DUAL™ I China: A Trial Comparing Insulin Degludec/Liraglutide, Insulin Degludec, and Liraglutide in Chinese Subjects With Type 2 Diabetes Inadequately Controlled on Oral Antidiabetic Drugs (OADs)

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03172494
• Collaborator: (none)
• Enrollment: 720
• Locations: 37
• Arms: 3
• Actual Duration (Months): 25.6
• Patients Per Site: 19.5
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

This trial is conducted in Asia. The aim of this trial is to confirm the efficacy of insulin degludec/liraglutide in controlling glycaemia in Chinese subjects with type 2 diabetes mellitus inadequately controlled on oral antidiabetic agents

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 720 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Trial Comparing the Efficacy and Safety of Insulin Degludec/Liraglutide, Insulin Degludec, and Liraglutide in Chinese Subjects With Type 2 Diabetes Inadequately Controlled on Oral Antidiabetic Drugs (OADs)
• Actual Study Start Date: May 26, 2017
• Actual Primary Completion Date: Jun 14, 2019
• Actual Study Completion Date: Jul 13, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Insulin degludec/liraglutide	Drug: Insulin degludec/liraglutide; Subcutaneously (s.c., under the skin)administration once daily in combination with metformin. For 26 weeks.
Active Comparator: Insulin degludec	Drug: Insulin degludec; Subcutaneously (s.c., under the skin)administration once daily in combination with metformin. For 26 weeks.
Active Comparator: Liraglutide	Drug: Liraglutide; Subcutaneously (s.c., under the skin)administration once daily in combination with metformin. For 26 weeks.

Outcome Measures

Primary Outcome Measures

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

   Change in HbA1c from baseline (week 0) after 26 weeks of treatment is presented.

Secondary Outcome Measures

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

   Change in body weight from baseline (week 0) after 26 weeks of treatment is presented.

2. Number of Treatment Emergent Severe or BG Confirmed Hypoglycaemic Episodes [Weeks 0-26]

   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 blood glucose (BG) confirmed by a plasma glucose (PG) 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. The number of episodes are represented as rates. The observed rates of treatment-emergent severe or BG confirmed hypoglycaemic episodes per patient years of exposure (PYE) (number of episodes divided by PYE multiplied by 100) during 26 weeks of treatment are presented.

3. Insulin Dose [Week 26]

   The actual daily total insulin dose after 26 weeks of treatment is presented. This outcome measure is only applicable for Insulin degludec/liraglutide and Insulin degludec treatment arms.

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

   Number of participants who achieved ADA HbA1c target (HbA1c < 7.0%) (yes/no) after 26 weeks of treatment are presented.

5. Participants Who Achieved HbA1c ≤ 6.5%, International Diabetes Federation (IDF) Target (Yes/no) [Week 26]

   Number of participants who achieved IDF HbA1c target (HbA1c ≤ 6.5%) (yes/no) after 26 weeks of treatment are presented.

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

   Number of participants who achieved ADA HbA1c target (HbA1c < 7.0%) (yes/no) and change from baseline in body weight below or equal to zero after 26 weeks are presented. Missing values are imputed by LOCF.

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

   Number of participants who achieved IDF HbA1c target (HbA1c ≤ 6.5%) (yes/no) and change from baseline in body weight below or equal to zero after 26 weeks are presented. Missing values are imputed by LOCF.

8. Participants Who Achieved HbA1c < 7.0% Without Severe or Blood Glucose (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 PG 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. Number of participants who achieved ADA HbA1c target (HbA1c <7.0%) (yes/no) after 26 weeks of treatment and without severe or BG confirmed hypoglycaemic episodes during the last 12 weeks of treatment are presented. Missing values are imputed by LOCF.

9. Participants Who Achieved HbA1c ≤ 6.5% Without 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 PG 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. Number of participants who achieved IDF HbA1c target (HbA1c ≤ 6.5%) (yes/no) after 26 weeks of treatment and without severe or BG confirmed hypoglycaemic episodes during the last 12 weeks of treatment are presented. Missing values are imputed by LOCF.

