Trial Outcomes & Findings for A Trial Comparing the Efficacy and Safety of Insulin Degludec/Liraglutide, Insulin Degludec and Liraglutide in Japanese Subjects With Type 2 Diabetes Mellitus. (NCT NCT02607306)

Results Overview

Change from baseline (week 0) in HbA1c after 52 weeks of treatment was measured. Statistical analyses were performed to test the hypotheses: non-inferiority of IDegLira vs. IDeg and superiority of IDegLira vs. Liraglutide (Lira).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

819 participants

Primary outcome timeframe

Week 0, Week 52

Results posted on

2021-04-09

Participant Flow

The trial was conducted at 71 sites in Japan. 71 sites screened and randomised subjects.

Participant milestones

Participant milestones
Measure	Insulin Degludec/Liraglutide Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.
Overall Study STARTED	275	271	273
Overall Study COMPLETED	254	248	263
Overall Study NOT COMPLETED	21	23	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Insulin Degludec/Liraglutide Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.
Overall Study Adverse Event	8	6	6
Overall Study Unclassified	1	4	0
Overall Study Withdrawal by Subject	8	10	2
Overall Study Lack of Efficacy	0	1	1
Overall Study Protocol Violation	4	2	1

Baseline Characteristics

A Trial Comparing the Efficacy and Safety of Insulin Degludec/Liraglutide, Insulin Degludec and Liraglutide in Japanese Subjects With Type 2 Diabetes Mellitus.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Insulin Degludec/Liraglutide n=275 Participants Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec n=271 Participants Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide n=273 Participants Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Total n=819 Participants Total of all reporting groups
Age, Continuous	56.9 Years STANDARD_DEVIATION 10.2 • n=5 Participants	57.8 Years STANDARD_DEVIATION 9.9 • n=7 Participants	56.8 Years STANDARD_DEVIATION 10.1 • n=5 Participants	57.2 Years STANDARD_DEVIATION 10.1 • n=4 Participants
Sex: Female, Male Female	81 Participants n=5 Participants	76 Participants n=7 Participants	81 Participants n=5 Participants	238 Participants n=4 Participants
Sex: Female, Male Male	194 Participants n=5 Participants	195 Participants n=7 Participants	192 Participants n=5 Participants	581 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	275 Participants n=5 Participants	271 Participants n=7 Participants	273 Participants n=5 Participants	819 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	275 Participants n=5 Participants	271 Participants n=7 Participants	273 Participants n=5 Participants	819 Participants n=4 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	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Glycosylated Haemoglobin (HbA1c)	8.52 Percentage of HbA1c STANDARD_DEVIATION 1.12 • n=5 Participants	8.53 Percentage of HbA1c STANDARD_DEVIATION 1.05 • n=7 Participants	8.32 Percentage of HbA1c STANDARD_DEVIATION 0.99 • n=5 Participants	8.45 Percentage of HbA1c STANDARD_DEVIATION 1.06 • n=4 Participants

PRIMARY outcome

Timeframe: Week 0, Week 52

Population: Full Analysis Set (FAS) included all randomised subjects (819 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method.

Change from baseline (week 0) in HbA1c after 52 weeks of treatment was measured. Statistical analyses were performed to test the hypotheses: non-inferiority of IDegLira vs. IDeg and superiority of IDegLira vs. Liraglutide (Lira).

Outcome measures

Outcome measures
Measure	Insulin Degludec/Liraglutide n=275 Participants Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec n=271 Participants Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide n=273 Participants Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.
Change From Baseline in HbA1c (Glycosylated Haemoglobin) Tested for Non-inferiority of IDegLira vs IDeg and Superiority of IDegLira vs Lira	-2.42 Percentage of HbA1c Standard Deviation 1.04	-1.80 Percentage of HbA1c Standard Deviation 1.02	-1.80 Percentage of HbA1c Standard Deviation 0.92

SECONDARY outcome

Timeframe: Week 0, Week 52

Population: Full Analysis Set (FAS) included all randomised subjects (819 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method.

Change from baseline (week 0) in body weight after 52 weeks of treatment.

Outcome measures

Outcome measures
Measure	Insulin Degludec/Liraglutide n=275 Participants Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec n=271 Participants Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide n=273 Participants Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.
Change From Baseline in Body Weight (kg)	2.9 Kg Standard Deviation 3.2	4.1 Kg Standard Deviation 4.3	-1.0 Kg Standard Deviation 3.4

SECONDARY outcome

Timeframe: Weeks 0-52

Population: Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparator (819 subjects). Subjects in the safety set contributed to the evaluation "as treated".

Treatment emergent hypoglycaemic episode is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Severe or BG confirmed hypoglycaemic episodes were defined as episodes that were 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 or without symptoms consistent with hypoglycaemia. Severe hypoglycaemia according to the ADA definition: 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

Outcome measures
Measure	Insulin Degludec/Liraglutide n=275 Participants Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec n=271 Participants Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide n=273 Participants Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.
Number of Treatment Emergent Severe or Blood Glucose (BG) Confirmed Hypoglycaemic Episodes	467 Episodes	869 Episodes	13 Episodes

SECONDARY outcome

Timeframe: Week 0, Week 52

Population: Full Analysis Set (FAS) included all randomised subjects (819 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method.

Change from baseline (week 0) in HbA1c after 52 weeks of treatment was measured. Statistical analysis was performed to test the hypothesis: superiority of IDegLira vs. IDeg.

Outcome measures

Outcome measures
Measure	Insulin Degludec/Liraglutide n=275 Participants Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec n=271 Participants Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide n=273 Participants Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.
Change From Baseline in HbA1c (Glycosylated Haemoglobin) Tested for Superiority of IDegLira vs IDeg	-2.42 Percentage of HbA1c Standard Deviation 1.04	-1.80 Percentage of HbA1c Standard Deviation 1.02	-1.80 Percentage of HbA1c Standard Deviation 0.92

SECONDARY outcome

Timeframe: Week 0, Week 52

Population: Full Analysis Set (FAS) included all randomised subjects (819 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method. Number Analyzed = subjects with available data.

