Trial Outcomes & Findings for A Trial Comparing Insulin Degludec/Liraglutide and Insulin Degludec in Combination With Metformin in Chinese Subjects With Type 2 Diabetes Mellitus Inadequately Controlled With Basal Insulin Therapy and Metformin With or Without One Other Oral Antidiabetic Drug (OAD) (NCT NCT03175120)

NCT ID: NCT03175120

Last Updated: 2020-03-19

Results Overview

Change in glycosylated haemoglobin (HbA1c) from baseline (week 0) to week 26 is presented.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 453 participants
• Primary outcome timeframe: Week 0, week 26
• Results posted on: 2020-03-19

Participant Flow

The trial was conducted at 40 sites in China.

Participants were randomised in a 2:1 manner to receive either IDegLira or IDeg in combination with metformin.

Participant milestones

Measure	Insulin Degludec/Liraglutide Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Insulin Degludec Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.
Overall Study STARTED	302	151
Overall Study Treated	301	151
Overall Study Full Analysis Set (FAS)	302	151
Overall Study Safety Analysis Set (SAS)	301	151
Overall Study COMPLETED	290	139
Overall Study NOT COMPLETED	12	12

Reasons for withdrawal

Measure	Insulin Degludec/Liraglutide Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Insulin Degludec Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.
Overall Study Adverse Event	2	2
Overall Study Protocol Violation	5	2
Overall Study Lost to Follow-up	1	0
Overall Study Withdrawal by Subject	2	5
Overall Study Other	2	3

Baseline Characteristics

A Trial Comparing Insulin Degludec/Liraglutide and Insulin Degludec in Combination With Metformin in Chinese Subjects With Type 2 Diabetes Mellitus Inadequately Controlled With Basal Insulin Therapy and Metformin With or Without One Other Oral Antidiabetic Drug (OAD)

Baseline characteristics by cohort

Measure	Insulin Degludec/Liraglutide n=302 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Insulin Degludec n=151 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Total n=453 Participants Total of all reporting groups
Age, Continuous	54.5 Years STANDARD_DEVIATION 9.8 • n=5 Participants	55.3 Years STANDARD_DEVIATION 10.0 • n=7 Participants	54.7 Years STANDARD_DEVIATION 9.9 • n=5 Participants
Sex: Female, Male Female	119 Participants n=5 Participants	60 Participants n=7 Participants	179 Participants n=5 Participants
Sex: Female, Male Male	183 Participants n=5 Participants	91 Participants n=7 Participants	274 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	302 Participants n=5 Participants	151 Participants n=7 Participants	453 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	302 Participants n=5 Participants	151 Participants n=7 Participants	453 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Glycosylated haemoglobin (HbA1c)	8.93 Percentage of HbA1c STANDARD_DEVIATION 1.20 • n=5 Participants	8.96 Percentage of HbA1c STANDARD_DEVIATION 1.17 • n=7 Participants	8.94 Percentage of HbA1c STANDARD_DEVIATION 1.19 • n=5 Participants

PRIMARY outcome

Timeframe: Week 0, week 26

Population: FAS included all randomised participants. Overall number of participants analysed = participants with available data.

Change in glycosylated haemoglobin (HbA1c) from baseline (week 0) to week 26 is presented.

Outcome measures

Measure	Insulin Degludec n=138 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=289 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Change in HbA1c	-1.06 Percentage point of HbA1c Standard Deviation 1.19	-1.93 Percentage point of HbA1c Standard Deviation 1.14

SECONDARY outcome

Timeframe: Week 0, week 26

Population: FAS included all randomised participants. Overall number of participants analysed = participants with available data.

Change in body weight from baseline (week 0) to week 26 is presented.

Outcome measures

Measure	Insulin Degludec n=139 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=288 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Change in Body Weight	0.5 Kilogram (kg) Standard Deviation 2.7	-0.7 Kilogram (kg) Standard Deviation 3.0

SECONDARY outcome

Timeframe: Up to 26 weeks

Population: Safety analysis set (SAS) included all participants who received at least one dose of IDegLira or IDeg.

Severe or BG confirmed hypoglycaemic episodes were defined as episodes that were severe according to the American Diabetes Association (ADA) classification (requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or BG confirmed by a plasma glucose value < 3.1 millimoles per liter (mmol/L) with or without symptoms consistent with hypoglycaemia. Hypoglycaemic episodes were defined as treatment-emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product. Number of treatment-emergent severe or BG confirmed hypoglycaemic episodes during 26 weeks of treatment is presented.

Outcome measures

Measure	Insulin Degludec n=151 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=301 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Number of Treatment-emergent Severe or Blood Glucose (BG) Confirmed Hypoglycaemic Episodes	36 Episodes	38 Episodes

SECONDARY outcome

Timeframe: Week 0, week 26

Population: FAS included all randomised participants. Overall number of participants analysed = participants with available data.

Change in FPG from baseline (week 0) to week 26 is presented.

Outcome measures

Measure	Insulin Degludec n=139 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=289 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Change in Fasting Plasma Glucose (FPG)	-2.82 mmol/L Standard Deviation 3.15	-3.57 mmol/L Standard Deviation 3.00

SECONDARY outcome

Timeframe: Week 0, week 26

Population: FAS included all randomised participants. Overall number of participants analysed = participants with available data.

Change in waist circumference from baseline (week 0) to week 26 is presented.

Outcome measures

Measure	Insulin Degludec n=139 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=288 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Change in Waist Circumference	0.7 Centimeter (cm) Standard Deviation 3.3	-0.4 Centimeter (cm) Standard Deviation 4.3

SECONDARY outcome

Timeframe: Week 0, week 26

Population: FAS included all randomised participants. Overall number of participants analysed = participants with available data.

Participants measured plasma glucose values using the blood glucose meter at 9 time points: before breakfast, 90 min after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 min after start of dinner, bedtime, at 4:00 am and before breakfast the following day. The mean of profile is defined as the area under the profile divided by measurement time and is calculated using the trapezoidal method. Change in mean of the 9-point SMPG profile from baseline (week 0) to week 26 is presented.

Outcome measures

Measure	Insulin Degludec n=133 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=272 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Change in Mean of the 9-point Self-measured Plasma Glucose (SMPG) Profile	-2.31 mmol/L Standard Deviation 2.61	-3.35 mmol/L Standard Deviation 2.63

SECONDARY outcome

Timeframe: Week 0, week 26

Population: FAS included all randomised participants. Overall number of participants analysed = participants with available data.

Participants measured plasma glucose values using the blood glucose meter at 9 time points: before breakfast, 90 min after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 min after start of dinner, bedtime, at 4:00 am and before breakfast the following day. Change in SMPG-mean postprandial increment over all meals from baseline (week 0) to week 26 is presented.

Outcome measures

Measure	Insulin Degludec n=134 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=280 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Change in SMPG-mean Post Prandial Increments	0.28 mmol/L Standard Deviation 2.71	0.08 mmol/L Standard Deviation 2.19

SECONDARY outcome

Timeframe: Week 26

Population: SAS included all participants who received at least one dose of IDegLira or IDeg. Overall number of participants analysed = participants with available data.

The mean of actual daily total insulin dose after 26 weeks of treatment is presented.

Outcome measures

Measure	Insulin Degludec n=139 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=290 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Insulin Dose	37.9 Units of insulin (U) Standard Deviation 10.8	34.6 Units of insulin (U) Standard Deviation 11.1

SECONDARY outcome

Timeframe: Week 26

Population: FAS included all randomised participants. Number analysed = participants with available data.