10. Participants Who Achieved HbA1c < 7.0% Without Severe or BG Confirmed Episodes, and Change From Baseline in Body Weight Below or Equal to Zero. [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 PG 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. Number of participants who achieved ADA HbA1c target (HbA1c < 7.0%) (yes/no) after 26 weeks of treatment without severe or BG confirmed hypoglycaemic episodes during the last 12 weeks of treatment and with change from baseline in body weight below or equal to zero are presented. Missing values are imputed by LOCF.

11. Participants Who Achieved HbA1c ≤ 6.5% Without Severe or BG Confirmed Episodes and Change From Baseline in Body Weight Below or Equal to Zero. [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 PG 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. Number of participants who achieved IDF HbA1c target (HbA1c ≤ 6.5%) (yes/no) after 26 weeks of treatment without severe or BG confirmed hypoglycaemic episodes during the last 12 weeks of treatment and with change from baseline in body weight below or equal to zero are presented. Missing values are imputed by LOCF.

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

    Change from baseline (week 0) in FPG after 26 weeks of treatment is presented.

13. Change in Waist Circumferance [Week 0, week 26]

    Change from baseline (week 0) in waist circumferance after 26 weeks of treatment is presented.

14. 9-point SMPG Profile [Week 26]

    Participants measured their PG levels using blood glucose meters at 9 time points (before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before dinner, 90 minutes after the start of dinner, at bedtime, at 4 am, before breakfast the following day). 9-point SMPG values at 26 weeks of treatment are presented.

15. Change in Mean of 9-point SMPG Profile [Week 0, week 26]

    Participants measured their PG levels using blood glucose meters at 9 time points (before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before dinner, 90 minutes after the start of dinner, at bedtime, at 4 am, 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.

16. Change in Mean Post-prandial Plasma Glucose (PG) Increments [Week 0, week 26]

    Participants measured their PG levels using blood glucose meters at 9 time points (before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before dinner, 90 minutes after the start of dinner, at bedtime, at 4 am, before breakfast the following day). Post-prandial SMPG increments from before meal to 90 minutes after for breakfast, lunch and dinner were calculated. The mean increment over all meals was derived as the mean of all available meal increments. Change from baseline (week 0) in post-prandial SMPG increments for all meals after 26 weeks of treatment is presented.

17. 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.

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

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

19. 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.

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

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

21. 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.

22. 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

23. 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.

24. 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

25. 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.

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

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

27. Number of Treatment-emergent Adverse Events (TEAE) [Weeks 0-26]

    A TEAE was defined as an event that had onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment. The observed rates of adverse events (AEs) per patient years of exposure (PYE) (number of AEs divided by PYE multiplied by 100) after 26 weeks are presented.

28. Number of Treatment Emergent Nocturnal Severe or BG Confirmed Hypoglycaemic Episodes. [Weeks 0-26]

    Severe or BG confirmed hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification (requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or BG confirmed by a PG 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. Hypoglycaemic episodes were defined as nocturnal if the time of the onset was between 00:01 and 05.59 both inclusive. The number of episodes are represented as rates. The observed rates of episodes per PYE (number of episodes divided by PYE multiplied by 100) after 26 weeks of treatment are presented.

29. Number of Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes. [Weeks 0-26]

    Severe or BG confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification (requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or BG confirmed by a PG 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. The number of episodes are represented as rates. The observed rates of episodes per PYE (number of episodes divided by PYE multiplied by 100) after 26 weeks of treatment are presented.

30. Number of Treatment Emergent Nocturnal Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes [Weeks 0-26]

    Severe or BG confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification (requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or BG confirmed by a PG 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. Hypoglycaemic episodes were defined as nocturnal if the time of the onset was between 00:01 and 05.59 both inclusive. The number of episodes are represented as rates. The observed rates of episodes per PYE (number of episodes divided by PYE multiplied by 100) after 26 weeks of treatment are presented.

31. Number of Treatment Emergent Hypoglycaemic Episodes According to ADA Definition [Weeks 0-26]

    A hypoglycaemic episode was 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 days after the last day on trial product. The number of episodes are represented as rates. The observed rates of episodes (according to the ADA definition) per PYE (number of episodes divided by PYE multiplied by 100) after 26 weeks of treatment are 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 screening (week -2) and week 26 per each category is presented.

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

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

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

    Electrocardiogram was assessed by the investigator as normal, abnormal NCS and abnormal CS. Number of participants at screening (week -2) and at week 26 is presented.