Change from baseline (week 0) in FPG after 52 weeks

Outcome measures

Outcome measures
Measure	Insulin Degludec/Liraglutide n=275 Participants Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec n=271 Participants Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide n=272 Participants Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.
Change From Baseline in Fasting Plasma Glucose (FPG)	-4.08 mmol/L Standard Deviation 2.47	-3.97 mmol/L Standard Deviation 2.56	-2.62 mmol/L Standard Deviation 1.95

SECONDARY outcome

Timeframe: After 52 weeks of treatment

Population: Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparator (819 subjects). Subjects in the safety set contributed to the evaluation "as treated". Missing data were imputed using LOCF method. This endpoint evaluation is only applicable for subjects in IDegLira and IDeg arm.

Actual daily total insulin dose after 52 weeks of treatment.

Outcome measures

Outcome measures
Measure	Insulin Degludec/Liraglutide n=275 Participants Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec n=271 Participants Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.
Insulin Dose	27.7 Insulin Units/Day Standard Deviation 14.8	34.8 Insulin Units/Day Standard Deviation 26.0	—

SECONDARY outcome

Timeframe: After 52 weeks of treatment

Population: Full Analysis Set (FAS) included all randomised subjects (819 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method.

Number of subjects with HbA1c less than 7.0% after 52 weeks of treatment.

Outcome measures

Outcome measures
Measure	Insulin Degludec/Liraglutide n=275 Participants Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec n=271 Participants Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide n=273 Participants Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.
Responder (Yes/no): HbA1c Less Than 7.0% Yes	245 Participants	189 Participants	208 Participants
Responder (Yes/no): HbA1c Less Than 7.0% No	30 Participants	82 Participants	65 Participants

SECONDARY outcome

Timeframe: After 52 weeks of treatment

Population: Full Analysis Set (FAS) included all randomised subjects (819 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method.

Number of subjects with HbA1c less than 7.0% and without weight gain after 52 weeks of treatment.

Outcome measures

Outcome measures
Measure	Insulin Degludec/Liraglutide n=275 Participants Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec n=271 Participants Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide n=273 Participants Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.
Responder (Yes/no): HbA1c Less Than 7.0% and Change in Body Weight From Baseline Below or Equal to Zero Yes	44 Participants	22 Participants	142 Participants
Responder (Yes/no): HbA1c Less Than 7.0% and Change in Body Weight From Baseline Below or Equal to Zero No	231 Participants	249 Participants	131 Participants

SECONDARY outcome

Timeframe: After 52 weeks of treatment

Population: Full Analysis Set (FAS) included all randomised subjects (819 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method. Number Analyzed = subjects with available data.

Number of subjects with HbA1c less than 7.0% after 52 weeks, who did not experience treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes during the last 12 weeks of treatment. Treatment emergent hypoglycaemic episode is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Severe or BG confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification or BG confirmed by a plasma glucose value \< 3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.

Outcome measures

Outcome measures
Measure	Insulin Degludec/Liraglutide n=270 Participants Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec n=265 Participants Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide n=271 Participants Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.
Responder (Yes/no): HbA1c Less Than 7.0% Without Treatment Emergent Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemic Episodes During the Last 12 Weeks of Treatment. Yes	227 Participants	169 Participants	206 Participants
Responder (Yes/no): HbA1c Less Than 7.0% Without Treatment Emergent Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemic Episodes During the Last 12 Weeks of Treatment. No	43 Participants	96 Participants	65 Participants

SECONDARY outcome

Timeframe: After 52 weeks of treatment

Population: Full Analysis Set (FAS) included all randomised subjects (819 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method. Number Analyzed = subjects with available data.

Number of subjects with HbA1c less than 7.0% and without weight gain, who did not experience treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes during the last 12 weeks of treatment. Treatment emergent hypoglycaemic episode is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Severe or BG confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification or BG confirmed by a plasma glucose value \< 3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.

Outcome measures

Outcome measures
Measure	Insulin Degludec/Liraglutide n=270 Participants Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec n=265 Participants Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide n=271 Participants Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.
Responder (Yes/no): HbA1c Less Than 7.0% and Change in Body Weight From Baseline Below or Equal to Zero and Without Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During the Last 12 Weeks of Treatment Yes	37 Participants	22 Participants	141 Participants
Responder (Yes/no): HbA1c Less Than 7.0% and Change in Body Weight From Baseline Below or Equal to Zero and Without Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During the Last 12 Weeks of Treatment No	233 Participants	243 Participants	130 Participants

SECONDARY outcome

Timeframe: After 52 weeks of treatment

Population: Full Analysis Set (FAS) included all randomised subjects (819 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method.

Number of subjects with HbA1c less than 6.5% after 52 weeks of treatment.

Outcome measures

Outcome measures
Measure	Insulin Degludec/Liraglutide n=275 Participants Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec n=271 Participants Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide n=273 Participants Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.
Responder (Yes/no): HbA1c Less Than 6.5% Yes	213 Participants	134 Participants	171 Participants
Responder (Yes/no): HbA1c Less Than 6.5% No	62 Participants	137 Participants	102 Participants

SECONDARY outcome

Timeframe: After 52 weeks of treatment

Population: Full Analysis Set (FAS) included all randomised subjects (819 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method.

Number of subjects with HbA1c less than 6.5% and without weight gain after 52 weeks of treatment.