Participants measured plasma glucose values using the blood glucose meter at 9 time points: before breakfast, 90 min after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 min after start of dinner, bedtime, at 4:00 am and before breakfast the following day. SMPG-9-point profile (individual points in the profile) at week 26 is presented.

Outcome measures

Measure	Insulin Degludec n=151 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=302 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
SMPG-9-point Profile (Individual Points in the Profile) Before breakfast	5.88 mmol/L Standard Deviation 1.30	5.48 mmol/L Standard Deviation 1.06
SMPG-9-point Profile (Individual Points in the Profile) 90 minutes after start of breakfast	10.50 mmol/L Standard Deviation 2.45	9.51 mmol/L Standard Deviation 2.66
SMPG-9-point Profile (Individual Points in the Profile) Before lunch	8.17 mmol/L Standard Deviation 3.19	6.93 mmol/L Standard Deviation 2.10
SMPG-9-point Profile (Individual Points in the Profile) 90 minutes after start of lunch	11.21 mmol/L Standard Deviation 2.93	9.68 mmol/L Standard Deviation 2.52
SMPG-9-point Profile (Individual Points in the Profile) Before main evening meal	7.87 mmol/L Standard Deviation 2.65	7.24 mmol/L Standard Deviation 2.16
SMPG-9-point Profile (Individual Points in the Profile) 90 minutes after main evening meal	10.86 mmol/L Standard Deviation 2.46	9.87 mmol/L Standard Deviation 2.53
SMPG-9-point Profile (Individual Points in the Profile) At bedtime	9.52 mmol/L Standard Deviation 2.61	8.57 mmol/L Standard Deviation 2.52
SMPG-9-point Profile (Individual Points in the Profile) At 4:00 a.m.	6.61 mmol/L Standard Deviation 1.99	5.97 mmol/L Standard Deviation 1.49
SMPG-9-point Profile (Individual Points in the Profile) Before breakfast the following day	5.83 mmol/L Standard Deviation 1.52	5.48 mmol/L Standard Deviation 1.14

SECONDARY outcome

Timeframe: Week 0, week 26

Population: FAS included all randomised participants. Overall number of participants analysed = participants with available data.

Change in fasting HDL cholesterol (measured in mmol/L) from baseline (week 0) to week 26 is presented as ratio to baseline.

Outcome measures

Measure	Insulin Degludec n=139 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=289 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Change in Fasting High-density Lipoprotein (HDL) Cholesterol- Ratio to Baseline	1.03 Ratio of HDL cholesterol Geometric Coefficient of Variation 15.9	1.00 Ratio of HDL cholesterol Geometric Coefficient of Variation 17.5

SECONDARY outcome

Timeframe: Week 0, week 26

Population: FAS included all randomised participants. Overall number of participants analysed = participants with available data.

Change in fasting LDL cholesterol (measured in mmol/L) from baseline (week 0) to week 26 is presented as ratio to baseline.

Outcome measures

Measure	Insulin Degludec n=134 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=284 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Change in Fasting Low-density Lipoprotein (LDL) Cholesterol- Ratio to Baseline	0.95 Ratio of LDL cholesterol Geometric Coefficient of Variation 37.7	0.89 Ratio of LDL cholesterol Geometric Coefficient of Variation 32.5

SECONDARY outcome

Timeframe: Week 0, week 26

Population: FAS included all randomised participants. Overall number of participants analysed = participants with available data.

Change in fasting VLDL cholesterol (measured in mmol/L) from baseline (week 0) to week 26 is presented as ratio to baseline.

Outcome measures

Measure	Insulin Degludec n=139 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=289 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Change in Fasting Very Low-density Lipoprotein (VLDL) Cholesterol- Ratio to Baseline	0.93 Ratio of VLDL cholesterol Geometric Coefficient of Variation 49.1	0.92 Ratio of VLDL cholesterol Geometric Coefficient of Variation 55.2

SECONDARY outcome

Timeframe: Week 0, week 26

Population: FAS included all randomised participants. Overall number of participants analysed = participants with available data.

Change in fasting total cholesterol (measured in mmol/L) from baseline (week 0) to week 26 is presented as ratio to baseline.

Outcome measures

Measure	Insulin Degludec n=139 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=289 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Change in Fasting Total Cholesterol- Ratio to Baseline	0.97 Ratio of total cholesterol Geometric Coefficient of Variation 20.0	0.92 Ratio of total cholesterol Geometric Coefficient of Variation 19.1

SECONDARY outcome

Timeframe: Week 0, week 26

Population: FAS included all randomised participants. Overall number of participants analysed = participants with available data.

Change in fasting triglycerides (measured in mmol/L) from baseline (week 0) to week 26 is presented as ratio to baseline.

Outcome measures

Measure	Insulin Degludec n=139 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=289 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Change in Fasting Triglycerides- Ratio to Baseline	0.92 Ratio of triglycerides Geometric Coefficient of Variation 55.8	0.91 Ratio of triglycerides Geometric Coefficient of Variation 63.7

SECONDARY outcome

Timeframe: Week 0, week 26

Population: FAS included all randomised participants. Overall number of participants analysed = participants with available data.

Change in fasting free fatty acids (measured in mmol/L) from baseline (week 0) to week 26 is presented as ratio to baseline.

Outcome measures

Measure	Insulin Degludec n=138 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=289 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Change in Fasting Free Fatty Acids- Ratio to Baseline	0.64 Ratio of free fatty acids Geometric Coefficient of Variation 61.9	0.65 Ratio of free fatty acids Geometric Coefficient of Variation 76.4

SECONDARY outcome

Timeframe: Week 0, week 26

Population: FAS included all randomised participants. Overall number of participants analysed = participants with available data.

Change in fasting C-peptide (measured in nanomoles per liter (nmol/L)) from baseline (week 0) to week 26 is presented as ratio to baseline.

Outcome measures

Measure	Insulin Degludec n=137 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=286 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Change in Fasting C-peptide- Ratio to Baseline	0.52 Ratio of C-peptide Geometric Coefficient of Variation 71.8	0.64 Ratio of C-peptide Geometric Coefficient of Variation 71.2

SECONDARY outcome

Timeframe: Week 0, week 26

Population: FAS included all randomised participants. Overall number of participants analysed = participants with available data.

Change in fasting insulin (measured in picomoles per liter (pmol/L)) from baseline (week 0) to week 26 is presented as ratio to baseline.

Outcome measures

Measure	Insulin Degludec n=139 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=288 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Change in Fasting Insulin- Ratio to Baseline	0.50 Ratio of insulin Geometric Coefficient of Variation 106.4	0.63 Ratio of insulin Geometric Coefficient of Variation 118.3

SECONDARY outcome

Timeframe: Week 0, week 26

Population: FAS included all randomised participants. Overall number of participants analysed = participants with available data.

Change in fasting glucagon (measured in picograms per milliliter (pg/mL)) from baseline (week 0) to week 26 is presented as ratio to baseline.

Outcome measures

Measure	Insulin Degludec n=138 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=287 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Change in Fasting Glucagon- Ratio to Baseline	1.09 Ratio of glucagon Geometric Coefficient of Variation 81.7	1.01 Ratio of glucagon Geometric Coefficient of Variation 95.8

SECONDARY outcome

Timeframe: Week 0, week 26

Population: FAS included all randomised participants. Overall number of participants analysed = participants with available data.

Change in HOMA-B from baseline (week 0) to week 26 is presented as ratio to baseline.

