DUAL™ II China: 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)

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03175120
• Collaborator: (none)
• Enrollment: 453
• Locations: 37
• Arms: 2
• Actual Duration (Months): 22.3
• Patients Per Site: 12.2
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This trial is conducted in Asia. The aim of this trial is to confirm the superiority of insulin degludec/liraglutide versus insulin degludec in controlling glycaemia in Chinese subjects with type 2 diabetes mellitus after 26 weeks of treatment

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 453 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Trial Comparing the Efficacy and Safety of 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 OAD
• Actual Study Start Date: May 26, 2017
• Actual Primary Completion Date: Mar 5, 2019
• Actual Study Completion Date: Apr 4, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Insulin degludec/liraglutide	Drug: Insulin degludec/liraglutide; Administered subcutaneously (s.c., under the skin) once daily in combination with metformin for the treatment duration of 26 weeks.
Active Comparator: Insulin degludec	Drug: Insulin degludec; Administered subcutaneously (s.c., under the skin) once daily in combination with metformin for the treatment duration of 26 weeks.

Outcome Measures

Primary Outcome Measures

1. Change in HbA1c [Week 0, week 26]

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

Secondary Outcome Measures

1. Change in Body Weight [Week 0, week 26]

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

2. Number of Treatment-emergent Severe or Blood Glucose (BG) Confirmed Hypoglycaemic Episodes [Up to 26 weeks]

   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.

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

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

4. Change in Waist Circumference [Week 0, week 26]

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

5. Change in Mean of the 9-point Self-measured Plasma Glucose (SMPG) Profile [Week 0, week 26]

   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.

6. Change in SMPG-mean Post Prandial Increments [Week 0, week 26]

   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.

7. Insulin Dose [Week 26]

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

8. SMPG-9-point Profile (Individual Points in the Profile) [Week 26]

   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.

9. Change in Fasting High-density Lipoprotein (HDL) Cholesterol- Ratio to Baseline [Week 0, week 26]

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

10. Change in Fasting Low-density Lipoprotein (LDL) Cholesterol- Ratio to Baseline [Week 0, week 26]

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

11. Change in Fasting Very Low-density Lipoprotein (VLDL) Cholesterol- Ratio to Baseline [Week 0, week 26]

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

12. Change in Fasting Total Cholesterol- Ratio to Baseline [Week 0, week 26]

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

13. Change in Fasting Triglycerides- Ratio to Baseline [Week 0, week 26]

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

14. Change in Fasting Free Fatty Acids- Ratio to Baseline [Week 0, week 26]

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

15. Change in Fasting C-peptide- Ratio to Baseline [Week 0, week 26]

    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.

16. Change in Fasting Insulin- Ratio to Baseline [Week 0, week 26]

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

17. Change in Fasting Glucagon- Ratio to Baseline [Week 0, week 26]

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

18. Change in HOMA-B (Beta-cell Function)- Ratio to Baseline [Week 0, week 26]

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

19. Participants Who Achieved HbA1c < 7.0%, ADA Target (Yes/no) [Week 26]

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

20. Participants Who Achieved HbA1c ≤ 6.5%, American Association of Clinical Endocrinologists (AACE) Target (Yes/no) [Week 26]

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

21. Participants Who Achieved HbA1c < 7.0% and Change From Baseline in Body Weight Below or Equal to Zero [Week 26]

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

22. Participants Who Achieved HbA1c ≤ 6.5% and Change From Baseline in Body Weight Below or Equal to Zero [Week 26]

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

23. Participants Who Achieved HbA1c < 7.0% Without Treatment-emergent Severe or BG Confirmed Hypoglycaemic Episodes [Week 26]

    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.

24. Participants Who Achieved HbA1c ≤ 6.5% Without Treatment-emergent Severe or BG Confirmed Hypoglycaemic Episodes [Week 26]

    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.

25. 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 [Week 26]

    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.

26. 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 [Week 26]

    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.

27. Number of Treatment-emergent Adverse Events (TEAEs) [Weeks 0-27]

    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.

28. Number of Treatment-emergent Nocturnal Severe or BG Confirmed Hypoglycaemic Episodes [Weeks 0-27]

    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.

29. Number of Treatment-emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes [Weeks 0-27]

    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.

30. Number of Treatment-emergent Nocturnal Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes [Weeks 0-27]

    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.

31. Number of Treatment-emergent Hypoglycaemic Episodes According to ADA Definition [Weeks 0-27]

    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.

32. Change in Physical Examination [Week -2, week 26]

    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.

33. Eye Examination [Week -2, week 26]

    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.

34. Change in Electrocardiogram (ECG) [Week -2, week 26]

    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.