Outcome measures

Outcome measures
Measure	Insulin Degludec/Liraglutide n=275 Participants Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec n=271 Participants Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide n=273 Participants Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.
Responder (Yes/no): HbA1c Less Than 6.5% and Change in Body Weight From Baseline Below or Equal to Zero Yes	41 Participants	17 Participants	126 Participants
Responder (Yes/no): HbA1c Less Than 6.5% and Change in Body Weight From Baseline Below or Equal to Zero No	234 Participants	254 Participants	147 Participants

SECONDARY outcome

Timeframe: After 52 weeks of treatment

Population: Full Analysis Set (FAS) included all randomised subjects (819 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method. Number Analyzed = subjects with available data.

Number of subjects with HbA1c less than 6.5% after 52 weeks, who did not experience treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes during the last 12 weeks of treatment. Treatment emergent hypoglycaemic episode is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Severe or BG confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification or BG confirmed by a plasma glucose value \< 3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.

Outcome measures

Outcome measures
Measure	Insulin Degludec/Liraglutide n=270 Participants Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec n=265 Participants Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide n=271 Participants Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.
Responder (Yes/no): HbA1c Less Than 6.5% Without Treatment Emergent Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemic Episodes During the Last 12 Weeks of Treatment. No	72 Participants	142 Participants	101 Participants
Responder (Yes/no): HbA1c Less Than 6.5% Without Treatment Emergent Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemic Episodes During the Last 12 Weeks of Treatment. Yes	198 Participants	123 Participants	170 Participants

SECONDARY outcome

Timeframe: After 52 weeks of treatment

Population: Full Analysis Set (FAS) included all randomised subjects (819 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method. Number Analyzed = subjects with available data.

Number of subjects with HbA1c less than 6.5% with no weight gain, who did not experience treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes during the last 12 weeks of treatment. Treatment emergent hypoglycaemic episode is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Severe or BG confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification or BG confirmed by a plasma glucose value \< 3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.

Outcome measures

Outcome measures
Measure	Insulin Degludec/Liraglutide n=270 Participants Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec n=265 Participants Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide n=271 Participants Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.
Responder (Yes/no): HbA1c Less Than 6.5% and Change in Body Weight From Baseline Below or Equal to Zero and Without Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During the Last 12 Weeks of Treatment Yes	35 Participants	17 Participants	125 Participants
Responder (Yes/no): HbA1c Less Than 6.5% and Change in Body Weight From Baseline Below or Equal to Zero and Without Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During the Last 12 Weeks of Treatment No	235 Participants	248 Participants	146 Participants

SECONDARY outcome

Timeframe: Week 0, Week 52

Population: Full Analysis Set (FAS) included all randomised subjects (819 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method.

Change from baseline (week 0) in waist circumference after 52 weeks of treatment.

Outcome measures

Outcome measures
Measure	Insulin Degludec/Liraglutide n=275 Participants Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec n=271 Participants Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide n=273 Participants Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.
Change in Waist Circumference	2.5 Cm Standard Deviation 4.5	3.4 Cm Standard Deviation 5.2	-1.1 Cm Standard Deviation 4.4

SECONDARY outcome

Timeframe: Week 0, Week 52

Population: Full Analysis Set (FAS) included all randomised subjects (819 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method.

Change from baseline in blood pressure (systolic and diastolic) after 52 weeks of treatment.

Outcome measures

Outcome measures
Measure	Insulin Degludec/Liraglutide n=275 Participants Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec n=271 Participants Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide n=273 Participants Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.
Change in Blood Pressure (Systolic and Diastolic) Systolic blood pressure	1.7 mmHg Standard Deviation 12.0	3.4 mmHg Standard Deviation 14.3	-1.8 mmHg Standard Deviation 13.0
Change in Blood Pressure (Systolic and Diastolic) Diastolic blood pressure	0.5 mmHg Standard Deviation 7.9	0.6 mmHg Standard Deviation 9.3	-0.4 mmHg Standard Deviation 8.3

SECONDARY outcome

Timeframe: After 52 weeks of the treatment

Population: Full Analysis Set (FAS) included all randomised subjects (819 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method. Number Analyzed = subjects with available data.

Subjects were instructed to measure their plasma glucose at following timepoints: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner, at bedtime, at 4:00 a.m. and before breakfast the following day.

Outcome measures

Outcome measures
Measure	Insulin Degludec/Liraglutide n=275 Participants Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec n=271 Participants Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide n=273 Participants Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.
Self-Measured Blood Glucose (SMBG) 9-point Profile: 9-point Profile (Individual Points in the Profile) Before breakfast	5.90 mmol/L Standard Deviation 1.45	5.93 mmol/L Standard Deviation 1.64	7.35 mmol/L Standard Deviation 1.70
Self-Measured Blood Glucose (SMBG) 9-point Profile: 9-point Profile (Individual Points in the Profile) 90 minutes after start of breakfast	9.57 mmol/L Standard Deviation 2.83	10.43 mmol/L Standard Deviation 3.16	10.59 mmol/L Standard Deviation 3.25
Self-Measured Blood Glucose (SMBG) 9-point Profile: 9-point Profile (Individual Points in the Profile) Before lunch	6.01 mmol/L Standard Deviation 1.90	6.72 mmol/L Standard Deviation 2.59	6.87 mmol/L Standard Deviation 2.07
Self-Measured Blood Glucose (SMBG) 9-point Profile: 9-point Profile (Individual Points in the Profile) 90 minutes after start of lunch	9.85 mmol/L Standard Deviation 3.16	11.12 mmol/L Standard Deviation 3.04	10.59 mmol/L Standard Deviation 3.38
Self-Measured Blood Glucose (SMBG) 9-point Profile: 9-point Profile (Individual Points in the Profile) Before dinner	6.47 mmol/L Standard Deviation 2.44	6.90 mmol/L Standard Deviation 2.57	7.03 mmol/L Standard Deviation 2.04
Self-Measured Blood Glucose (SMBG) 9-point Profile: 9-point Profile (Individual Points in the Profile) 90 minutes after start of dinner	9.67 mmol/L Standard Deviation 3.01	10.89 mmol/L Standard Deviation 3.25	10.14 mmol/L Standard Deviation 3.03
Self-Measured Blood Glucose (SMBG) 9-point Profile: 9-point Profile (Individual Points in the Profile) Bedtime	8.27 mmol/L Standard Deviation 2.79	9.49 mmol/L Standard Deviation 3.28	8.73 mmol/L Standard Deviation 2.58
Self-Measured Blood Glucose (SMBG) 9-point Profile: 9-point Profile (Individual Points in the Profile) At 4:00 a.m.	6.12 mmol/L Standard Deviation 1.70	6.41 mmol/L Standard Deviation 2.18	7.27 mmol/L Standard Deviation 1.79
Self-Measured Blood Glucose (SMBG) 9-point Profile: 9-point Profile (Individual Points in the Profile) Before breakfast the following day	5.77 mmol/L Standard Deviation 1.56	5.71 mmol/L Standard Deviation 1.68	7.13 mmol/L Standard Deviation 1.68