Outcome measures

Measure	Insulin Degludec n=139 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=287 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Change in HOMA-B (Beta-cell Function)- Ratio to Baseline	0.99 Ratio of beta-cell function Geometric Coefficient of Variation 113.4	1.47 Ratio of beta-cell function Geometric Coefficient of Variation 115.0

SECONDARY outcome

Timeframe: Week 26

Population: FAS included all randomised participants. Overall number of participants analysed = participants with available data.

Participants who achieved HbA1c < 7.0%, ADA target (yes/no) is presented.

Outcome measures

Measure	Insulin Degludec n=138 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=289 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Participants Who Achieved HbA1c < 7.0%, ADA Target (Yes/no) Yes	23 Participants	151 Participants
Participants Who Achieved HbA1c < 7.0%, ADA Target (Yes/no) No	115 Participants	138 Participants

SECONDARY outcome

Timeframe: Week 26

Population: FAS included all randomised participants. Overall number of participants analysed = participants with available data.

Participants who achieved HbA1c ≤ 6.5%, AACE target (yes/no) is presented.

Outcome measures

Measure	Insulin Degludec n=138 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=289 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Participants Who Achieved HbA1c ≤ 6.5%, American Association of Clinical Endocrinologists (AACE) Target (Yes/no) Yes	10 Participants	96 Participants
Participants Who Achieved HbA1c ≤ 6.5%, American Association of Clinical Endocrinologists (AACE) Target (Yes/no) No	128 Participants	193 Participants

SECONDARY outcome

Timeframe: Week 26

Population: FAS included all randomised participants. Overall number of participants analysed = participants with available data.

Participants who achieved HbA1c < 7.0% and change from baseline in body weight below or equal to zero is presented.

Outcome measures

Measure	Insulin Degludec n=151 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=302 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Participants Who Achieved HbA1c < 7.0% and Change From Baseline in Body Weight Below or Equal to Zero Yes	7 Participants	98 Participants
Participants Who Achieved HbA1c < 7.0% and Change From Baseline in Body Weight Below or Equal to Zero No	144 Participants	204 Participants

SECONDARY outcome

Timeframe: Week 26

Population: FAS included all randomised participants. Overall number of participants analysed = participants with available data.

Participants who achieved HbA1c ≤ 6.5% and change from baseline in body weight below or equal to zero is presented.

Outcome measures

Measure	Insulin Degludec n=151 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=302 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Participants Who Achieved HbA1c ≤ 6.5% and Change From Baseline in Body Weight Below or Equal to Zero Yes	3 Participants	59 Participants
Participants Who Achieved HbA1c ≤ 6.5% and Change From Baseline in Body Weight Below or Equal to Zero No	148 Participants	243 Participants

SECONDARY outcome

Timeframe: Week 26

Population: FAS included all randomised participants. Overall number of participants analysed = participants with available data.

Severe or BG confirmed hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification (required assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or BG confirmed by a plasma glucose value < 3.1 mmol/L with or without symptoms consistent with hypoglycaemia. Hypoglycaemic episodes were defined as treatment-emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product. Participants who achieved HbA1c < 7.0% at week 26 without treatment-emergent severe or BG confirmed hypoglycaemic episodes during the last 12 weeks of treatment is presented.

Outcome measures

Measure	Insulin Degludec n=151 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=302 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Participants Who Achieved HbA1c < 7.0% Without Treatment-emergent Severe or BG Confirmed Hypoglycaemic Episodes Yes	22 Participants	148 Participants
Participants Who Achieved HbA1c < 7.0% Without Treatment-emergent Severe or BG Confirmed Hypoglycaemic Episodes No	129 Participants	154 Participants

SECONDARY outcome

Timeframe: Week 26

Population: FAS included all randomised participants. Overall number of participants analysed = participants with available data.

Severe or BG confirmed hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification (required assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or BG confirmed by a plasma glucose value < 3.1 mmol/L with or without symptoms consistent with hypoglycaemia. Hypoglycaemic episodes were defined as treatment-emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product. Participants who achieved HbA1c ≤ 6.5% at week 26 without treatment-emergent severe or BG confirmed hypoglycaemic episodes during the last 12 weeks of treatment is presented.

Outcome measures

Measure	Insulin Degludec n=151 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=302 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Participants Who Achieved HbA1c ≤ 6.5% Without Treatment-emergent Severe or BG Confirmed Hypoglycaemic Episodes Yes	9 Participants	93 Participants
Participants Who Achieved HbA1c ≤ 6.5% Without Treatment-emergent Severe or BG Confirmed Hypoglycaemic Episodes No	142 Participants	209 Participants

SECONDARY outcome

Timeframe: Week 26

Population: FAS included all randomised participants. Overall number of participants analysed = participants with available data.

Severe or BG confirmed hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification (required assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or BG confirmed by a plasma glucose value < 3.1 mmol/L with or without symptoms consistent with hypoglycaemia. Hypoglycaemic episodes were defined as treatment-emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product. Participants who achieved HbA1c < 7.0% and change from baseline in body weight below or equal to zero and without treatment-emergent severe or BG confirmed hypoglycaemic episodes during the last 12 weeks of treatment is presented.

Outcome measures

Measure	Insulin Degludec n=151 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=302 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Participants Who Achieved HbA1c < 7.0% and Change From Baseline in Body Weight Below or Equal to Zero and Without Treatment-emergent Severe or BG Confirmed Hypoglycaemic Episodes Yes	7 Participants	94 Participants
Participants Who Achieved HbA1c < 7.0% and Change From Baseline in Body Weight Below or Equal to Zero and Without Treatment-emergent Severe or BG Confirmed Hypoglycaemic Episodes No	144 Participants	208 Participants

SECONDARY outcome

Timeframe: Week 26

Population: FAS included all randomised participants. Overall number of participants analysed = participants with available data.

Severe or BG confirmed hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification (required assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or BG confirmed by a plasma glucose value < 3.1 mmol/L with or without symptoms consistent with hypoglycaemia. Hypoglycaemic episodes were defined as treatment-emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product. Participants who achieved HbA1c ≤ 6.5% and change from baseline in body weight below or equal to zero and without treatment-emergent severe or BG confirmed hypoglycaemic episodes during the last 12 weeks of treatment is presented.

Outcome measures

Measure	Insulin Degludec n=151 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=302 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Participants Who Achieved HbA1c ≤ 6.5% and Change From Baseline in Body Weight Below or Equal to Zero and Without Treatment-emergent Severe or BG Confirmed Hypoglycaemic Episodes Yes	3 Participants	58 Participants
Participants Who Achieved HbA1c ≤ 6.5% and Change From Baseline in Body Weight Below or Equal to Zero and Without Treatment-emergent Severe or BG Confirmed Hypoglycaemic Episodes No	148 Participants	244 Participants

SECONDARY outcome

Timeframe: Weeks 0-27

Population: SAS included all participants who received at least one dose of IDegLira or IDeg.

A TEAE was defined as an adverse event with onset date on or after the first day of exposure to randomised treatment and no later than seven days after the last day of randomised treatment. 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

Measure	Insulin Degludec n=151 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=301 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Number of Treatment-emergent Adverse Events (TEAEs)	230 Adverse events	641 Adverse events

SECONDARY outcome

Timeframe: Weeks 0-27

Population: SAS included all participants who received at least one dose of IDegLira or IDeg.

Severe or BG confirmed hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification (required assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or BG confirmed by a plasma glucose value < 3.1 mmol/L with or without symptoms consistent with hypoglycaemia. Hypoglycaemic episodes were defined as treatment-emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product. Nocturnal hypoglycaemic episodes were episodes occurring between 00:01 and 05.59 a.m. both inclusive. Number of treatment-emergent nocturnal severe or BG confirmed hypoglycaemic episodes is presented.