35. Change in Pulse [Week 0, week 26]

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

36. Change in Blood Pressure (Systolic and Diastolic Blood Pressure) [Week 0, week 26]

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

37. Change in Biochemical Parameter- Amylase, Lipase, Creatinine Kinase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) [Week 0, week 26]

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

38. Change in Biochemical Parameter-calcium (Total), Albumin Corrected Calcium, Potassium, Sodium, Urea [Week 0, week 26]

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

39. Change in Albumin [Week 0, week 26]

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

40. Change in Total Bilirubin [Week 0, week 26]

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

41. Change in Creatinine [Week 0, week 26]

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

42. Change in Total Protein [Week 0, week 26]

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

43. Change in Haematological Parameter- Haematocrit [Week 0, week 26]

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

44. Change in Haematological Parameter- Haemoglobin [Week 0, week 26]

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

45. Change in Haematological Parameter- Leukocytes and Thrombocytes [Week 0, week 26]

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

46. Change in Haematological Parameter- Erythrocytes [Week 0, week 26]

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

47. Change in Haematological Parameter- Basophils [Week 0, week 26]

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

48. Change in Haematological Parameter- Eosinophils [Week 0, week 26]

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

49. Change in Haematological Parameter- Lymphocytes [Week 0, week 26]

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

50. Change in Haematological Parameter- Monocytes [Week 0, week 26]

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

51. Change in Haematological Parameter- Neutrophils [Week 0, week 26]

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

52. Change in Calcitonin [Week 0, week 26]

    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.

53. Urinalysis (Erythrocytes, Protein, Glucose and Ketones) [Week 0, week 26]

    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.

54. Anti-insulin Degludec Specific Antibodies [Week 27]

    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).

55. Antibodies Cross-reacting to Human Insulin [Week 27]

    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).

56. Total Insulin Antibodies [Week 27]

    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).

57. Occurrence of Anti-liraglutide Antibodies (Yes/no) [Week 27]

    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.

58. Occurrence of Anti-liraglutide Antibodies Cross Reacting Native Glucagon-like Peptide-1 (GLP-1) [Week 27]

    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.

59. Occurrence of Neutralising Liraglutide Antibodies [Week 27]

    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.

60. Occurrence of Neutralising Liraglutide Antibodies Cross Reacting Native GLP-1 [Week 27]

    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.

Eligibility Criteria

Criteria

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

Inclusion Criteria: Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including procedures to determine suitability for the trial - Male or female, age at least 18 years at the time of signing inform consent - Type 2 diabetes mellitus (clinically diagnosed) - HbA1c (glycosylated haemoglobin) above or equal to 7.5% by central laboratory analysis, with the aim of a median of 8.5%. When approximately 50% of the randomised subjects have an HbA1c above 8.5%, the remaining subjects randomised must have an HbA1c below or equal to 8.5% or when approximately 50% of the subjects randomised have an HbA1c below or equal to 8.5%, the remaining subjects randomised must have an HbA1c above 8.5% - Current treatment for at least 90 calendar days prior to screening with basal insulin plus metformin plus/minus α-glucosidase inhibitors, sulphonylureas, glinides or thiazolidinediones. Subjects should be on a stable dose for at least 60 calendar days prior to screening of: Basal insulin 20-50 units (U)/day (both inclusive) ( Individual fluctuations of plus/minus 5U during the 60 day period prior to the day of screening are acceptable.) on the day of screening in combination with: - Metformin (above or equal to 1500 mg or max tolerated dose) or - Metformin (above or equal to 1500 mg or max tolerated dose) and sulphonylureas (above or equal to half of the max approved dose according to local label) or - Metformin (above or equal to 1500 mg or max tolerated dose) and glinide (at least half of the max approved dose according to local label) or - Metformin (above or equal to 1500 mg or max tolerated dose) and α-glucosidase inhibitors (AGI) (at least half of the max approved dose according to local label) or - Metformin (above or equal to 1500 mg or max tolerated dose) and thiazolidinediones (at least half of the max approved dose according to local label) - Body mass index (BMI) above or equal to 24 kg/m^2 Exclusion Criteria: Current use of any antidiabetic drug (except for basal insulin, metformin, α-glucosidase inhibitors, sulphonylureas, glinides or thiazolidinediones) or anticipated change in concomitant medication, that in the investigator´s opinion could interfere with glucose level (e.g. systemic corticosteroids) - Treatment with glucagon like peptide -1 receptor agonists, or dipeptidyl-peptidase-4 inhibitors or insulin (except for basal insulin) within 90 days prior to Visit 1 - Impaired liver function defined as alanine aminotransferase above or equal to 2.5 times upper normal range - Impaired renal function defined as serum-creatinine above or equal to 133 μmol/L for males and above or equal to 125 μmol/L for females, or as defined according to local contraindications for metformin Screening calcitonin above or equal to 50 ng/L - Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN2) - Cardiac disorder defined as: congestive heart failure (NYHA class III-IV), diagnosis of unstable angina pectoris, cerebral stroke and/or myocardial infarction within the last 12 months prior to screening and/or planned coronary, carotid or peripheral artery revascularisation procedures - Severe uncontrolled treated or untreated hypertension (systolic blood pressure above or equal to 180 mm Hg or diastolic blood pressure above or equal to 100 mm Hg) - Proliferative retinopathy or maculopathy (macular oedema) requiring acute treatment - History of pancreatitis (acute or chronic)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Hefei	Anhui	China	230001
2	Novo Nordisk Investigational Site	Hefei	Anhui	China	230061
3	Novo Nordisk Investigational Site	Beijing	Beijing	China	100071
4	Novo Nordisk Investigational Site	Beijing	Beijing	China	100088
5	Novo Nordisk Investigational Site	Beijing	Beijing	China	100730
6	Novo Nordisk Investigational Site	Beijing	Beijing	China	100853
7	Novo Nordisk Investigational Site	ChongQing	Chongqing	China	404000
8	Novo Nordisk Investigational Site	Fuzhou	Fujian	China	350001
9	Novo Nordisk Investigational Site	Guangzhou	Guangdong	China	510120
10	Novo Nordisk Investigational Site	Guangzhou	Guangdong	China	510515
11	Novo Nordisk Investigational Site	Hengshui	Hebei	China	053000
12	Novo Nordisk Investigational Site	Shijiazhuang	Hebei	China	050000
13	Novo Nordisk Investigational Site	Tangshan	Hebei	China	063000
14	Novo Nordisk Investigational Site	Harbin	Heilongjiang	China	150001
15	Novo Nordisk Investigational Site	Yueyang	Hunan	China	414000
16	Novo Nordisk Investigational Site	Huhehaote	Inner Mongolia	China	010020
17	Novo Nordisk Investigational Site	Huhhot	Inner Mongolia	China	010050
18	Novo Nordisk Investigational Site	Changzhou	Jiangsu	China	213003
19	Novo Nordisk Investigational Site	Nanjing	Jiangsu	China	210011
20	Novo Nordisk Investigational Site	Nanjing	Jiangsu	China	210012
21	Novo Nordisk Investigational Site	Nanjing	Jiangsu	China	210029
22	Novo Nordisk Investigational Site	Zhenjiang	Jiangsu	China	212001
23	Novo Nordisk Investigational Site	Nanchang	Jiangxi	China	330006
24	Novo Nordisk Investigational Site	Changchun	Jilin	China	130021
25	Novo Nordisk Investigational Site	Changchun	Jilin	China	130033
26	Novo Nordisk Investigational Site	Siping	Jilin	China	136000
27	Novo Nordisk Investigational Site	Dalian	Liaoning	China	116011
28	Novo Nordisk Investigational Site	Yinchuan	Ningxia	China	750004
29	Novo Nordisk Investigational Site	Xi'an	Shaanxi	China	710061
30	Novo Nordisk Investigational Site	Shanghai	Shanghai	China	200040
31	Novo Nordisk Investigational Site	Shanghai	Shanghai	China	200072
32	Novo Nordisk Investigational Site	Shanghai	Shanghai	China	200240
33	Novo Nordisk Investigational Site	Shanghai	Shanghai	China	201199
34	Novo Nordisk Investigational Site	Taiyuan	Shanxi	China	030001
35	Novo Nordisk Investigational Site	Tianjin	Tianjin	China	300052
36	Novo Nordisk Investigational Site	Kunming	Yunnan	China	650101
37	Novo Nordisk Investigational Site	Shatin, New Territories		Hong Kong