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

    Change in pulse from baseline (week 0) after 26 weeks of treatment 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) after 26 weeks of treatment is presented

37. Change in Biochemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase, Amalyse, Lipase, Creatiine Kinase Serum [Week 0, week 26]

    Change in alkaline phosphatase, ALT, AST, creatine kinase, amylase, lipase, creatine kinase serum from baseline (week 0) after 26 weeks of treatment is presented.

38. Change in Biochemistry Parameters (Albumin Serum, Total Protein) [Week 0, week 26]

    Change in total protein, albumin serum from baseline (week 0) after 26 weeks of treatment is presented.

39. Change in Biochemistry Parameters: Calcium Serum (Total), Calcium Corrected Serum, Potassium Serum, Sodium Serum, Urea Serum [Week 0, week 26]

    Change in calcium serum (total), calcium corrected serum, potassium serum, sodium serum, urea serum from baseline (week 0) after 26 weeks of treatment is presented.

40. Change in Biochemistry Parameters: Total Bilirubin Serum, Creatinine Serum [Week 0, week 26]

    Change in total bilirubin serum, creatinine serum from baseline (week 0) after 26 weeks of treatment is presented.

41. Change in Haematological Parameter: Erythrocytes Blood [Week 0, week 26]

    Change in erythrocyte blood from baseline (week 0) after 26 weeks of treatment is presented.

42. Change in Haematological Parameter: Haematocrits [Week 0, week 26]

    Change in haematocrits from baseline (week 0) after 26 weeks of treatment is presented.

43. Change in Haemotological Parameter- Eosinophils [Week 0, week 26]

    Change in eosinophils from baseline after 26 weeks of treatment is presented.

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

    Change in neutrophils from baseline (week 0) after 26 weeks of treatment is presented.

45. Change in Haematological Parameter: Basophils [Week 0, week 26]

    Change in basophils from baseline (week 0) after 26 weeks of treatment is presented.

46. Change in Haemotological Parameter- Monocytes [Week 0, week 26]

    Change in monocytes from baseline (week 0) after 26 weeks of treatment is presented

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

    Change in lymphocytes from baseline (week 0) after 26 weeks of treatment is presented

48. Change in Haematology: Haemoglobin Blood [Week 0, week 26]

    Change in haemoglobin from baseline (week 0) after 26 weeks of treatment is presented.

49. Change in Haematologcal Parameter: Leukocytes [Week 0, week 26]

    Change in leukocytes from baseline (week 0) after 26 weeks of treatment

50. Change in Haematological Parameter: Thrombocytes [Week 0, week 26]

    Change in thrombocytes from baseline (week 0) after 26 weeks of treatment

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

    Calcitonin levels were measured and were categorised as low, normal or high in relation to reference range (8.31- 14.3 picogram/milliliter [pg/mL]). Number of participants in each category at baseline (week 0) and week 26 are presented.

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

    The urinalysis assessment was the measurements of protein, glucose, erythrocytes and ketones in urine at baseline (week 0) and week 26 and categorised as negative, trace and positive. Number of participants in each category at week 0 and week 26 is presented.

53. Occurence of Anti-insulin Degludec Specific Antibodies [Week 27]

    This outcome measure is only applicable for the insulin degludec/liraglutide arm and insulin degludec arm. Serum samples were analysed for the presence of anti-insulin degludec specific antibodies. Results at week 27 are presented as percentage of bound radioactive-labelled insulin (B) /total radioactive-labelled insulin added to the samples (T).

54. Occurence of Antibodies Cross-reacting to Human Insulin [Week 27]

    This outcome measure is only applicable for the insulin degludec/liraglutide arm and insulin degludec arm. Serum samples were analysed for the presence of cross-reacting antibodies to human insulin. Results at week 27 are presented as percentage of bound radioactive-labelled insulin (B) /total radioactive-labelled insulin added to the samples (T).

55. Occurence of Total Insulin Antibodies [Week 27]

    This outcome measure is only applicable for the Insulin degludec/liraglutide arm and Insulin degludec arm. Serum samples were analysed for the presence of antobodies to human insulin. Results at week 27 are presented as percentage of bound radioactive-labelled insulin (B) /total radioactive-labelled insulin added to the samples (T).