Outcome measures

Measure	Insulin Degludec n=151 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=301 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Number of Treatment-emergent Nocturnal Severe or BG Confirmed Hypoglycaemic Episodes	8 Episodes	9 Episodes

SECONDARY outcome

Timeframe: Weeks 0-27

Population: SAS included all participants who received at least one dose of IDegLira or IDeg.

Severe or BG confirmed hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification (required assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or BG confirmed by a plasma glucose value < 3.1 mmol/L with symptoms consistent with hypoglycaemia. Hypoglycaemic episodes were defined as treatment-emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product. Number of treatment-emergent severe or BG confirmed symptomatic hypoglycaemic episodes is presented.

Outcome measures

Measure	Insulin Degludec n=151 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=301 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Number of Treatment-emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes	21 Episodes	23 Episodes

SECONDARY outcome

Timeframe: Weeks 0-27

Population: SAS included all participants who received at least one dose of IDegLira or IDeg.

Severe or BG confirmed hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification (required assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or BG confirmed by a plasma glucose value < 3.1 mmol/L with symptoms consistent with hypoglycaemia. Hypoglycaemic episodes were defined as treatment-emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product. Nocturnal hypoglycaemic episodes were episodes occurring between 00:01 and 05.59 a.m. both inclusive. Number of treatment-emergent nocturnal severe or BG confirmed symptomatic hypoglycaemic episodes is presented.

Outcome measures

Measure	Insulin Degludec n=151 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=301 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Number of Treatment-emergent Nocturnal Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes	7 Episodes	7 Episodes

SECONDARY outcome

Timeframe: Weeks 0-27

Population: SAS included all participants who received at least one dose of IDegLira or IDeg.

Hypoglycaemic episodes were defined as treatment-emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product. Number of treatment-emergent hypoglycaemic episodes according to ADA definition is presented.

Outcome measures

Measure	Insulin Degludec n=151 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=301 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Number of Treatment-emergent Hypoglycaemic Episodes According to ADA Definition	680 Episodes	1099 Episodes

SECONDARY outcome

Timeframe: Week -2, week 26

Population: SAS included all participants who received at least one dose of IDegLira or IDeg. "Number analyzed"=participants with available data.

Physical examination parameters are categorised as cardiovascular system; central and peripheral nervous system; gastrointestinal system including mouth; general appearance; head, ears, eyes, nose, throat, neck; lymph node palpation; musculoskeletal system; respiratory system; skin and thyroid gland. The number of participants assessed as normal, abnormal not clinically significant (NCS) and abnormal clinically significant (CS) at week -2 and week 26 is presented.

Outcome measures

Measure	Insulin Degludec n=151 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=301 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Change in Physical Examination Week-2: Cardiovascular system · Normal	149 Participants	299 Participants
Change in Physical Examination Week-2: Cardiovascular system · Abnormal NCS	0 Participants	1 Participants
Change in Physical Examination Week-2: Cardiovascular system · Abnormal CS	2 Participants	1 Participants
Change in Physical Examination Week 26: Cardiovascular system · Normal	137 Participants	286 Participants
Change in Physical Examination Week 26: Cardiovascular system · Abnormal NCS	0 Participants	1 Participants
Change in Physical Examination Week 26: Cardiovascular system · Abnormal CS	2 Participants	1 Participants
Change in Physical Examination Week-2: Central and peripheral nervous system · Normal	150 Participants	299 Participants
Change in Physical Examination Week-2: Central and peripheral nervous system · Abnormal NCS	0 Participants	2 Participants
Change in Physical Examination Week-2: Central and peripheral nervous system · Abnormal CS	1 Participants	0 Participants
Change in Physical Examination Week 26: Central and peripheral nervous system · Normal	139 Participants	287 Participants
Change in Physical Examination Week 26: Central and peripheral nervous system · Abnormal NCS	0 Participants	1 Participants
Change in Physical Examination Week 26: Central and peripheral nervous system · Abnormal CS	0 Participants	0 Participants
Change in Physical Examination Week -2: Gastrointestinal system · Normal	150 Participants	299 Participants
Change in Physical Examination Week -2: Gastrointestinal system · Abnormal NCS	1 Participants	2 Participants
Change in Physical Examination Week -2: Gastrointestinal system · Abnormal CS	0 Participants	0 Participants
Change in Physical Examination Week 26: Gastrointestinal system · Normal	139 Participants	285 Participants
Change in Physical Examination Week 26: Gastrointestinal system · Abnormal NCS	0 Participants	2 Participants
Change in Physical Examination Week 26: Gastrointestinal system · Abnormal CS	0 Participants	1 Participants
Change in Physical Examination Week -2: General appearance · Normal	141 Participants	283 Participants
Change in Physical Examination Week -2: General appearance · Abnormal NCS	2 Participants	11 Participants
Change in Physical Examination Week -2: General appearance · Abnormal CS	8 Participants	7 Participants
Change in Physical Examination Week 26: General appearance · Normal	130 Participants	273 Participants
Change in Physical Examination Week 26: General appearance · Abnormal NCS	2 Participants	9 Participants
Change in Physical Examination Week 26: General appearance · Abnormal CS	7 Participants	6 Participants
Change in Physical Examination Week -2: Head, eyes, ENTand Neck · Normal	147 Participants	295 Participants
Change in Physical Examination Week -2: Head, eyes, ENTand Neck · Abnormal NCS	2 Participants	2 Participants
Change in Physical Examination Week -2: Head, eyes, ENTand Neck · Abnormal CS	2 Participants	4 Participants
Change in Physical Examination Week 26: Head, eyes, ENTand Neck · Normal	137 Participants	283 Participants
Change in Physical Examination Week 26: Head, eyes, ENTand Neck · Abnormal NCS	1 Participants	2 Participants
Change in Physical Examination Week 26: Head, eyes, ENTand Neck · Abnormal CS	1 Participants	3 Participants
Change in Physical Examination Week -2: Lymph node palpation · Normal	151 Participants	301 Participants
Change in Physical Examination Week -2: Lymph node palpation · Abnormal NCS	0 Participants	0 Participants
Change in Physical Examination Week -2: Lymph node palpation · Abnormal CS	0 Participants	0 Participants
Change in Physical Examination Week 26: Lymph node palpation · Normal	139 Participants	288 Participants
Change in Physical Examination Week 26: Lymph node palpation · Abnormal NCS	0 Participants	0 Participants
Change in Physical Examination Week 26: Lymph node palpation · Abnormal CS	0 Participants	0 Participants
Change in Physical Examination Week -2: Musculoskeletal system · Normal	145 Participants	296 Participants
Change in Physical Examination Week -2: Musculoskeletal system · Abnormal NCS	3 Participants	2 Participants
Change in Physical Examination Week -2: Musculoskeletal system · Abnormal CS	3 Participants	3 Participants
Change in Physical Examination Week 26: Musculoskeletal system · Normal	137 Participants	280 Participants
Change in Physical Examination Week 26: Musculoskeletal system · Abnormal NCS	1 Participants	3 Participants
Change in Physical Examination Week 26: Musculoskeletal system · Abnormal CS	1 Participants	5 Participants
Change in Physical Examination Week -2: Respiratory system · Normal	151 Participants	301 Participants
Change in Physical Examination Week -2: Respiratory system · Abnormal NCS	0 Participants	0 Participants
Change in Physical Examination Week -2: Respiratory system · Abnormal CS	0 Participants	0 Participants
Change in Physical Examination Week 26: Respiratory system · Normal	139 Participants	288 Participants
Change in Physical Examination Week 26: Respiratory system · Abnormal NCS	0 Participants	0 Participants
Change in Physical Examination Week 26: Respiratory system · Abnormal CS	0 Participants	0 Participants
Change in Physical Examination Week -2: Skin · Normal	132 Participants	270 Participants
Change in Physical Examination Week -2: Skin · Abnormal NCS	13 Participants	22 Participants
Change in Physical Examination Week -2: Skin · Abnormal CS	6 Participants	9 Participants
Change in Physical Examination Week 26: Skin · Normal	126 Participants	259 Participants
Change in Physical Examination Week 26: Skin · Abnormal NCS	9 Participants	22 Participants
Change in Physical Examination Week 26: Skin · Abnormal CS	4 Participants	7 Participants
Change in Physical Examination Week -2: Thyroid gland · Normal	147 Participants	295 Participants
Change in Physical Examination Week -2: Thyroid gland · Abnormal NCS	2 Participants	4 Participants
Change in Physical Examination Week -2: Thyroid gland · Abnormal CS	2 Participants	2 Participants
Change in Physical Examination Week 26: Thyroid gland · Normal	134 Participants	284 Participants
Change in Physical Examination Week 26: Thyroid gland · Abnormal NCS	3 Participants	3 Participants
Change in Physical Examination Week 26: Thyroid gland · Abnormal CS	2 Participants	1 Participants