Sponsors and Collaborators

• Novo Nordisk A/S

Investigators

• Study Director: Global Clinical Registry (GCR,1452), Novo Nordisk A/S

Study Documents (Full-Text)

• Statistical Analysis Plan - Jan 23, 2020
• Study Protocol - Dec 4, 2019

More Information

Publications

None provided.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT03175120
• Other Study ID Numbers: NN9068-4166; U1111-1154-6732; CTR20060909
• First Posted: Jun 5, 2017
• Last Update Posted: Mar 19, 2020
• Last Verified: Mar 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Insulin; Insulin, Globin Zinc; Liraglutide; Insulin, Long-Acting; Xultophy

Study Results

Participant Flow

Recruitment Details	The trial was conducted at 40 sites in China.
Pre-assignment Detail	Participants were randomised in a 2:1 manner to receive either IDegLira or IDeg in combination with metformin.

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Period Title: Overall Study
STARTED	302	151
Treated	301	151
Full Analysis Set (FAS)	302	151
Safety Analysis Set (SAS)	301	151
COMPLETED	290	139
NOT COMPLETED	12	12

Baseline Characteristics

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Total
Arm/Group Description	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 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 of all reporting groups
Overall Participants	302	151	453
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	54.5 (9.8)	55.3 (10.0)	54.7 (9.9)
Sex: Female, Male (Count of Participants)
Female	119 39.4%	60 39.7%	179 39.5%
Male	183 60.6%	91 60.3%	274 60.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	302 100%	151 100%	453 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	302 100%	151 100%	453 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Glycosylated haemoglobin (HbA1c) (Percentage of HbA1c) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percentage of HbA1c]	8.93 (1.20)	8.96 (1.17)	8.94 (1.19)

Outcome Measures

1. Primary Outcome

Title	Change in HbA1c
Description	Change in glycosylated haemoglobin (HbA1c) from baseline (week 0) to week 26 is presented.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	289	138
Mean (Standard Deviation) [Percentage point of HbA1c]	-1.93 (1.14)	-1.06 (1.19)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Degludec/Liraglutide, Insulin Degludec
	Comments	The response and change from baseline in response after 26 weeks are analysed using an analysis of covariance (ANCOVA) model with treatment and previous anti-diabetic treatment as fixed factors and corresponding baseline value as covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment contrast
	Estimated Value	-0.92
	Confidence Interval	(2-Sided) 95%; -1.09 to -0.75
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change in Body Weight
Description	Change in body weight from baseline (week 0) to week 26 is presented.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	288	139
Mean (Standard Deviation) [Kilogram (kg)]	-0.7 (3.0)	0.5 (2.7)