56. Occurence of Anti-liraglutide Antibodies [Week 27]

    This outcome measure is applicable for the Insulin degludec/liraglutide arm and the liraglutide arm. Serum samples were analysed for the presence of anti-liraglutide antibodies. Number of participants who were assessed for anti-liraglutide antibodies at week 27 are presented.

57. Occurence of Antibodies Cross-reacting to Native Glucagon-like Peptide (GLP-1) [Week 27]

    This outcome measure is applicable to the Insulin degludec/liraglutide arm and the liraglutide arm. Serum samples were analysed for the presence of cross-reacting antibodies to native GLP-1. Number of participants who measured with anti-liraglutide antibodies cross reacting native GLP-1 at week 27 are presented.

58. Occurence of Neutralising Liraglutide Antibodies [Week 27]

    This outcome measure is only applicable for the Insulin degludec/liraglutide arm and liraglutide arm. Neutralising antibodies were assessed when the corresponding anti-Liraglutide antibody were positive at week 27. Number of participants who measured with neutralising liraglutide antibodies at week 27 are presented.

59. Occurence of Neutralising Antibodies Cross-reacting to Native GLP-1 [Week 27]

    This outcome measure is only applicable for the Insulin degludec/liraglutide arm and liraglutide arm. Cross reacting antibodies were assessed when anti-liraglutide antibody was positive. Number of participants who measured with neutralising liraglutide antibodies cross-reacting to native GLP-1 at week 27 are presented.

60. Serum Concentrations of Insulin Degludec [Week 0, week 26]

    This outcome measure is applicable for Insulin degludec and Insulin degludec/liraglutide arms. Serum samples from the Insulin degludec/liraglutide and Insulin degludec arms were assayed using population PK analysis. The maximum serum concentrations (Cmax) are summarised for the two arms.

61. Plasma Concentration of Liraglutide [Week 0, week 26]

    This outcome measure is for Insulin degludec/liraglutide and liraglutide arms. Serum samples from the Insulin degludec/liraglutide and liraglutide arms were assayed using population PK analysis. The Cmax are summarised for the two arms.

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 activities to determine suitability for the trial

• Type 2 diabetes mellitus (clinically diagnosed)

• Male or female, age at least 18 years at the time of signing informed consent

• HbA1c 7.0-10.0 % (both inclusive) by central laboratory analysis, with the aim of a median of8.3%. When approximately 50% of the randomised subjects have an HbA1c above 8.3%, the remaining subjects randomised must have an HbA1c below or equal to 8.3%; or when approximately 50% of the randomised subjects have an HbA1c below or equal to 8.3%, the remaining subjects randomised must have an HbA1c above 8.3%

• Current treatment for at least 90 calendar days prior to screening with metformin plus/minus one other OAD: α-glucosidase inhibitors, sulphonylureas, glinides or thiazolidinediones. For above or equal to 60 calendar days prior to screening subjects should be on a stable dose of:

• 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 glinides (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 α-glucosidase inhibitors (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 thiazolidinediones (above or equal to half of the max approved dose according to local label)

Exclusion Criteria:

• Treatment with insulin (except for short-term treatment at the discretion of the investigator)

• Treatment with glucagon-like-peptide-1 receptor agonists or dipeptidyl-peptidase-4 inhibitors within 90 days prior to screening

• 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 mmHg or diastolic blood pressure above or equal to 100 mmHg