SECONDARY outcome

Timeframe: Week -2, week 26

Population: SAS included all participants who received at least one dose of IDegLira or IDeg. "Number analyzed"=participants with available data.

Dilated fundoscopy or fundus photography was performed by the investigator at week -2 and week 26. The results of the examination were interpreted for each eye (left/right) are categorised as normal, abnormal NCS or abnormal CS. Number of participants in each category at week -2 and week 26 were presented.

Outcome measures

Measure	Insulin Degludec n=151 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=301 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Eye Examination Week -2: Left eye · Normal	87 Participants	167 Participants
Eye Examination Week -2: Left eye · Abnormal NCS	15 Participants	34 Participants
Eye Examination Week -2: Left eye · Abnormal CS	49 Participants	100 Participants
Eye Examination Week 26: Left eye · Normal	80 Participants	147 Participants
Eye Examination Week 26: Left eye · Abnormal NCS	14 Participants	35 Participants
Eye Examination Week 26: Left eye · Abnormal CS	45 Participants	105 Participants
Eye Examination Week -2: Right eye · Normal	85 Participants	162 Participants
Eye Examination Week -2: Right eye · Abnormal NCS	18 Participants	41 Participants
Eye Examination Week -2: Right eye · Abnormal CS	47 Participants	98 Participants
Eye Examination Week 26: Right eye · Normal	84 Participants	139 Participants
Eye Examination Week 26: Right eye · Abnormal NCS	12 Participants	37 Participants
Eye Examination Week 26: Right eye · Abnormal CS	42 Participants	111 Participants

SECONDARY outcome

Timeframe: Week -2, week 26

Population: SAS included all participants who received at least one dose of IDegLira or IDeg. "Number analyzed"=participants with available data.

The ECG was assessed by the investigator at baseline (week -2) and week 26 and categorised as normal, abnormal NCS or abnormal CS. Number of participants in each ECG category at baseline and week 26 were presented.

Outcome measures

Measure	Insulin Degludec n=151 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=301 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Change in Electrocardiogram (ECG) Week -2 · Normal	90 Participants	175 Participants
Change in Electrocardiogram (ECG) Week -2 · Abnormal NCS	41 Participants	76 Participants
Change in Electrocardiogram (ECG) Week -2 · Abnormal CS	20 Participants	50 Participants
Change in Electrocardiogram (ECG) Week 26 · Normal	91 Participants	175 Participants
Change in Electrocardiogram (ECG) Week 26 · Abnormal NCS	32 Participants	73 Participants
Change in Electrocardiogram (ECG) Week 26 · Abnormal CS	16 Participants	39 Participants

SECONDARY outcome

Timeframe: Week 0, week 26

Population: SAS included all participants who received at least one dose of IDegLira or IDeg. Overall number of participants analyzed = participants with available data.

Change in pulse from baseline (week 0) to week 26 is presented.

Outcome measures

Measure	Insulin Degludec n=139 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=288 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Change in Pulse	1.3 Beats per minute (beats/min) Standard Deviation 8.7	5.7 Beats per minute (beats/min) Standard Deviation 9.6

SECONDARY outcome

Timeframe: Week 0, week 26

Population: SAS included all participants who received at least one dose of IDegLira or IDeg. Overall number of participants analysed = participants with available data.

Change in blood pressure (systolic and diastolic blood pressure) from baseline (week 0) to week 26 is presented.

Outcome measures

Measure	Insulin Degludec n=139 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=288 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Change in Blood Pressure (Systolic and Diastolic Blood Pressure) Systolic blood pressure	-0.5 Millimeters of mercury (mmHg) Standard Deviation 12.5	-3.5 Millimeters of mercury (mmHg) Standard Deviation 13.6
Change in Blood Pressure (Systolic and Diastolic Blood Pressure) Diastolic blood pressure	-0.4 Millimeters of mercury (mmHg) Standard Deviation 8.1	0.1 Millimeters of mercury (mmHg) Standard Deviation 7.8

SECONDARY outcome

Timeframe: Week 0, week 26

Population: SAS included all participants who received at least one dose of IDegLira or IDeg. Number analyzed = participants with available data.

Change in amylase, lipase, creatinine kinase, ALT, AST, ALP from baseline (week 0) to week 26 is presented.

Outcome measures

Measure	Insulin Degludec n=139 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=289 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Change in Biochemical Parameter- Amylase, Lipase, Creatinine Kinase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) Amylase	2.69 Units per liter (U/L) Standard Deviation 11.72	10.45 Units per liter (U/L) Standard Deviation 23.14
Change in Biochemical Parameter- Amylase, Lipase, Creatinine Kinase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) Lipase	-0.35 Units per liter (U/L) Standard Deviation 13.81	16.97 Units per liter (U/L) Standard Deviation 35.24
Change in Biochemical Parameter- Amylase, Lipase, Creatinine Kinase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) Creatinine kinase	6.99 Units per liter (U/L) Standard Deviation 84.31	3.32 Units per liter (U/L) Standard Deviation 65.17
Change in Biochemical Parameter- Amylase, Lipase, Creatinine Kinase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) ALT	-4.06 Units per liter (U/L) Standard Deviation 11.97	-3.02 Units per liter (U/L) Standard Deviation 12.03
Change in Biochemical Parameter- Amylase, Lipase, Creatinine Kinase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) AST	-2.06 Units per liter (U/L) Standard Deviation 7.92	-1.42 Units per liter (U/L) Standard Deviation 7.46
Change in Biochemical Parameter- Amylase, Lipase, Creatinine Kinase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) ALP	-1.70 Units per liter (U/L) Standard Deviation 11.39	-1.62 Units per liter (U/L) Standard Deviation 13.30

SECONDARY outcome

Timeframe: Week 0, week 26

Population: SAS included all participants who received at least one dose of IDegLira or IDeg. Number analyzed = participants with available data.

Change in calcium (total), albumin corrected calcium, potassium, sodium, urea from baseline (week 0) to week 26 is presented.