3. Secondary Outcome

Title	Number of Treatment-emergent Severe or Blood Glucose (BG) Confirmed Hypoglycaemic Episodes
Description	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.
Time Frame	Up to 26 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	301	151
Number [Episodes]	38	36

4. Secondary Outcome

Title	Change in Fasting Plasma Glucose (FPG)
Description	Change in FPG from baseline (week 0) to week 26 is presented.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	289	139
Mean (Standard Deviation) [mmol/L]	-3.57 (3.00)	-2.82 (3.15)

5. Secondary Outcome

Title	Change in Waist Circumference
Description	Change in waist circumference from baseline (week 0) to week 26 is presented.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	288	139
Mean (Standard Deviation) [Centimeter (cm)]	-0.4 (4.3)	0.7 (3.3)

6. Secondary Outcome

Title	Change in Mean of the 9-point Self-measured Plasma Glucose (SMPG) Profile
Description	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.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	272	133
Mean (Standard Deviation) [mmol/L]	-3.35 (2.63)	-2.31 (2.61)

7. Secondary Outcome

Title	Change in SMPG-mean Post Prandial Increments
Description	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.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	280	134
Mean (Standard Deviation) [mmol/L]	0.08 (2.19)	0.28 (2.71)

8. Secondary Outcome

Title	Insulin Dose
Description	The mean of actual daily total insulin dose after 26 weeks of treatment is presented.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	290	139
Mean (Standard Deviation) [Units of insulin (U)]	34.6 (11.1)	37.9 (10.8)

9. Secondary Outcome

Title	SMPG-9-point Profile (Individual Points in the Profile)
Description	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.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	302	151
Before breakfast	5.48 (1.06)	5.88 (1.30)
90 minutes after start of breakfast	9.51 (2.66)	10.50 (2.45)
Before lunch	6.93 (2.10)	8.17 (3.19)
90 minutes after start of lunch	9.68 (2.52)	11.21 (2.93)
Before main evening meal	7.24 (2.16)	7.87 (2.65)
90 minutes after main evening meal	9.87 (2.53)	10.86 (2.46)
At bedtime	8.57 (2.52)	9.52 (2.61)
At 4:00 a.m.	5.97 (1.49)	6.61 (1.99)
Before breakfast the following day	5.48 (1.14)	5.83 (1.52)

10. Secondary Outcome

Title	Change in Fasting High-density Lipoprotein (HDL) Cholesterol- Ratio to Baseline
Description	Change in fasting HDL cholesterol (measured in mmol/L) from baseline (week 0) to week 26 is presented as ratio to baseline.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	289	139
Geometric Mean (Geometric Coefficient of Variation) [Ratio of HDL cholesterol]	1.00 (17.5)	1.03 (15.9)

11. Secondary Outcome

Title	Change in Fasting Low-density Lipoprotein (LDL) Cholesterol- Ratio to Baseline
Description	Change in fasting LDL cholesterol (measured in mmol/L) from baseline (week 0) to week 26 is presented as ratio to baseline.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	284	134
Geometric Mean (Geometric Coefficient of Variation) [Ratio of LDL cholesterol]	0.89 (32.5)	0.95 (37.7)

12. Secondary Outcome

Title	Change in Fasting Very Low-density Lipoprotein (VLDL) Cholesterol- Ratio to Baseline
Description	Change in fasting VLDL cholesterol (measured in mmol/L) from baseline (week 0) to week 26 is presented as ratio to baseline.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	289	139
Geometric Mean (Geometric Coefficient of Variation) [Ratio of VLDL cholesterol]	0.92 (55.2)	0.93 (49.1)

13. Secondary Outcome

Title	Change in Fasting Total Cholesterol- Ratio to Baseline
Description	Change in fasting total cholesterol (measured in mmol/L) from baseline (week 0) to week 26 is presented as ratio to baseline.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	289	139
Geometric Mean (Geometric Coefficient of Variation) [Ratio of total cholesterol]	0.92 (19.1)	0.97 (20.0)

14. Secondary Outcome

Title	Change in Fasting Triglycerides- Ratio to Baseline
Description	Change in fasting triglycerides (measured in mmol/L) from baseline (week 0) to week 26 is presented as ratio to baseline.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	289	139
Geometric Mean (Geometric Coefficient of Variation) [Ratio of triglycerides]	0.91 (63.7)	0.92 (55.8)

15. Secondary Outcome

Title	Change in Fasting Free Fatty Acids- Ratio to Baseline
Description	Change in fasting free fatty acids (measured in mmol/L) from baseline (week 0) to week 26 is presented as ratio to baseline.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	289	138
Geometric Mean (Geometric Coefficient of Variation) [Ratio of free fatty acids]	0.65 (76.4)	0.64 (61.9)

16. Secondary Outcome

Title	Change in Fasting C-peptide- Ratio to Baseline
Description	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.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	286	137
Geometric Mean (Geometric Coefficient of Variation) [Ratio of C-peptide]	0.64 (71.2)	0.52 (71.8)

17. Secondary Outcome

Title	Change in Fasting Insulin- Ratio to Baseline
Description	Change in fasting insulin (measured in picomoles per liter (pmol/L)) from baseline (week 0) to week 26 is presented as ratio to baseline.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	288	139
Geometric Mean (Geometric Coefficient of Variation) [Ratio of insulin]	0.63 (118.3)	0.50 (106.4)