• 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	230061
2	Novo Nordisk Investigational Site	Beijing	Beijing	China	100071
3	Novo Nordisk Investigational Site	ChongQing	Chongqing	China	404000
4	Novo Nordisk Investigational Site	Fuzhou	Fujian	China	350001
5	Novo Nordisk Investigational Site	Fuzhou	Fujian	China	350025
6	Novo Nordisk Investigational Site	Guangzhou	Guangdong	China	510080
7	Novo Nordisk Investigational Site	Guangzhou	Guangdong	China	510120
8	Novo Nordisk Investigational Site	Guangzhou	Guangdong	China	510515
9	Novo Nordisk Investigational Site	Cangzhou	Hebei	China	061000
10	Novo Nordisk Investigational Site	Shijiazhuang	Hebei	China	050000
11	Novo Nordisk Investigational Site	Shijiazhuang	Hebei	China	050051
12	Novo Nordisk Investigational Site	Changzhou	Jiangsu	China	213003
13	Novo Nordisk Investigational Site	Huai'an	Jiangsu	China	223002
14	Novo Nordisk Investigational Site	Huai'an	Jiangsu	China	223300
15	Novo Nordisk Investigational Site	Nanjing	Jiangsu	China	210011
16	Novo Nordisk Investigational Site	Nanjing	Jiangsu	China	210012
17	Novo Nordisk Investigational Site	Nanjing	Jiangsu	China	210029
18	Novo Nordisk Investigational Site	Zhenjiang	Jiangsu	China	212001
19	Novo Nordisk Investigational Site	Nanchang	Jiangxi	China	330006
20	Novo Nordisk Investigational Site	Nanchang	Jiangxi	China
21	Novo Nordisk Investigational Site	Changchun	Jilin	China	130021
22	Novo Nordisk Investigational Site	Dalian	Liaoning	China	116011
23	Novo Nordisk Investigational Site	Yinchuan	Ningxia	China	750004
24	Novo Nordisk Investigational Site	Xi'an	Shaanxi	China	710061
25	Novo Nordisk Investigational Site	Jinan	Shandong	China	250013
26	Novo Nordisk Investigational Site	Pudong New District	Shanghai	China	201200
27	Novo Nordisk Investigational Site	Shanghai	Shanghai	China	200025
28	Novo Nordisk Investigational Site	Shanghai	Shanghai	China	200040
29	Novo Nordisk Investigational Site	Shanghai	Shanghai	China	200072
30	Novo Nordisk Investigational Site	Shanghai	Shanghai	China	200080
31	Novo Nordisk Investigational Site	Shanghai	Shanghai	China	200123
32	Novo Nordisk Investigational Site	Shanghai	Shanghai	China	200240
33	Novo Nordisk Investigational Site	Shanghai	Shanghai	China	200336
34	Novo Nordisk Investigational Site	Tianjin	Tianjin	China	300052
35	Novo Nordisk Investigational Site	Kunming	Yunnan	China	650101
36	Novo Nordisk Investigational Site	Beijing		China	101200
37	Novo Nordisk Investigational Site	Fuzhou		China	350005

Sponsors and Collaborators

• Novo Nordisk A/S

Investigators

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

Study Documents (Full-Text)

• Study Protocol - Dec 16, 2019
• Statistical Analysis Plan - Dec 16, 2019

More Information

Publications

None provided.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT03172494
• Other Study ID Numbers: NN9068-4148; U1111-1154-6671; CTR20170004
• First Posted: Jun 1, 2017
• Last Update Posted: Jul 7, 2020
• Last Verified: Jun 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 38 sites in China mainland.
Pre-assignment Detail	Participants were randomised in a 2:1:1 manner to receive insulin degludec/liraglutide, insulin degludec or liraglutide in combination with metformin.

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 milligrams (mg) liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 millimoles/litre (mmol/L). The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg per day (mg/day) was continued for the remaining period of treatment."
Period Title: Overall Study
STARTED	361	179	180
Full Analysis Set (FAS)	361	179	180
Safety Analysis Set (SAS)	358	175	180
Exposed	358	175	180
COMPLETED	341	167	151
NOT COMPLETED	20	12	29

Baseline Characteristics

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide	Total
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."	Total of all reporting groups
Overall Participants	361	179	180	720
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.5 (10.3)	55.7 (10.2)	54.1 (10.2)	54.7 (10.3)
Sex/Gender, Customized (Count of Participants)
Female	142 39.3%	79 44.1%	72 40%	293 40.7%
Male	219 60.7%	100 55.9%	108 60%	427 59.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	361 100%	179 100%	180 100%	720 100%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	361 100%	179 100%	180 100%	720 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Glycosylated haemoglobin (HbA1c) (Percentage points of HbA1c) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percentage points of HbA1c]	8.20 (0.83)	8.31 (0.84)	8.21 (0.77)	8.23 (0.82)