Outcome measures

Measure	Insulin Degludec n=139 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=289 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Change in Biochemical Parameter-calcium (Total), Albumin Corrected Calcium, Potassium, Sodium, Urea Calcium (total)	-0.01 mmol/L Standard Deviation 0.09	0.01 mmol/L Standard Deviation 0.10
Change in Biochemical Parameter-calcium (Total), Albumin Corrected Calcium, Potassium, Sodium, Urea Albumin corrected calcium	-0.01 mmol/L Standard Deviation 0.08	-0.00 mmol/L Standard Deviation 0.08
Change in Biochemical Parameter-calcium (Total), Albumin Corrected Calcium, Potassium, Sodium, Urea Potassium	-0.11 mmol/L Standard Deviation 0.35	-0.03 mmol/L Standard Deviation 0.34
Change in Biochemical Parameter-calcium (Total), Albumin Corrected Calcium, Potassium, Sodium, Urea Sodium	1.40 mmol/L Standard Deviation 2.43	1.03 mmol/L Standard Deviation 2.47
Change in Biochemical Parameter-calcium (Total), Albumin Corrected Calcium, Potassium, Sodium, Urea Urea	0.17 mmol/L Standard Deviation 1.29	-0.09 mmol/L Standard Deviation 1.32

SECONDARY outcome

Timeframe: Week 0, week 26

Population: SAS included all participants who received at least one dose of IDegLira or IDeg. Overall number of participants analyzed = participants with available data.

Change in albumin from baseline (week 0) to week 26 is presented.

Outcome measures

Measure	Insulin Degludec n=139 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=288 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Change in Albumin	0.02 Grams per deciliter (g/dL) Standard Deviation 0.25	0.05 Grams per deciliter (g/dL) Standard Deviation 0.29

SECONDARY outcome

Timeframe: Week 0, week 26

Population: SAS included all participants who received at least one dose of IDegLira or IDeg. Overall number of participants analyzed = participants with available data.

Change in total bilirubin from baseline (week 0) to week 26 is presented.

Outcome measures

Measure	Insulin Degludec n=139 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=289 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Change in Total Bilirubin	-0.54 Micromoles per liter (umol/L) Standard Deviation 3.66	-0.30 Micromoles per liter (umol/L) Standard Deviation 3.89

SECONDARY outcome

Timeframe: Week 0, week 26

Population: SAS included all participants who received at least one dose of IDegLira or IDeg. Overall number of participants analyzed = participants with available data.

Change in creatinine from baseline (week 0) to week 26 is presented.

Outcome measures

Measure	Insulin Degludec n=139 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=289 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Change in Creatinine	-0.32 umol/L Standard Deviation 7.52	0.44 umol/L Standard Deviation 7.93

SECONDARY outcome

Timeframe: Week 0, week 26

Population: SAS included all participants who received at least one dose of IDegLira or IDeg. Overall number of participants analyzed = participants with available data.

Change in total protein from baseline (week 0) to week 26 is presented.

Outcome measures

Measure	Insulin Degludec n=139 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=289 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Change in Total Protein	0.03 g/dL Standard Deviation 0.39	0.08 g/dL Standard Deviation 0.41

SECONDARY outcome

Timeframe: Week 0, week 26

Population: SAS included all participants who received at least one dose of IDegLira or IDeg. Overall number of participants analyzed = participants with available data.

Change in haematocrit from baseline (week 0) to week 26 is presented.

Outcome measures

Measure	Insulin Degludec n=139 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=289 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Change in Haematological Parameter- Haematocrit	-0.12 Percentage of red blood cells Standard Deviation 2.14	-0.07 Percentage of red blood cells Standard Deviation 2.56

SECONDARY outcome

Timeframe: Week 0, week 26

Population: SAS included all participants who received at least one dose of IDegLira or IDeg. Overall number of participants analyzed = participants with available data.

Change in haemoglobin from baseline (week 0) to week 26 is presented.

Outcome measures

Measure	Insulin Degludec n=139 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=288 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Change in Haematological Parameter- Haemoglobin	-0.09 mmol/L Standard Deviation 0.41	-0.08 mmol/L Standard Deviation 0.52

SECONDARY outcome

Timeframe: Week 0, week 26

Population: SAS included all participants who received at least one dose of IDegLira or IDeg. Number of participants analyzed = participants with available data.

Change in leukocytes and thrombocytes from baseline (week 0) to week 26 is presented.

Outcome measures

Measure	Insulin Degludec n=138 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=289 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Change in Haematological Parameter- Leukocytes and Thrombocytes Leukocytes	0.31 10^9 cells per liter (10^9/L) Standard Deviation 1.18	0.32 10^9 cells per liter (10^9/L) Standard Deviation 1.39
Change in Haematological Parameter- Leukocytes and Thrombocytes Thrombocytes	12.19 10^9 cells per liter (10^9/L) Standard Deviation 34.01	14.13 10^9 cells per liter (10^9/L) Standard Deviation 34.34

SECONDARY outcome

Timeframe: Week 0, week 26

Population: SAS included all participants who received at least one dose of IDegLira or IDeg. Overall number of participants analyzed = participants with available data.

Change in erythrocytes from baseline (week 0) to week 26 is presented.

Outcome measures

Measure	Insulin Degludec n=139 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=289 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Change in Haematological Parameter- Erythrocytes	-0.05 10^12 cells per liter (10^12/L) Standard Deviation 0.24	-0.06 10^12 cells per liter (10^12/L) Standard Deviation 0.26

SECONDARY outcome

Timeframe: Week 0, week 26

Population: SAS included all participants who received at least one dose of IDegLira or IDeg. Overall number of participants analyzed = participants with available data.

Change in basophils from baseline (week 0) to week 26 is presented.

Outcome measures

Measure	Insulin Degludec n=138 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=289 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Change in Haematological Parameter- Basophils	0.01 Percentage of basophils Standard Deviation 0.27	0.00 Percentage of basophils Standard Deviation 0.34

SECONDARY outcome

Timeframe: Week 0, week 26

Population: SAS included all participants who received at least one dose of IDegLira or IDeg. Overall number of participants analyzed = participants with available data.

Change in eosinophils from baseline (week 0) to week 26 is presented.

Outcome measures

Measure	Insulin Degludec n=138 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=289 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Change in Haematological Parameter- Eosinophils	-0.25 Percentage of eosinophils Standard Deviation 1.72	-0.15 Percentage of eosinophils Standard Deviation 1.84

SECONDARY outcome

Timeframe: Week 0, week 26

Population: SAS included all participants who received at least one dose of IDegLira or IDeg. Overall number of participants analyzed = participants with available data.

Change in lymphocytes from baseline (week 0) to week 26 is presented.

Outcome measures

Measure	Insulin Degludec n=138 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=289 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Change in Haematological Parameter- Lymphocytes	-0.82 Percentage of lymphocytes Standard Deviation 6.41	-1.00 Percentage of lymphocytes Standard Deviation 6.95

SECONDARY outcome

Timeframe: Week 0, week 26

Population: SAS included all participants who received at least one dose of IDegLira or IDeg. Overall number of participants analyzed = participants with available data.

Change in monocytes from baseline (week 0) to week 26 is presented.

Outcome measures

Measure	Insulin Degludec n=138 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=289 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Change in Haematological Parameter- Monocytes	-0.06 Percentage of monocytes Standard Deviation 2.19	-0.19 Percentage of monocytes Standard Deviation 2.02

SECONDARY outcome

Timeframe: Week 0, week 26

Population: SAS included all participants who received at least one dose of IDegLira or IDeg. Overall number of participants analyzed = participants with available data.

Change in neutrophils from baseline (week 0) to week 26 is presented.