18. Secondary Outcome

Title	Change in Fasting Glucagon- Ratio to Baseline
Description	Change in fasting glucagon (measured in picograms per milliliter (pg/mL)) from baseline (week 0) to week 26 is presented as ratio to baseline.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	287	138
Geometric Mean (Geometric Coefficient of Variation) [Ratio of glucagon]	1.01 (95.8)	1.09 (81.7)

19. Secondary Outcome

Title	Change in HOMA-B (Beta-cell Function)- Ratio to Baseline
Description	Change in HOMA-B from baseline (week 0) to week 26 is presented as ratio to baseline.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	287	139
Geometric Mean (Geometric Coefficient of Variation) [Ratio of beta-cell function]	1.47 (115.0)	0.99 (113.4)

20. Secondary Outcome

Title	Participants Who Achieved HbA1c < 7.0%, ADA Target (Yes/no)
Description	Participants who achieved HbA1c < 7.0%, ADA target (yes/no) is presented.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	289	138
Yes	151 50%	23 15.2%
No	138 45.7%	115 76.2%

21. Secondary Outcome

Title	Participants Who Achieved HbA1c ≤ 6.5%, American Association of Clinical Endocrinologists (AACE) Target (Yes/no)
Description	Participants who achieved HbA1c ≤ 6.5%, AACE target (yes/no) is presented.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	289	138
Yes	96 31.8%	10 6.6%
No	193 63.9%	128 84.8%

22. Secondary Outcome

Title	Participants Who Achieved HbA1c < 7.0% and Change From Baseline in Body Weight Below or Equal to Zero
Description	Participants who achieved HbA1c < 7.0% and change from baseline in body weight below or equal to zero is presented.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	302	151
Yes	98 32.5%	7 4.6%
No	204 67.5%	144 95.4%

23. Secondary Outcome

Title	Participants Who Achieved HbA1c ≤ 6.5% and Change From Baseline in Body Weight Below or Equal to Zero
Description	Participants who achieved HbA1c ≤ 6.5% and change from baseline in body weight below or equal to zero is presented.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	302	151
Yes	59 19.5%	3 2%
No	243 80.5%	148 98%

24. Secondary Outcome

Title	Participants Who Achieved HbA1c < 7.0% Without Treatment-emergent Severe or BG Confirmed Hypoglycaemic Episodes
Description	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.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	302	151
Yes	148 49%	22 14.6%
No	154 51%	129 85.4%

25. Secondary Outcome

Title	Participants Who Achieved HbA1c ≤ 6.5% Without Treatment-emergent Severe or BG Confirmed Hypoglycaemic Episodes
Description	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.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	302	151
Yes	93 30.8%	9 6%
No	209 69.2%	142 94%

26. Secondary Outcome

Title	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
Description	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.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	302	151
Yes	94 31.1%	7 4.6%
No	208 68.9%	144 95.4%

27. Secondary Outcome

Title	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
Description	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.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	302	151
Yes	58 19.2%	3 2%
No	244 80.8%	148 98%

28. Secondary Outcome

Title	Number of Treatment-emergent Adverse Events (TEAEs)
Description	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.
Time Frame	Weeks 0-27

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	301	151
Number [Adverse events]	641	230

29. Secondary Outcome

Title	Number of Treatment-emergent Nocturnal Severe or BG Confirmed Hypoglycaemic Episodes
Description	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.
Time Frame	Weeks 0-27

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	301	151
Number [Episodes]	9	8

30. Secondary Outcome

Title	Number of Treatment-emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes
Description	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.
Time Frame	Weeks 0-27

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	301	151
Number [Episodes]	23	21

31. Secondary Outcome

Title	Number of Treatment-emergent Nocturnal Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes
Description	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.
Time Frame	Weeks 0-27

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	301	151
Number [Episodes]	7	7

32. Secondary Outcome

Title	Number of Treatment-emergent Hypoglycaemic Episodes According to ADA Definition
Description	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.
Time Frame	Weeks 0-27

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	301	151
Number [Episodes]	1099	680