SECONDARY outcome

Timeframe: Week 0, week 52

Population: Full Analysis Set (FAS) included all randomised subjects (819 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method. Number Analyzed = subjects with available data.

Subjects were instructed to measure their plasma glucose at following timepoints: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner, at bedtime, at 4:00 a.m. and before breakfast the following day. Mean of the 9-point profile was defined as the area under the profile (calculated using the trapezoidal method) divided by the measurement time.

Outcome measures

Outcome measures
Measure	Insulin Degludec/Liraglutide n=275 Participants Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec n=269 Participants Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide n=272 Participants Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.
Change in SMBG 9-point Profile - Mean of the 9-point Profile	-4.60 mmol/L Standard Deviation 2.65	-3.84 mmol/L Standard Deviation 2.63	-3.46 mmol/L Standard Deviation 2.37

SECONDARY outcome

Timeframe: Week 0, week 52

Population: Full Analysis Set (FAS) included all randomised subjects (819 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method. Number Analyzed = subjects with available data.

Subjects were instructed to measure their plasma glucose at following timepoints: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner, at bedtime, at 4:00 a.m. and before breakfast the following day. The mean increment over all meals was derived as the mean of all available meal increments.

Outcome measures

Outcome measures
Measure	Insulin Degludec/Liraglutide n=275 Participants Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec n=269 Participants Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide n=272 Participants Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.
Change in SMBG 9-point Profile - Mean of Postprandial Increments (From Before Meal to 90 Min After for Breakfast, Lunch and Dinner)	-0.74 mmol/L Standard Deviation 2.51	-0.27 mmol/L Standard Deviation 2.39	-1.01 mmol/L Standard Deviation 2.38

SECONDARY outcome

Timeframe: After 52 weeks of treatment

Population: Full Analysis Set (FAS) included all randomised subjects (819 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method.

Total cholesterol after 52 weeks of treatment was represented as ratio to baseline (week 0) values.

Outcome measures

Outcome measures
Measure	Insulin Degludec/Liraglutide n=275 Participants Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec n=271 Participants Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide n=273 Participants Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.
Total Cholesterol as a Ratio to Baseline at 52 Weeks	0.92 Ratio Geometric Coefficient of Variation 13.9	0.97 Ratio Geometric Coefficient of Variation 11.9	0.94 Ratio Geometric Coefficient of Variation 13.0

SECONDARY outcome

Timeframe: After 52 weeks of treatment

Population: Full Analysis Set (FAS) included all randomised subjects (819 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method.

Low density lipoprotein (LDL) cholesterol after 52 weeks of treatment was represented as ratio to baseline (week 0) values.

Outcome measures

Outcome measures
Measure	Insulin Degludec/Liraglutide n=275 Participants Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec n=271 Participants Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide n=273 Participants Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.
Low Density Lipoprotein (LDL) Cholesterol as a Ratio to Baseline at 52 Weeks	0.91 Ratio Geometric Coefficient of Variation 23.4	0.99 Ratio Geometric Coefficient of Variation 18.2	0.93 Ratio Geometric Coefficient of Variation 24.2

SECONDARY outcome

Timeframe: After 52 weeks of treatment

Population: Full Analysis Set (FAS) included all randomised subjects (819 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method.

High density lipoprotein (HDL) cholesterol after 52 weeks of treatment was represented as ratio to baseline (week 0) values.

Outcome measures

Outcome measures
Measure	Insulin Degludec/Liraglutide n=275 Participants Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec n=271 Participants Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide n=273 Participants Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.
High Density Lipoprotein (HDL) Cholesterol as a Ratio to Baseline at 52 Weeks	0.94 Ratio Geometric Coefficient of Variation 16.4	0.94 Ratio Geometric Coefficient of Variation 14.6	0.99 Ratio Geometric Coefficient of Variation 14.5

SECONDARY outcome

Timeframe: After 52 weeks of treatment

Population: Full Analysis Set (FAS) included all randomised subjects (819 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method.

Very low density lipoprotein (VLDL) cholesterol after 52 weeks of treatment was represented as ratio to baseline (week 0) values.

Outcome measures

Outcome measures
Measure	Insulin Degludec/Liraglutide n=275 Participants Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec n=271 Participants Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide n=273 Participants Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.
Very Low Density Lipoprotein (VLDL) Cholesterol as a Ratio to Baseline at 52 Weeks	0.92 Ratio Geometric Coefficient of Variation 44.3	0.97 Ratio Geometric Coefficient of Variation 42.1	0.91 Ratio Geometric Coefficient of Variation 42.2

SECONDARY outcome

Timeframe: After 52 weeks of treatment

Population: Full Analysis Set (FAS) included all randomised subjects (819 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method.