Outcome measures

Measure	Insulin Degludec n=138 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=289 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Change in Haematological Parameter- Neutrophils	0.99 Percentage of neutrophils Standard Deviation 7.41	1.34 Percentage of neutrophils Standard Deviation 7.85

SECONDARY outcome

Timeframe: Week 0, week 26

Population: SAS included all participants who received at least one dose of IDegLira or IDeg. Number analyzed = participants with available data.

Calcitonin levels were measured and were categorised as low, normal or high. Number of participants in each category at week 0 and week 26 were presented.

Outcome measures

Measure	Insulin Degludec n=151 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=301 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Change in Calcitonin Week 0 · Normal	149 Participants	293 Participants
Change in Calcitonin Week 0 · Low	0 Participants	0 Participants
Change in Calcitonin Week 0 · High	2 Participants	8 Participants
Change in Calcitonin Week 26 · Low	0 Participants	0 Participants
Change in Calcitonin Week 26 · Normal	136 Participants	279 Participants
Change in Calcitonin Week 26 · High	3 Participants	10 Participants

SECONDARY outcome

Timeframe: Week 0, week 26

Population: SAS included all participants who received at least one dose of IDegLira or IDeg. Number analyzed = participants with available data.

The urinalysis was the measurements of protein, glucose, erythrocytes and ketones at week 0 and week 26 and categorised as negative, trace, 1+, 2+ and 3+. Number of participants in each category at week 0 and week 26 are presented.

Outcome measures

Measure	Insulin Degludec n=151 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=301 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Urinalysis (Erythrocytes, Protein, Glucose and Ketones) Week 0: Erythrocytes · Negative	121 Participants	258 Participants
Urinalysis (Erythrocytes, Protein, Glucose and Ketones) Week 0: Erythrocytes · Trace	22 Participants	33 Participants
Urinalysis (Erythrocytes, Protein, Glucose and Ketones) Week 0: Erythrocytes · 1+	4 Participants	3 Participants
Urinalysis (Erythrocytes, Protein, Glucose and Ketones) Week 0: Erythrocytes · 2+	3 Participants	2 Participants
Urinalysis (Erythrocytes, Protein, Glucose and Ketones) Week 0: Erythrocytes · 3+	1 Participants	4 Participants
Urinalysis (Erythrocytes, Protein, Glucose and Ketones) Week 26: Erythrocytes · Negative	120 Participants	255 Participants
Urinalysis (Erythrocytes, Protein, Glucose and Ketones) Week 26: Erythrocytes · Trace	11 Participants	22 Participants
Urinalysis (Erythrocytes, Protein, Glucose and Ketones) Week 26: Erythrocytes · 1+	1 Participants	6 Participants
Urinalysis (Erythrocytes, Protein, Glucose and Ketones) Week 26: Erythrocytes · 2+	4 Participants	2 Participants
Urinalysis (Erythrocytes, Protein, Glucose and Ketones) Week 26: Erythrocytes · 3+	3 Participants	2 Participants
Urinalysis (Erythrocytes, Protein, Glucose and Ketones) Week 0: Glucose · Negative	92 Participants	171 Participants
Urinalysis (Erythrocytes, Protein, Glucose and Ketones) Week 0: Glucose · Trace	13 Participants	33 Participants
Urinalysis (Erythrocytes, Protein, Glucose and Ketones) Week 0: Glucose · 1+	17 Participants	30 Participants
Urinalysis (Erythrocytes, Protein, Glucose and Ketones) Week 0: Glucose · 2+	13 Participants	25 Participants
Urinalysis (Erythrocytes, Protein, Glucose and Ketones) Week 0: Glucose · 3+	16 Participants	41 Participants
Urinalysis (Erythrocytes, Protein, Glucose and Ketones) Week 26: Glucose · Negative	110 Participants	256 Participants
Urinalysis (Erythrocytes, Protein, Glucose and Ketones) Week 26: Glucose · Trace	16 Participants	14 Participants
Urinalysis (Erythrocytes, Protein, Glucose and Ketones) Week 26: Glucose · 1+	9 Participants	10 Participants
Urinalysis (Erythrocytes, Protein, Glucose and Ketones) Week 26: Glucose · 2+	2 Participants	4 Participants
Urinalysis (Erythrocytes, Protein, Glucose and Ketones) Week 26: Glucose · 3+	2 Participants	3 Participants
Urinalysis (Erythrocytes, Protein, Glucose and Ketones) Week 0: Ketones · Negative	137 Participants	274 Participants
Urinalysis (Erythrocytes, Protein, Glucose and Ketones) Week 0: Ketones · Trace	10 Participants	21 Participants
Urinalysis (Erythrocytes, Protein, Glucose and Ketones) Week 0: Ketones · 1+	4 Participants	5 Participants
Urinalysis (Erythrocytes, Protein, Glucose and Ketones) Week 0: Ketones · 2+	0 Participants	0 Participants
Urinalysis (Erythrocytes, Protein, Glucose and Ketones) Week 0: Ketones · 3+	0 Participants	0 Participants
Urinalysis (Erythrocytes, Protein, Glucose and Ketones) Week 26: Ketones · Negative	132 Participants	272 Participants
Urinalysis (Erythrocytes, Protein, Glucose and Ketones) Week 26: Ketones · Trace	7 Participants	14 Participants
Urinalysis (Erythrocytes, Protein, Glucose and Ketones) Week 26: Ketones · 1+	0 Participants	1 Participants
Urinalysis (Erythrocytes, Protein, Glucose and Ketones) Week 26: Ketones · 2+	0 Participants	0 Participants
Urinalysis (Erythrocytes, Protein, Glucose and Ketones) Week 26: Ketones · 3+	0 Participants	0 Participants
Urinalysis (Erythrocytes, Protein, Glucose and Ketones) Week 0: Protein · Negative	89 Participants	172 Participants
Urinalysis (Erythrocytes, Protein, Glucose and Ketones) Week 0: Protein · Trace	32 Participants	72 Participants
Urinalysis (Erythrocytes, Protein, Glucose and Ketones) Week 0: Protein · 1+	18 Participants	36 Participants
Urinalysis (Erythrocytes, Protein, Glucose and Ketones) Week 0: Protein · 2+	10 Participants	16 Participants
Urinalysis (Erythrocytes, Protein, Glucose and Ketones) Week 0: Protein · 3+	2 Participants	4 Participants
Urinalysis (Erythrocytes, Protein, Glucose and Ketones) Week 26: Protein · Negative	89 Participants	198 Participants
Urinalysis (Erythrocytes, Protein, Glucose and Ketones) Week 26: Protein · Trace	22 Participants	47 Participants
Urinalysis (Erythrocytes, Protein, Glucose and Ketones) Week 26: Protein · 1+	18 Participants	29 Participants
Urinalysis (Erythrocytes, Protein, Glucose and Ketones) Week 26: Protein · 2+	9 Participants	11 Participants
Urinalysis (Erythrocytes, Protein, Glucose and Ketones) Week 26: Protein · 3+	1 Participants	2 Participants

SECONDARY outcome

Timeframe: Week 27

Population: SAS included all participants who received at least one dose of IDegLira or IDeg. Overall number of participants analyzed = participants with available data.

Serum samples were analysed for the presence of anti-insulin degludec specific antibodies. Results are presented as percentage of bound radioactivity-labelled insulin/total added radioactivity-labelled insulin (%B/T).

Outcome measures

Measure	Insulin Degludec n=143 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=288 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Anti-insulin Degludec Specific Antibodies	0.13 %B/T Standard Deviation 0.57	0.25 %B/T Standard Deviation 1.25

SECONDARY outcome

Timeframe: Week 27

Population: SAS included all participants who received at least one dose of IDegLira or IDeg. Overall number of participants analyzed = participants with available data.