Outcome Measures

1. Primary Outcome

Title	Change in HbA1c
Description	Change in HbA1c from baseline (week 0) after 26 weeks of treatment 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	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	341	167	151
Mean (Standard Deviation) [Percentage points of HbA1c]	-1.71 (0.88)	-1.20 (0.99)	-1.16 (0.89)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Degludec/Liraglutide, Insulin Degludec
	Comments	The change from baseline in HbA1c after 26 weeks of treatment was analysed using an analysis of covariance (ANCOVA) model with treatment and previous oral anti-diabetic (OAD) treatment as fixed factors and baseline HbA1c as covariate. Missing values were imputed by last observation carried forward (LOCF).
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority of insulin degludec/liraglutide versus insulin degludec was considered as confirmed if the 95% confidence interval (CI) for the mean treatment difference lied entirely below 0.4%. Non-inferiority was investigated on the FAS.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean treatment difference
	Estimated Value	-0.59
	Confidence Interval	(2-Sided) 95%; -0.73 to -0.46
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Insulin Degludec/Liraglutide, Liraglutide
	Comments	The change from baseline in HbA1c after 26 weeks of treatment was analysed using an ANCOVA model with treatment and previous OAD treatment as fixed factors and baseline HbA1c as covariate. Missing values were imputed by LOCF.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean treatment difference
	Estimated Value	-0.63
	Confidence Interval	(2-Sided) 95%; -0.76 to -0.49
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change in Body Weight
Description	Change in body weight from baseline (week 0) after 26 weeks of treatment 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	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	341	167	151
Mean (Standard Deviation) [Kilogram (Kg)]	0.2 (2.7)	1.3 (2.7)	-2.5 (2.7)

3. Secondary Outcome

Title	Number of 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 American Diabetes Association (ADA) classification (requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or blood glucose (BG) confirmed by a plasma glucose (PG) 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. The number of episodes are represented as rates. The observed rates of treatment-emergent severe or BG confirmed hypoglycaemic episodes per patient years of exposure (PYE) (number of episodes divided by PYE multiplied by 100) during 26 weeks of treatment are presented.
Time Frame	Weeks 0-26

Outcome Measure Data

Analysis Population Description

Safety analysis set (SAS) included all participants who received at least one dose of insulin degludec/liraglutide, insulin degludec or liraglutide. Overall number of participants analysed = number of participants with available data.

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	29	14	3
Number [(Number of episodes/PYE)*100]	23.94	17.01	3.60

4. Secondary Outcome

Title	Insulin Dose
Description	The actual daily total insulin dose after 26 weeks of treatment is presented. This outcome measure is only applicable for Insulin degludec/liraglutide and Insulin degludec treatment arms.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

SAS included all participants receiving at least one dose of the insulin degludec/liraglutide or insulin degludec. 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 subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.
Measure Participants	340	167
Mean (Standard Deviation) [Units of insulin (U)]	24.8 (11.9)	30.1 (14.4)

5. Secondary Outcome

Title	Participants Who Achieved HbA1c < 7.0%, American Diabetes Association (ADA) Target (Yes/no)
Description	Number of participants who achieved ADA HbA1c target (HbA1c < 7.0%) (yes/no) after 26 weeks of treatment are presented.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	341	167	151
Yes	272 75.3%	83 46.4%	80 44.4%
No	69 19.1%	84 46.9%	71 39.4%

6. Secondary Outcome

Title	Participants Who Achieved HbA1c ≤ 6.5%, International Diabetes Federation (IDF) Target (Yes/no)
Description	Number of participants who achieved IDF HbA1c target (HbA1c ≤ 6.5%) (yes/no) after 26 weeks of treatment are presented.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	341	167	151
Yes	201 55.7%	48 26.8%	41 22.8%
No	140 38.8%	119 66.5%	110 61.1%

7. Secondary Outcome

Title	Participants Who Achieved HbA1c <7.0% and Change in Body Weight From Baseline Below or Equal to Zero
Description	Number of participants who achieved ADA HbA1c target (HbA1c < 7.0%) (yes/no) and change from baseline in body weight below or equal to zero after 26 weeks are presented. Missing values are imputed by LOCF.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

FAS included all randomised participants.