Triglycerides after 52 weeks of treatment was represented as ratio to baseline (week 0) values.

Outcome measures

Outcome measures
Measure	Insulin Degludec/Liraglutide n=275 Participants Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec n=271 Participants Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide n=273 Participants Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.
Triglycerides as a Ratio to Baseline at 52 Weeks	0.91 Ratio Geometric Coefficient of Variation 48.3	0.96 Ratio Geometric Coefficient of Variation 44.2	0.91 Ratio Geometric Coefficient of Variation 44.0

SECONDARY outcome

Timeframe: After 52 weeks of treatment

Population: Full Analysis Set (FAS) included all randomised subjects (819 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method.

Free fatty acids after 52 weeks of treatment was represented as ratio to baseline (week 0) values.

Outcome measures

Outcome measures
Measure	Insulin Degludec/Liraglutide n=275 Participants Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec n=271 Participants Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide n=273 Participants Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.
Free Fatty Acids as a Ratio to Baseline at 52 Weeks	0.74 Ratio Geometric Coefficient of Variation 60.8	0.70 Ratio Geometric Coefficient of Variation 59.3	0.93 Ratio Geometric Coefficient of Variation 49.5

SECONDARY outcome

Timeframe: After 52 weeks of treatment

Population: Full Analysis Set (FAS) included all randomised subjects (819 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method. Number Analyzed = subjects with available data.

Fasting C-peptide after 52 weeks of treatment was represented as ratio to baseline (week 0) values.

Outcome measures

Outcome measures
Measure	Insulin Degludec/Liraglutide n=275 Participants Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec n=271 Participants Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide n=272 Participants Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.
Fasting C-peptide as a Ratio to Baseline at 52 Weeks	0.61 Ratio Geometric Coefficient of Variation 75.6	0.42 Ratio Geometric Coefficient of Variation 82.6	1.12 Ratio Geometric Coefficient of Variation 29.9

SECONDARY outcome

Timeframe: After 52 weeks of treatment

Population: Full Analysis Set (FAS) included all randomised subjects (819 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method.

Fasting human insulin after 52 weeks of treatment was represented as ratio to baseline (week 0) values.

Outcome measures

Outcome measures
Measure	Insulin Degludec/Liraglutide n=275 Participants Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec n=271 Participants Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide n=273 Participants Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.
Fasting Human Insulin as a Ratio to Baseline at 52 Weeks	0.90 Ratio Geometric Coefficient of Variation 89.0	0.61 Ratio Geometric Coefficient of Variation 81.1	1.52 Ratio Geometric Coefficient of Variation 66.6

SECONDARY outcome

Timeframe: After 52 weeks of treatment

Population: Full Analysis Set (FAS) included all randomised subjects (819 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method. Number Analyzed = subjects with available data.

Fasting glucagon after 52 weeks of treatment was represented as ratio to baseline (week 0) values.

Outcome measures

Outcome measures
Measure	Insulin Degludec/Liraglutide n=275 Participants Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec n=271 Participants Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide n=272 Participants Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.
Fasting Glucagon as a Ratio to Baseline at 52 Weeks	0.95 Ratio Geometric Coefficient of Variation 27.9	0.94 Ratio Geometric Coefficient of Variation 27.6	0.96 Ratio Geometric Coefficient of Variation 25.7

SECONDARY outcome

Timeframe: After 52 weeks of treatment

Population: Full Analysis Set (FAS) included all randomised subjects (819 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method. Number Analyzed = subjects with available data.

Proinsulin after 52 weeks of treatment was represented as ratio to baseline (week 0) values.

Outcome measures

Outcome measures
Measure	Insulin Degludec/Liraglutide n=270 Participants Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec n=266 Participants Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide n=264 Participants Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.
Proinsulin as a Ratio to Baseline at 52 Weeks	0.18 Ratio Geometric Coefficient of Variation 231.5	0.17 Ratio Geometric Coefficient of Variation 188.8	0.59 Ratio Geometric Coefficient of Variation 85.9

SECONDARY outcome

Timeframe: 0-52 weeks

Population: Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparator (819 subjects). Subjects in the safety set contributed to the evaluation "as treated".

Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. If the event had onset date before the first day of exposure on randomised treatment and increased in severity during the treatment period and until 7 days after the last drug date, then this event was considered as a TEAE.

Outcome measures

Outcome measures
Measure	Insulin Degludec/Liraglutide n=275 Participants Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec n=271 Participants Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide n=273 Participants Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.
Number of Treatment Emergent Adverse Events (TEAEs)	873 Events	829 Events	885 Events

SECONDARY outcome

Timeframe: 0-52 weeks

Population: Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparator (819 subjects). Subjects in the safety set contributed to the evaluation "as treated".

Treatment emergent hypoglycaemic episode is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Severe or BG confirmed symptomatic hypoglycaemic episodes were defined as episodes that were 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 according to the ADA definition: 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

Outcome measures
Measure	Insulin Degludec/Liraglutide n=275 Participants Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec n=271 Participants Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide n=273 Participants Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.
Number of Treatment Emergent Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemic Episodes	135 Episodes	362 Episodes	136 Episodes

SECONDARY outcome

Timeframe: 0-52 weeks

Population: Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparator (819 subjects). Subjects in the safety set contributed to the evaluation "as treated".

Treatment emergent hypoglycaemic episode is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Nocturnal period: The period between 00:01 and 05:59 a.m. (both inclusive). Severe or BG confirmed symptomatic hypoglycaemic episodes were defined as episodes that were 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 according to the ADA definition: 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

Outcome measures
Measure	Insulin Degludec/Liraglutide n=275 Participants Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec n=271 Participants Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide n=273 Participants Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.
Number of Treatment Emergent Nocturnal Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes	16 Episodes	42 Episodes	0 Episodes

SECONDARY outcome

Timeframe: 0-52 weeks

Population: Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparator (819 subjects). Subjects in the safety set contributed to the evaluation "as treated".