33. Secondary Outcome

Title	Change in Physical Examination
Description	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.
Time Frame	Week -2, week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	301	151
Normal	299 99%	149 98.7%
Abnormal NCS	1 0.3%	0 0%
Abnormal CS	1 0.3%	2 1.3%
Normal	286 94.7%	137 90.7%
Abnormal NCS	1 0.3%	0 0%
Abnormal CS	1 0.3%	2 1.3%
Normal	299 99%	150 99.3%
Abnormal NCS	2 0.7%	0 0%
Abnormal CS	0 0%	1 0.7%
Normal	287 95%	139 92.1%
Abnormal NCS	1 0.3%	0 0%
Abnormal CS	0 0%	0 0%
Normal	299 99%	150 99.3%
Abnormal NCS	2 0.7%	1 0.7%
Abnormal CS	0 0%	0 0%
Normal	285 94.4%	139 92.1%
Abnormal NCS	2 0.7%	0 0%
Abnormal CS	1 0.3%	0 0%
Normal	283 93.7%	141 93.4%
Abnormal NCS	11 3.6%	2 1.3%
Abnormal CS	7 2.3%	8 5.3%
Normal	273 90.4%	130 86.1%
Abnormal NCS	9 3%	2 1.3%
Abnormal CS	6 2%	7 4.6%
Normal	295 97.7%	147 97.4%
Abnormal NCS	2 0.7%	2 1.3%
Abnormal CS	4 1.3%	2 1.3%
Normal	283 93.7%	137 90.7%
Abnormal NCS	2 0.7%	1 0.7%
Abnormal CS	3 1%	1 0.7%
Normal	301 99.7%	151 100%
Abnormal NCS	0 0%	0 0%
Abnormal CS	0 0%	0 0%
Normal	288 95.4%	139 92.1%
Abnormal NCS	0 0%	0 0%
Abnormal CS	0 0%	0 0%
Normal	296 98%	145 96%
Abnormal NCS	2 0.7%	3 2%
Abnormal CS	3 1%	3 2%
Normal	280 92.7%	137 90.7%
Abnormal NCS	3 1%	1 0.7%
Abnormal CS	5 1.7%	1 0.7%
Normal	301 99.7%	151 100%
Abnormal NCS	0 0%	0 0%
Abnormal CS	0 0%	0 0%
Normal	288 95.4%	139 92.1%
Abnormal NCS	0 0%	0 0%
Abnormal CS	0 0%	0 0%
Normal	270 89.4%	132 87.4%
Abnormal NCS	22 7.3%	13 8.6%
Abnormal CS	9 3%	6 4%
Normal	259 85.8%	126 83.4%
Abnormal NCS	22 7.3%	9 6%
Abnormal CS	7 2.3%	4 2.6%
Normal	295 97.7%	147 97.4%
Abnormal NCS	4 1.3%	2 1.3%
Abnormal CS	2 0.7%	2 1.3%
Normal	284 94%	134 88.7%
Abnormal NCS	3 1%	3 2%
Abnormal CS	1 0.3%	2 1.3%

34. Secondary Outcome

Title	Eye Examination
Description	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.
Time Frame	Week -2, week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	301	151
Normal	167 55.3%	87 57.6%
Abnormal NCS	34 11.3%	15 9.9%
Abnormal CS	100 33.1%	49 32.5%
Normal	147 48.7%	80 53%
Abnormal NCS	35 11.6%	14 9.3%
Abnormal CS	105 34.8%	45 29.8%
Normal	162 53.6%	85 56.3%
Abnormal NCS	41 13.6%	18 11.9%
Abnormal CS	98 32.5%	47 31.1%
Normal	139 46%	84 55.6%
Abnormal NCS	37 12.3%	12 7.9%
Abnormal CS	111 36.8%	42 27.8%

35. Secondary Outcome

Title	Change in Electrocardiogram (ECG)
Description	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.
Time Frame	Week -2, week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	301	151
Normal	175 57.9%	90 59.6%
Abnormal NCS	76 25.2%	41 27.2%
Abnormal CS	50 16.6%	20 13.2%
Normal	175 57.9%	91 60.3%
Abnormal NCS	73 24.2%	32 21.2%
Abnormal CS	39 12.9%	16 10.6%

36. Secondary Outcome

Title	Change in Pulse
Description	Change in pulse from baseline (week 0) to week 26 is presented.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	288	139
Mean (Standard Deviation) [Beats per minute (beats/min)]	5.7 (9.6)	1.3 (8.7)

37. Secondary Outcome

Title	Change in Blood Pressure (Systolic and Diastolic Blood Pressure)
Description	Change in blood pressure (systolic and diastolic blood pressure) from baseline (week 0) to week 26 is presented.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	288	139
Systolic blood pressure	-3.5 (13.6)	-0.5 (12.5)
Diastolic blood pressure	0.1 (7.8)	-0.4 (8.1)

38. Secondary Outcome

Title	Change in Biochemical Parameter- Amylase, Lipase, Creatinine Kinase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP)
Description	Change in amylase, lipase, creatinine kinase, ALT, AST, ALP from baseline (week 0) to week 26 is presented.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	289	139
Amylase	10.45 (23.14)	2.69 (11.72)
Lipase	16.97 (35.24)	-0.35 (13.81)
Creatinine kinase	3.32 (65.17)	6.99 (84.31)
ALT	-3.02 (12.03)	-4.06 (11.97)
AST	-1.42 (7.46)	-2.06 (7.92)
ALP	-1.62 (13.30)	-1.70 (11.39)

39. Secondary Outcome

Title	Change in Biochemical Parameter-calcium (Total), Albumin Corrected Calcium, Potassium, Sodium, Urea
Description	Change in calcium (total), albumin corrected calcium, potassium, sodium, urea from baseline (week 0) to week 26 is presented.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	289	139
Calcium (total)	0.01 (0.10)	-0.01 (0.09)
Albumin corrected calcium	-0.00 (0.08)	-0.01 (0.08)
Potassium	-0.03 (0.34)	-0.11 (0.35)
Sodium	1.03 (2.47)	1.40 (2.43)
Urea	-0.09 (1.32)	0.17 (1.29)