Serum samples were analysed for the presence of antibodies cross-reacting to human insulin. Results are presented as percentage of bound radioactivity-labelled insulin/total added radioactivity-labelled insulin (%B/T).

Outcome measures

Measure	Insulin Degludec n=143 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=288 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Antibodies Cross-reacting to Human Insulin	8.64 %B/T Standard Deviation 16.84	9.07 %B/T Standard Deviation 16.61

SECONDARY outcome

Timeframe: Week 27

Population: SAS included all participants who received at least one dose of IDegLira or IDeg. Overall number of participants analyzed = participants with available data.

Serum samples were analysed for the presence of total insulin antibodies. Results are presented as percentage of bound radioactivity-labelled insulin/total added radioactivity-labelled insulin (%B/T).

Outcome measures

Measure	Insulin Degludec n=143 Participants Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=288 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Total Insulin Antibodies	8.77 %B/T Standard Deviation 17.19	9.31 %B/T Standard Deviation 17.33

SECONDARY outcome

Timeframe: Week 27

Population: SAS included all participants who received at least one dose of IDegLira or IDeg. Overall number of participants analyzed = participants with available data.

This outcome measure is only applicable for the Insulin degludec/liraglutide treatment arm. Number of participants who measured with anti-liraglutide antibodies at week 27 are presented.

Outcome measures

Measure	Insulin Degludec Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=288 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Occurrence of Anti-liraglutide Antibodies (Yes/no) Yes	—	24 Participants
Occurrence of Anti-liraglutide Antibodies (Yes/no) No	—	264 Participants

SECONDARY outcome

Timeframe: Week 27

Population: SAS included all participants who received at least one dose of IDegLira or IDeg. Overall number of participants analyzed = participants with available data.

This outcome measure is only applicable for the Insulin degludec/liraglutide treatment arm. Number of participants who measured with anti-liraglutide antibodies cross reacting native GLP-1 at week 27 are presented.

Outcome measures

Measure	Insulin Degludec Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=288 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Occurrence of Anti-liraglutide Antibodies Cross Reacting Native Glucagon-like Peptide-1 (GLP-1) Yes	—	6 Participants

SECONDARY outcome

Timeframe: Week 27

Population: SAS included all participants who received at least one dose of IDegLira or IDeg. Overall number of participants analyzed = participants with available data.

This outcome measure is only applicable for the Insulin degludec/liraglutide treatment arm. Number of participants who measured with neutralising liraglutide antibodies at week 27 are presented.

Outcome measures

Measure	Insulin Degludec Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=288 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Occurrence of Neutralising Liraglutide Antibodies Yes	—	0 Participants

SECONDARY outcome

Timeframe: Week 27

Population: SAS included all participants who received at least one dose of IDegLira or IDeg. Overall number of participants analyzed = participants with available data.

This outcome measure is only applicable for the Insulin degludec/liraglutide treatment arm. Number of participants who measured with neutralising liraglutide antibodies cross reacting native GLP-1 at week 27 are presented.

Outcome measures

Measure	Insulin Degludec Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.	Insulin Degludec/Liraglutide n=288 Participants Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.
Occurrence of Neutralising Liraglutide Antibodies Cross Reacting Native GLP-1 Yes	—	0 Participants

Adverse Events

Insulin Degludec/Liraglutide

Serious events: 13 serious events

Other events: 113 other events

Deaths: 0 deaths

Insulin Degludec

Serious events: 7 serious events

Other events: 43 other events

Deaths: 0 deaths

Serious adverse events

Measure	Insulin Degludec/Liraglutide n=301 participants at risk Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Insulin Degludec n=151 participants at risk Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.
Cardiac disorders Angina unstable	0.33% 1/301 • Number of events 1 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.	0.66% 1/151 • Number of events 1 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.
Eye disorders Cataract	0.33% 1/301 • Number of events 1 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.	0.00% 0/151 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.
Nervous system disorders Cerebral infarction	0.00% 0/301 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.	0.66% 1/151 • Number of events 1 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.
Gastrointestinal disorders Constipation	0.33% 1/301 • Number of events 1 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.	0.00% 0/151 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.
Cardiac disorders Coronary artery disease	0.00% 0/301 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.	1.3% 2/151 • Number of events 2 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.
Cardiac disorders Coronary artery stenosis	0.00% 0/301 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.	0.66% 1/151 • Number of events 1 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.
Gastrointestinal disorders Diarrhoea	0.33% 1/301 • Number of events 1 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.	0.00% 0/151 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.
Infections and infestations Epiglottitis	0.00% 0/301 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.	0.66% 1/151 • Number of events 1 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/301 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.	0.66% 1/151 • Number of events 1 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Fibroadenoma of breast	0.33% 1/301 • Number of events 1 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.	0.00% 0/151 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.
Nervous system disorders Hypoaesthesia	0.33% 1/301 • Number of events 1 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.	0.00% 0/151 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.
Musculoskeletal and connective tissue disorders Muscular weakness	0.33% 1/301 • Number of events 1 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.	0.00% 0/151 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.
Cardiac disorders Myocardial infarction	0.33% 1/301 • Number of events 1 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.	0.00% 0/151 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.
Musculoskeletal and connective tissue disorders Osteoporotic fracture	0.33% 1/301 • Number of events 1 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.	0.00% 0/151 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	0.33% 1/301 • Number of events 1 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.	0.00% 0/151 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.
Injury, poisoning and procedural complications Spinal compression fracture	0.33% 1/301 • Number of events 1 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.	0.00% 0/151 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.33% 1/301 • Number of events 1 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.	0.00% 0/151 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.
Congenital, familial and genetic disorders Thyroglossal cyst	0.33% 1/301 • Number of events 1 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.	0.00% 0/151 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.
Nervous system disorders Transient ischaemic attack	0.33% 1/301 • Number of events 1 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.	0.00% 0/151 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.
Gastrointestinal disorders Vomiting	0.33% 1/301 • Number of events 1 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.	0.00% 0/151 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.

Other adverse events

Measure	Insulin Degludec/Liraglutide n=301 participants at risk Participants were to receive Insulin degludec/liraglutide (IDegLira) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 dose steps (16 units insulin degludec and 0.6 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) values. The maximum dose was 50 dose steps (50 units IDeg/1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Insulin Degludec n=151 participants at risk Participants were to receive Insulin degludec (IDeg) subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 16 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG values. The maximum dose was 50 units IDeg.
Metabolism and nutrition disorders Decreased appetite	7.0% 21/301 • Number of events 23 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.	2.0% 3/151 • Number of events 3 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.
Eye disorders Diabetic retinopathy	11.6% 35/301 • Number of events 35 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.	7.3% 11/151 • Number of events 11 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.
Gastrointestinal disorders Diarrhoea	7.3% 22/301 • Number of events 30 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.	1.3% 2/151 • Number of events 2 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.
Investigations Lipase increased	12.0% 36/301 • Number of events 38 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.	2.0% 3/151 • Number of events 3 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.
Infections and infestations Upper respiratory tract infection	12.6% 38/301 • Number of events 45 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.	17.9% 27/151 • Number of events 32 • Weeks 0-30 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants who received at least one dose of IDegLira or IDeg.

Additional Information

Clinical Reporting Anchor and Disclosure (1452)

Novo Nordisk A/S

Phone: (+1) 866-867-7178

Email: clinicaltrials@novonordisk.com

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.
• Publication restrictions are in place

Restriction type: OTHER