.38% 1/263 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Surgical and medical procedures Hernia repair	0.00% 0/265 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	0.38% 1/263 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Skin and subcutaneous tissue disorders Hidradenitis	0.00% 0/265 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	0.38% 1/263 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/265 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	0.38% 1/263 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Metabolism and nutrition disorders Hypoglycaemia	0.38% 1/265 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	0.00% 0/263 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Infections and infestations Infected skin ulcer	0.38% 1/265 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	0.00% 0/263 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.38% 1/265 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	0.00% 0/263 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.38% 1/265 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	0.00% 0/263 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma in situ	0.38% 1/265 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	0.00% 0/263 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Infections and infestations Meningitis viral	0.00% 0/265 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	0.38% 1/263 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Cardiac disorders Mitral valve incompetence	0.38% 1/265 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	0.00% 0/263 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Cardiac disorders Myocardial ischaemia	0.38% 1/265 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	0.38% 1/263 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
General disorders Non-cardiac chest pain	0.00% 0/265 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	0.38% 1/263 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma metastatic	0.00% 0/265 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	0.76% 2/263 • Number of events 2 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Gastrointestinal disorders Pancreatitis	0.38% 1/265 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	0.00% 0/263 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Infections and infestations Peritonitis	0.38% 1/265 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	0.00% 0/263 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Infections and infestations Peritonsillar abscess	0.38% 1/265 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	0.00% 0/263 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pituitary tumour benign	0.38% 1/265 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	0.00% 0/263 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Infections and infestations Pneumonia	0.38% 1/265 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	0.38% 1/263 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Infections and infestations Respiratory tract infection viral	0.38% 1/265 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	0.00% 0/263 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.38% 1/265 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	0.00% 0/263 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Renal and urinary disorders Tubulointerstitial nephritis	0.38% 1/265 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	0.00% 0/263 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Renal and urinary disorders Ureterolithiasis	0.00% 0/265 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	0.38% 1/263 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Nervous system disorders VIth nerve paralysis	0.00% 0/265 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	0.38% 1/263 • Number of events 1 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Ear and labyrinth disorders Vertigo	0.00% 0/265 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	0.76% 2/263 • Number of events 2 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.

Other adverse events

Measure	Insulin Degludec/Insulin Aspart n=265 participants at risk Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): IDegAsp OD administered at the largest meal each day with or without OAD(s). Subjects switching from pre-trial basal insulin OD or more to IDegAsp OD at trial entry were to transfer unit-to-unit. 2) Intensification period (period-2, week 26-38): IDegAsp OD/BID administered at the largest meal(s) each day (in the case of BID dosing, one meal being dinner) based on individual needs with or without OAD(s).	Insulin Glargine + Insulin Aspart n=263 participants at risk Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): Insulin glargine (IGlar) OD administered in accordance with local labelling and insulin aspart (IAsp) OD administered at the largest meal with or without OAD(s). Subjects switching from pre-trial basal insulin OD to IGlar OD were also to transfer unit-to-unit to IGlar, while subjects switching from basal insulin more than OD to IGlar OD were to reduce the initial total daily dose by 20% or according to local labelling. IAsp was to be initiated at 4 units with the largest meal. 2) Intensification period (period-2, week 26-38): IGlar OD administered in accordance with local labelling and IAsp 1-3 times daily administered at main meals based on individual needs with or without OAD(s).
Musculoskeletal and connective tissue disorders Back pain	6.0% 16/265 • Number of events 17 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	3.4% 9/263 • Number of events 9 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Nervous system disorders Headache	10.2% 27/265 • Number of events 52 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	6.1% 16/263 • Number of events 23 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Infections and infestations Nasopharyngitis	13.6% 36/265 • Number of events 49 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	8.4% 22/263 • Number of events 27 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.
Infections and infestations Upper respiratory tract infection	5.7% 15/265 • Number of events 17 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.	6.5% 17/263 • Number of events 17 • Week 0 to week 38 (treatment period) + 7 days (follow-up period). All presented adverse events are treatment emergent (i.e., TEAEs). Results are based on the safety analysis set, which included all subjects receiving at least one dose of the investigational product.

Additional Information

Clinical Reporting Anchor and Disclosure (1452)

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