40. Secondary Outcome

Title	Change in Albumin
Description	Change in albumin from baseline (week 0) to week 26 is presented.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	288	139
Mean (Standard Deviation) [Grams per deciliter (g/dL)]	0.05 (0.29)	0.02 (0.25)

41. Secondary Outcome

Title	Change in Total Bilirubin
Description	Change in total bilirubin from baseline (week 0) to week 26 is presented.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	289	139
Mean (Standard Deviation) [Micromoles per liter (umol/L)]	-0.30 (3.89)	-0.54 (3.66)

42. Secondary Outcome

Title	Change in Creatinine
Description	Change in creatinine from baseline (week 0) to week 26 is presented.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	289	139
Mean (Standard Deviation) [umol/L]	0.44 (7.93)	-0.32 (7.52)

43. Secondary Outcome

Title	Change in Total Protein
Description	Change in total protein from baseline (week 0) to week 26 is presented.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	289	139
Mean (Standard Deviation) [g/dL]	0.08 (0.41)	0.03 (0.39)

44. Secondary Outcome

Title	Change in Haematological Parameter- Haematocrit
Description	Change in haematocrit from baseline (week 0) to week 26 is presented.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	289	139
Mean (Standard Deviation) [Percentage of red blood cells]	-0.07 (2.56)	-0.12 (2.14)

45. Secondary Outcome

Title	Change in Haematological Parameter- Haemoglobin
Description	Change in haemoglobin from baseline (week 0) to week 26 is presented.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	288	139
Mean (Standard Deviation) [mmol/L]	-0.08 (0.52)	-0.09 (0.41)

46. Secondary Outcome

Title	Change in Haematological Parameter- Leukocytes and Thrombocytes
Description	Change in leukocytes and thrombocytes from baseline (week 0) to week 26 is presented.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	289	138
Leukocytes	0.32 (1.39)	0.31 (1.18)
Thrombocytes	14.13 (34.34)	12.19 (34.01)

47. Secondary Outcome

Title	Change in Haematological Parameter- Erythrocytes
Description	Change in erythrocytes from baseline (week 0) to week 26 is presented.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	289	139
Mean (Standard Deviation) [10^12 cells per liter (10^12/L)]	-0.06 (0.26)	-0.05 (0.24)

48. Secondary Outcome

Title	Change in Haematological Parameter- Basophils
Description	Change in basophils from baseline (week 0) to week 26 is presented.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	289	138
Mean (Standard Deviation) [Percentage of basophils]	0.00 (0.34)	0.01 (0.27)

49. Secondary Outcome

Title	Change in Haematological Parameter- Eosinophils
Description	Change in eosinophils from baseline (week 0) to week 26 is presented.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	289	138
Mean (Standard Deviation) [Percentage of eosinophils]	-0.15 (1.84)	-0.25 (1.72)

50. Secondary Outcome

Title	Change in Haematological Parameter- Lymphocytes
Description	Change in lymphocytes from baseline (week 0) to week 26 is presented.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	289	138
Mean (Standard Deviation) [Percentage of lymphocytes]	-1.00 (6.95)	-0.82 (6.41)

51. Secondary Outcome

Title	Change in Haematological Parameter- Monocytes
Description	Change in monocytes from baseline (week 0) to week 26 is presented.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	289	138
Mean (Standard Deviation) [Percentage of monocytes]	-0.19 (2.02)	-0.06 (2.19)

52. Secondary Outcome

Title	Change in Haematological Parameter- Neutrophils
Description	Change in neutrophils from baseline (week 0) to week 26 is presented.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	289	138
Mean (Standard Deviation) [Percentage of neutrophils]	1.34 (7.85)	0.99 (7.41)

53. Secondary Outcome

Title	Change in Calcitonin
Description	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.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	301	151
Low	0 0%	0 0%
Normal	293 97%	149 98.7%
High	8 2.6%	2 1.3%
Low	0 0%	0 0%
Normal	279 92.4%	136 90.1%
High	10 3.3%	3 2%

54. Secondary Outcome

Title	Urinalysis (Erythrocytes, Protein, Glucose and Ketones)
Description	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.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	301	151
Negative	258 85.4%	121 80.1%
Trace	33 10.9%	22 14.6%
1+	3 1%	4 2.6%
2+	2 0.7%	3 2%
3+	4 1.3%	1 0.7%
Negative	255 84.4%	120 79.5%
Trace	22 7.3%	11 7.3%
1+	6 2%	1 0.7%
2+	2 0.7%	4 2.6%
3+	2 0.7%	3 2%
Negative	171 56.6%	92 60.9%
Trace	33 10.9%	13 8.6%
1+	30 9.9%	17 11.3%
2+	25 8.3%	13 8.6%
3+	41 13.6%	16 10.6%
Negative	256 84.8%	110 72.8%
Trace	14 4.6%	16 10.6%
1+	10 3.3%	9 6%
2+	4 1.3%	2 1.3%
3+	3 1%	2 1.3%
Negative	274 90.7%	137 90.7%
Trace	21 7%	10 6.6%
1+	5 1.7%	4 2.6%
2+	0 0%	0 0%
3+	0 0%	0 0%
Negative	272 90.1%	132 87.4%
Trace	14 4.6%	7 4.6%
1+	1 0.3%	0 0%
2+	0 0%	0 0%
3+	0 0%	0 0%
Negative	172 57%	89 58.9%
Trace	72 23.8%	32 21.2%
1+	36 11.9%	18 11.9%
2+	16 5.3%	10 6.6%
3+	4 1.3%	2 1.3%
Negative	198 65.6%	89 58.9%
Trace	47 15.6%	22 14.6%
1+	29 9.6%	18 11.9%
2+	11 3.6%	9 6%
3+	2 0.7%	1 0.7%