Results represent total number of treatment emergent hypoglycaemic episodes that fall under ADA's definition of hypoglycaemia. ADA's definition of hypoglycaemia includes following categories: 1. Severe hypoglycaemia 2. Documented symptomatic hypoglycaemia 3. Asymptomatic hypoglycaemia 4. Probable symptomatic hypoglycaemia 5. Pseudo-hypoglycaemia. Treatment emergent hypoglycaemic episode is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.

Outcome measures

Outcome measures
Measure	Insulin Degludec/Liraglutide n=275 Participants Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec n=271 Participants Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide n=273 Participants Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.
Number of Treatment Emergent Hypoglycaemic Episodes According to American Diabetes Association (ADA) Definition	4830 Episodes	6340 Episodes	162 Episodes

SECONDARY outcome

Timeframe: at week 52

Population: Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparator (819 subjects). Subjects in the safety set contributed to the evaluation "as treated". Missing data were imputed using LOCF method. This endpoint is only applicable for subjects in IDegLira and IDeg arm.

Insulin degludec (IDeg)-specific antibodies were measured at week 52, as %B/T (percentage of bound \& precipitated radioactive drug/total added drug to the sample). A sample is measured in 2 different series. In series 1, the radioactive IDeg (tracer) and surplus unlabeled IDeg are added to the sample. In series 2, the tracer and surplus unlabeled human insulin are added to the sample. Series 1 represents unspecific background binding. Series 2 represents IDeg specific antibodies including unspecific background binding. The reported %B/T is calculated by subtracting the background %B/T in series 1 from the %B/T result in series 2. If the background result has higher values than the %B/T in series 2, the resulting value is negative %B/T. Here, a negative %B/T value means that the test samples do not have IDeg-specific antibodies. The reason for getting a negative value for %B/T is due to variation in the analytical background. Thus, the results presented are not a change from baseline.

Outcome measures

Outcome measures
Measure	Insulin Degludec/Liraglutide n=275 Participants Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec n=271 Participants Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.
Anti-drug Antibodies: Anti-insulin Degludec Antibodies	0.12 Percentage B/T Standard Deviation 3.34	-0.11 Percentage B/T Standard Deviation 0.42	—

SECONDARY outcome

Timeframe: at week 52

Population: Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparator (819 subjects). Subjects in the safety set contributed to the evaluation "as treated". Missing data were imputed using LOCF method.This endpoint is only applicable for subjects in IDegLira and Lira arm.

Anti-liraglutide antibodies were measured at week 52. Number of participants positive or negative for anti-liraglutide antibodies at week 52 were reported.

Outcome measures

Outcome measures
Measure	Insulin Degludec/Liraglutide n=275 Participants Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec n=273 Participants Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.
Anti-drug Antibodies: Number of Participants Positive or Negative for Anti-liraglutide Antibodies Negative	247 Participants	224 Participants	—
Anti-drug Antibodies: Number of Participants Positive or Negative for Anti-liraglutide Antibodies Positive	28 Participants	49 Participants	—

SECONDARY outcome

Timeframe: at screening (week -2 to week 0), at week 52

Population: Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparator (819 subjects). Subjects in the safety set contributed to the evaluation "as treated". Number Analyzed = subjects with available data.

The result of the fundus photography/dilated fundoscopy was interpreted by the investigator into following categories: Normal; Abnormal (Abn), Not Clinically significant (NCS); Abnormal, Clinically significant (CS). Reported results are number of subjects with 'normal'; 'Abn, NCS' and 'Abn, CS' fundoscopy/fundus photography results at screening (week -2 to week 0) and week 52.

Outcome measures

Outcome measures
Measure	Insulin Degludec/Liraglutide n=275 Participants Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec n=271 Participants Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide n=273 Participants Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.
Change in Clinical Evaluation: Fundoscopy or Fundus Photography Left eye - at screening visit - normal	225 Participants	213 Participants	211 Participants
Change in Clinical Evaluation: Fundoscopy or Fundus Photography Left eye - at screening visit - Abn, NCS	10 Participants	16 Participants	14 Participants
Change in Clinical Evaluation: Fundoscopy or Fundus Photography Left eye - at screening visit - Abn, CS	39 Participants	42 Participants	47 Participants
Change in Clinical Evaluation: Fundoscopy or Fundus Photography Left eye - week 52 - normal	217 Participants	214 Participants	212 Participants
Change in Clinical Evaluation: Fundoscopy or Fundus Photography Left eye - week 52 - Abn, NCS	17 Participants	16 Participants	15 Participants
Change in Clinical Evaluation: Fundoscopy or Fundus Photography Left eye - week 52 - Abn, CS	40 Participants	41 Participants	45 Participants
Change in Clinical Evaluation: Fundoscopy or Fundus Photography Right eye - at screening visit - normal	224 Participants	212 Participants	207 Participants
Change in Clinical Evaluation: Fundoscopy or Fundus Photography Right eye - at screening visit - Abn, NCS	10 Participants	14 Participants	12 Participants
Change in Clinical Evaluation: Fundoscopy or Fundus Photography Right eye - at screening visit - Abn, CS	41 Participants	45 Participants	54 Participants
Change in Clinical Evaluation: Fundoscopy or Fundus Photography Right eye - week 52 - normal	220 Participants	217 Participants	209 Participants
Change in Clinical Evaluation: Fundoscopy or Fundus Photography Right eye - week 52 - Abn, NCS	14 Participants	14 Participants	15 Participants
Change in Clinical Evaluation: Fundoscopy or Fundus Photography Right eye - week 52 - Abn, CS	41 Participants	40 Participants	49 Participants

SECONDARY outcome

Timeframe: at screening (week -2 to week 0), at week 52

Population: Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparator (819 subjects). Subjects in the safety set contributed to the evaluation "as treated".