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	361	179	180
Yes	147 40.7%	34 19%	74 41.1%
No	214 59.3%	145 81%	106 58.9%

8. Secondary Outcome

Title	Participants Who Achieved HbA1c ≤ 6.5% and Change From Baseline in Body Weight Below or Equal to Zero
Description	Number of participants who achieved IDF HbA1c target (HbA1c ≤ 6.5%) (yes/no) and change from baseline in body weight below or equal to zero after 26 weeks are presented. Missing values are imputed by LOCF.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

FAS included all randomised participants.

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	361	179	180
Yes	111 30.7%	21 11.7%	37 20.6%
No	250 69.3%	158 88.3%	143 79.4%

9. Secondary Outcome

Title	Participants Who Achieved HbA1c < 7.0% Without 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 ADA classification (required assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or BG confirmed by a PG 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. Number of participants who achieved ADA HbA1c target (HbA1c <7.0%) (yes/no) after 26 weeks of treatment and without severe or BG confirmed hypoglycaemic episodes during the last 12 weeks of treatment are presented. Missing values are imputed by LOCF.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

FAS included all randomised participants.

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	361	179	180
Yes	265 73.4%	80 44.7%	84 46.7%
No	96 26.6%	99 55.3%	96 53.3%

10. Secondary Outcome

Title	Participants Who Achieved HbA1c ≤ 6.5% Without 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 PG 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. Number of participants who achieved IDF HbA1c target (HbA1c ≤ 6.5%) (yes/no) after 26 weeks of treatment and without severe or BG confirmed hypoglycaemic episodes during the last 12 weeks of treatment are presented. Missing values are imputed by LOCF.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

FAS included all randomised participants.

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	361	179	180
Yes	195 54%	46 25.7%	43 23.9%
No	166 46%	133 74.3%	137 76.1%

11. Secondary Outcome

Title	Participants Who Achieved HbA1c < 7.0% Without Severe or BG Confirmed Episodes, and Change From Baseline in Body Weight Below or Equal to Zero.
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 PG 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. Number of participants who achieved ADA HbA1c target (HbA1c < 7.0%) (yes/no) after 26 weeks of treatment without severe or BG confirmed hypoglycaemic episodes during the last 12 weeks of treatment and with change from baseline in body weight below or equal to zero are presented. Missing values are imputed by LOCF.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

FAS included all randomised participants.

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	361	179	180
Yes	136 37.7%	33 18.4%	72 40%
No	225 62.3%	146 81.6%	108 60%

12. Secondary Outcome

Title	Participants Who Achieved HbA1c ≤ 6.5% Without Severe or BG Confirmed Episodes and Change From Baseline in Body Weight Below or Equal to Zero.
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 PG 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. Number of participants who achieved IDF HbA1c target (HbA1c ≤ 6.5%) (yes/no) after 26 weeks of treatment without severe or BG confirmed hypoglycaemic episodes during the last 12 weeks of treatment and with change from baseline in body weight below or equal to zero are presented. Missing values are imputed by LOCF.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

FAS included all randomised participants.

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	361	179	180
Yes	103 28.5%	21 11.7%	36 20%
No	258 71.5%	158 88.3%	144 80%

13. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	341	167	150
Mean (Standard Deviation) [mmol/L]	-3.64 (2.27)	-3.45 (2.34)	-1.86 (2.11)

14. Secondary Outcome

Title	Change in Waist Circumferance
Description	Change from baseline (week 0) in waist circumferance after 26 weeks of treatment 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	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	341	166	151
Mean (Standard Deviation) [Centimeters (cm)]	-0.3 (3.4)	1.2 (4.2)	-2.6 (3.8)

15. Secondary Outcome

Title	9-point SMPG Profile
Description	Participants measured their PG levels using blood glucose meters at 9 time points (before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before dinner, 90 minutes after the start of dinner, at bedtime, at 4 am, before breakfast the following day). 9-point SMPG values at 26 weeks of treatment are presented.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	361	179	180
Before breakfast	5.41 (1.07)	5.66 (1.20)	6.89 (1.37)
90 minutes after the start of breakfast	8.97 (2.48)	9.85 (2.73)	10.04 (2.81)
Before lunch	6.31 (1.80)	7.10 (2.35)	7.48 (2.14)
90 minutes after the start of the lunch	8.87 (2.15)	10.18 (2.81)	9.54 (2.43)
Before dinner	6.52 (1.77)	7.39 (2.23)	7.50 (2.11)
90 minutes after start of the dinner	9.33 (2.40)	10.27 (2.68)	9.45 (2.13)
At bedtime	7.99 (2.28)	8.86 (2.38)	8.49 (2.26)
At 4:00 am	5.60 (1.26)	6.12 (1.75)	6.86 (1.60)
Before breakfast the following day	5.35 (0.96)	5.47 (1.07)	6.81 (1.47)