55. Secondary Outcome

Title	Anti-insulin Degludec Specific Antibodies
Description	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).
Time Frame	Week 27

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	288	143
Mean (Standard Deviation) [%B/T]	0.25 (1.25)	0.13 (0.57)

56. Secondary Outcome

Title	Antibodies Cross-reacting to Human Insulin
Description	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).
Time Frame	Week 27

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	288	143
Mean (Standard Deviation) [%B/T]	9.07 (16.61)	8.64 (16.84)

57. Secondary Outcome

Title	Total Insulin Antibodies
Description	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).
Time Frame	Week 27

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	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 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.
Measure Participants	288	143
Mean (Standard Deviation) [%B/T]	9.31 (17.33)	8.77 (17.19)

58. Secondary Outcome

Title	Occurrence of Anti-liraglutide Antibodies (Yes/no)
Description	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.
Time Frame	Week 27

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide
Arm/Group Description	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.
Measure Participants	288
Yes	24 7.9%
No	264 87.4%

59. Secondary Outcome

Title	Occurrence of Anti-liraglutide Antibodies Cross Reacting Native Glucagon-like Peptide-1 (GLP-1)
Description	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.
Time Frame	Week 27

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide
Arm/Group Description	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.
Measure Participants	288
Yes	6 2%

60. Secondary Outcome

Title	Occurrence of Neutralising Liraglutide Antibodies
Description	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.
Time Frame	Week 27

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide
Arm/Group Description	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.
Measure Participants	288
Yes	0 0%

61. Secondary Outcome

Title	Occurrence of Neutralising Liraglutide Antibodies Cross Reacting Native GLP-1
Description	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.
Time Frame	Week 27

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide
Arm/Group Description	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.
Measure Participants	288
Yes	0 0%

Adverse Events

Time Frame	Weeks 0-30
Adverse Event Reporting Description	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.
Arm/Group Title	Insulin Degludec/Liraglutide		Insulin Degludec
Arm/Group Description	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 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.
All Cause Mortality
	Insulin Degludec/Liraglutide		Insulin Degludec
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/301 (0%)		0/151 (0%)
Serious Adverse Events
	Insulin Degludec/Liraglutide		Insulin Degludec
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/301 (4.3%)		7/151 (4.6%)
Cardiac disorders
Angina unstable	1/301 (0.3%)	1	1/151 (0.7%)	1
Coronary artery disease	0/301 (0%)	0	2/151 (1.3%)	2
Coronary artery stenosis	0/301 (0%)	0	1/151 (0.7%)	1
Myocardial infarction	1/301 (0.3%)	1	0/151 (0%)	0
Congenital, familial and genetic disorders
Thyroglossal cyst	1/301 (0.3%)	1	0/151 (0%)	0
Eye disorders
Cataract	1/301 (0.3%)	1	0/151 (0%)	0
Gastrointestinal disorders
Constipation	1/301 (0.3%)	1	0/151 (0%)	0
Diarrhoea	1/301 (0.3%)	1	0/151 (0%)	0
Vomiting	1/301 (0.3%)	1	0/151 (0%)	0
Infections and infestations
Epiglottitis	0/301 (0%)	0	1/151 (0.7%)	1
Injury, poisoning and procedural complications
Femur fracture	0/301 (0%)	0	1/151 (0.7%)	1
Spinal compression fracture	1/301 (0.3%)	1	0/151 (0%)	0
Musculoskeletal and connective tissue disorders
Muscular weakness	1/301 (0.3%)	1	0/151 (0%)	0
Osteoporotic fracture	1/301 (0.3%)	1	0/151 (0%)	0
Rotator cuff syndrome	1/301 (0.3%)	1	0/151 (0%)	0
Spinal osteoarthritis	1/301 (0.3%)	1	0/151 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Fibroadenoma of breast	1/301 (0.3%)	1	0/151 (0%)	0
Nervous system disorders
Cerebral infarction	0/301 (0%)	0	1/151 (0.7%)	1
Hypoaesthesia	1/301 (0.3%)	1	0/151 (0%)	0
Transient ischaemic attack	1/301 (0.3%)	1	0/151 (0%)	0
Other (Not Including Serious) Adverse Events
	Insulin Degludec/Liraglutide		Insulin Degludec
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	113/301 (37.5%)		43/151 (28.5%)
Eye disorders
Diabetic retinopathy	35/301 (11.6%)	35	11/151 (7.3%)	11
Gastrointestinal disorders
Diarrhoea	22/301 (7.3%)	30	2/151 (1.3%)	2
Infections and infestations
Upper respiratory tract infection	38/301 (12.6%)	45	27/151 (17.9%)	32
Investigations
Lipase increased	36/301 (12%)	38	3/151 (2%)	3
Metabolism and nutrition disorders
Decreased appetite	21/301 (7%)	23	3/151 (2%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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