The result of the ECG was interpreted by the investigator into following categories: Normal; Abnormal (Abn), Not Clinically significant (NCS); Abnormal, Clinically significant (CS). Reported results are number of subjects with 'normal'; 'Abn, NCS' and 'Abn, CS' ECG results at screening (week -2 to week 0) and week 52.

Outcome measures

Outcome measures
Measure	Insulin Degludec/Liraglutide n=275 Participants Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec n=271 Participants Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide n=273 Participants Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.
Change in Clinical Evaluation: Electrocardiogram (ECG) At screening visit - normal	228 Participants	230 Participants	222 Participants
Change in Clinical Evaluation: Electrocardiogram (ECG) At screening visit - Abn, NCS	40 Participants	38 Participants	41 Participants
Change in Clinical Evaluation: Electrocardiogram (ECG) At screening visit - Abn, CS	7 Participants	3 Participants	10 Participants
Change in Clinical Evaluation: Electrocardiogram (ECG) Week 52 - normal	238 Participants	232 Participants	233 Participants
Change in Clinical Evaluation: Electrocardiogram (ECG) Week 52 - Abn, NCS	30 Participants	35 Participants	34 Participants
Change in Clinical Evaluation: Electrocardiogram (ECG) Week 52 - Abn, CS	7 Participants	4 Participants	6 Participants

SECONDARY outcome

Timeframe: Week 0, week 52

Population: Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparator (819 subjects). Subjects in the safety set contributed to the evaluation "as treated".

Change in pulse after 52 weeks of treatment.

Outcome measures

Outcome measures
Measure	Insulin Degludec/Liraglutide n=275 Participants Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec n=271 Participants Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide n=273 Participants Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.
Change in Clinical Evaluation: Pulse	3.9 beats per minute Standard Deviation 9.5	0.8 beats per minute Standard Deviation 8.9	4.2 beats per minute Standard Deviation 9.1

SECONDARY outcome

Timeframe: Weeks 2, 8, 16, 26, 44, 52

Population: Full Analysis Set (FAS) included all randomised subjects (819 subjects). All subjects in FAS with at least one valid concentration value were included in the analysis. No imputations of missing concentration values were applied. Number Analyzed = subjects with available data. This endpoint is only applicable for subjects in IDegLira and IDeg arm.

Samples from the IDegLira and IDeg arms were analysed for serum concentrations of insulin degludec using validated ELISA assays.

Outcome measures

Outcome measures
Measure	Insulin Degludec/Liraglutide n=275 Participants Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec n=271 Participants Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.
Serum Concentrations of Insulin Degludec At week 2	1468.7 pmol/L Geometric Coefficient of Variation 55.9	1477.1 pmol/L Geometric Coefficient of Variation 61.3	—
Serum Concentrations of Insulin Degludec At week 8	2246.0 pmol/L Geometric Coefficient of Variation 72.2	2524.6 pmol/L Geometric Coefficient of Variation 71.5	—
Serum Concentrations of Insulin Degludec At week 16	2511.0 pmol/L Geometric Coefficient of Variation 83.6	2856.4 pmol/L Geometric Coefficient of Variation 84.4	—
Serum Concentrations of Insulin Degludec At week 26	2597.3 pmol/L Geometric Coefficient of Variation 88.3	2946.9 pmol/L Geometric Coefficient of Variation 91.1	—
Serum Concentrations of Insulin Degludec At week 44	2766.6 pmol/L Geometric Coefficient of Variation 85.8	3238.8 pmol/L Geometric Coefficient of Variation 91.7	—
Serum Concentrations of Insulin Degludec At week 52	2393.8 pmol/L Geometric Coefficient of Variation 116.7	3124.4 pmol/L Geometric Coefficient of Variation 101.2	—

SECONDARY outcome

Timeframe: Weeks 2, 8, 16, 26, 44, 52

Population: Full Analysis Set (FAS) included all randomised subjects (819 subjects). All subjects in FAS with at least one valid concentration value were included in the analysis. No imputations of missing concentration values were applied. Number Analyzed = subjects with available data. This endpoint is only applicable for subjects in IDegLira and Lira arm.

Samples from the IDegLira and liraglutide arms were assayed for plasma concentrations of liraglutide using validated ELISA assays.

Outcome measures

Outcome measures
Measure	Insulin Degludec/Liraglutide n=275 Participants Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec n=273 Participants Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.
Plasma Concentrations of Liraglutide At week 2	5681.3 pmol/L Geometric Coefficient of Variation 49.4	6081.6 pmol/L Geometric Coefficient of Variation 65.4	—
Plasma Concentrations of Liraglutide At week 8	9107.8 pmol/L Geometric Coefficient of Variation 61.4	14539.5 pmol/L Geometric Coefficient of Variation 71.0	—
Plasma Concentrations of Liraglutide At week 16	10038.1 pmol/L Geometric Coefficient of Variation 69.5	14046.5 pmol/L Geometric Coefficient of Variation 73.0	—
Plasma Concentrations of Liraglutide At week 26	9995.3 pmol/L Geometric Coefficient of Variation 77.5	13904.2 pmol/L Geometric Coefficient of Variation 91.8	—
Plasma Concentrations of Liraglutide At week 44	8791.7 pmol/L Geometric Coefficient of Variation 81.0	12855.6 pmol/L Geometric Coefficient of Variation 112.7	—
Plasma Concentrations of Liraglutide At week 52	7426.2 pmol/L Geometric Coefficient of Variation 103.5	12127.4 pmol/L Geometric Coefficient of Variation 142.4	—

Adverse Events

Insulin Degludec/Liraglutide

Serious events: 17 serious events

Other events: 153 other events

Deaths: 1 deaths

Insulin Degludec

Serious events: 13 serious events

Other events: 137 other events

Deaths: 0 deaths

Liraglutide

Serious events: 14 serious events

Other events: 158 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Insulin Degludec/Liraglutide n=275 participants at risk Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Insulin Degludec n=271 participants at risk Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.	Liraglutide n=273 participants at risk Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended.
Gastrointestinal disorders Constipation	9.8% 27/275 • Number of events 28 • Week 0 (randomisation) to week 52 (end of treatment) and 7 days after end of treatment. Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.	4.4% 12/271 • Number of events 12 • Week 0 (randomisation) to week 52 (end of treatment) and 7 days after end of treatment. Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.	13.9% 38/273 • Number of events 42 • Week 0 (randomisation) to week 52 (end of treatment) and 7 days after end of treatment. Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.
Eye disorders Diabetic retinopathy	6.2% 17/275 • Number of events 17 • Week 0 (randomisation) to week 52 (end of treatment) and 7 days after end of treatment. Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.	4.4% 12/271 • Number of events 14 • Week 0 (randomisation) to week 52 (end of treatment) and 7 days after end of treatment. Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.	4.0% 11/273 • Number of events 11 • Week 0 (randomisation) to week 52 (end of treatment) and 7 days after end of treatment. Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.
Gastrointestinal disorders Diarrhoea	5.5% 15/275 • Number of events 20 • Week 0 (randomisation) to week 52 (end of treatment) and 7 days after end of treatment. Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.	4.4% 12/271 • Number of events 14 • Week 0 (randomisation) to week 52 (end of treatment) and 7 days after end of treatment. Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.	8.8% 24/273 • Number of events 31 • Week 0 (randomisation) to week 52 (end of treatment) and 7 days after end of treatment. Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.
Skin and subcutaneous tissue disorders Eczema	5.8% 16/275 • Number of events 18 • Week 0 (randomisation) to week 52 (end of treatment) and 7 days after end of treatment. Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.	2.2% 6/271 • Number of events 6 • Week 0 (randomisation) to week 52 (end of treatment) and 7 days after end of treatment. Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.	3.3% 9/273 • Number of events 10 • Week 0 (randomisation) to week 52 (end of treatment) and 7 days after end of treatment. Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.
Nervous system disorders Headache	2.5% 7/275 • Number of events 11 • Week 0 (randomisation) to week 52 (end of treatment) and 7 days after end of treatment. Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.	2.6% 7/271 • Number of events 12 • Week 0 (randomisation) to week 52 (end of treatment) and 7 days after end of treatment. Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.	5.5% 15/273 • Number of events 17 • Week 0 (randomisation) to week 52 (end of treatment) and 7 days after end of treatment. Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.
Infections and infestations Influenza	5.5% 15/275 • Number of events 15 • Week 0 (randomisation) to week 52 (end of treatment) and 7 days after end of treatment. Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.	3.3% 9/271 • Number of events 9 • Week 0 (randomisation) to week 52 (end of treatment) and 7 days after end of treatment. Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.	3.3% 9/273 • Number of events 9 • Week 0 (randomisation) to week 52 (end of treatment) and 7 days after end of treatment. Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.
Investigations Lipase increased	2.2% 6/275 • Number of events 8 • Week 0 (randomisation) to week 52 (end of treatment) and 7 days after end of treatment. Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.	0.00% 0/271 • Week 0 (randomisation) to week 52 (end of treatment) and 7 days after end of treatment. Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.	5.5% 15/273 • Number of events 15 • Week 0 (randomisation) to week 52 (end of treatment) and 7 days after end of treatment. Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.
Gastrointestinal disorders Nausea	3.3% 9/275 • Number of events 13 • Week 0 (randomisation) to week 52 (end of treatment) and 7 days after end of treatment. Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.	1.8% 5/271 • Number of events 7 • Week 0 (randomisation) to week 52 (end of treatment) and 7 days after end of treatment. Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.	8.4% 23/273 • Number of events 30 • Week 0 (randomisation) to week 52 (end of treatment) and 7 days after end of treatment. Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.
Infections and infestations Pharyngitis	4.0% 11/275 • Number of events 13 • Week 0 (randomisation) to week 52 (end of treatment) and 7 days after end of treatment. Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.	5.5% 15/271 • Number of events 18 • Week 0 (randomisation) to week 52 (end of treatment) and 7 days after end of treatment. Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.	3.3% 9/273 • Number of events 9 • Week 0 (randomisation) to week 52 (end of treatment) and 7 days after end of treatment. Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.
Infections and infestations Viral upper respiratory tract infection	38.5% 106/275 • Number of events 166 • Week 0 (randomisation) to week 52 (end of treatment) and 7 days after end of treatment. Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.	33.6% 91/271 • Number of events 161 • Week 0 (randomisation) to week 52 (end of treatment) and 7 days after end of treatment. Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.	34.4% 94/273 • Number of events 155 • Week 0 (randomisation) to week 52 (end of treatment) and 7 days after end of treatment. Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.
Investigations Weight increased	1.5% 4/275 • Number of events 4 • Week 0 (randomisation) to week 52 (end of treatment) and 7 days after end of treatment. Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.	7.0% 19/271 • Number of events 19 • Week 0 (randomisation) to week 52 (end of treatment) and 7 days after end of treatment. Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.	0.37% 1/273 • Number of events 1 • Week 0 (randomisation) to week 52 (end of treatment) and 7 days after end of treatment. Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.

Additional Information

Clinical Reporting Anchor and Disclosure (1452)

Novo Nordisk A/S

Phone: (+1) 866-867-7178

Email: [email protected]

Results disclosure agreements

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