16. Secondary Outcome

Title	Change in Mean of 9-point SMPG Profile
Description	Participants measured their PG levels using blood glucose meters at 9 time points (before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before dinner, 90 minutes after the start of dinner, at bedtime, at 4 am, 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 = number of participants with available data.

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	331	162	146
Mean (Standard Deviation) [mmol/L]	-3.17 (2.16)	-2.47 (2.14)	-2.13 (2.02)

17. Secondary Outcome

Title	Change in Mean Post-prandial Plasma Glucose (PG) Increments
Description	Participants measured their PG levels using blood glucose meters at 9 time points (before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before dinner, 90 minutes after the start of dinner, at bedtime, at 4 am, before breakfast the following day). Post-prandial SMPG increments from before meal to 90 minutes after for breakfast, lunch and dinner were calculated. The mean increment over all meals was derived as the mean of all available meal increments. Change from baseline (week 0) in post-prandial SMPG increments for all meals after 26 weeks of treatment is presented.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	335	164	150
Mean (Standard Deviation) [mmol/L]	-0.20 (2.40)	0.09 (2.40)	-0.54 (2.57)

18. 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 = number of participants with available data.

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	339	167	150
Geometric Mean (Geometric Coefficient of Variation) [Ratio of fasting C-peptide]	0.54 (52.8)	0.38 (68.5)	0.98 (37.6)

19. Secondary Outcome

Title	Change in Fasting Human Insulin - Ratio to Baseline
Description	Change in fasting human 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 = number of participants with available data.

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	328	162	142
Geometric Mean (Geometric Coefficient of Variation) [Ratio of fasting human insulin]	0.53 (71.7)	0.38 (77.6)	1.04 (53.3)

20. 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 particiapants analysed = number of participants with available data.

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	338	165	150
Geometric Mean (Geometric Coefficient of Variation) [Ratio of fasting glucagon]	0.90 (76.6)	0.95 (56.4)	0.98 (75.9)

21. Secondary Outcome

Title	Change in HOMA-B (Beta Cell Function)- Ratio to Baseline
Description	Change in HOMA-B (measured in %) 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 = number of participants with available data.

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	328	162	141
Geometric Mean (Geometric Coefficient of Variation) [Ratio of HOMA-B (beta cell function)]	1.38 (77.3)	0.94 (77.4)	1.53 (63.8)

22. 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 = number of participants with available data

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	341	167	151
Geometric Mean (Geometric Coefficient of Variation) [Ratio of fasting total cholesterol]	0.94 (19.1)	0.99 (16.8)	0.97 (17.7)

23. 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 = number of participants with available data.

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	341	167	151
Geometric Mean (Geometric Coefficient of Variation) [Ratio of fasting HDL cholesterol]	1.01 (14.7)	1.02 (15.7)	1.03 (14.8)

24. 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 = number of participants with available data.

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	340	167	151
Geometric Mean (Geometric Coefficient of Variation) [Ratio of fasting LDL cholesterol]	0.92 (34.2)	1.01 (36.2)	0.96 (34.4)

25. 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 = number of participants with available data.

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	341	167	151
Geometric Mean (Geometric Coefficient of Variation) [Ratio of fasting VLDL cholesterol]	0.90 (49.9)	0.84 (47.2)	0.92 (38.6)

26. 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 = number of participants with available data.

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	341	167	151
Geometric Mean (Geometric Coefficient of Variation) [Ratio of fasting triglycerides]	0.88 (54.4)	0.82 (50.5)	0.90 (45.2)

27. Secondary Outcome

Title	Change in Fasting Free Fatty Acid - Ratio to Baseline
Description	Change in fasting free fatty acid (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 = number of participants with available data.

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	340	167	150
Geometric Mean (Geometric Coefficient of Variation) [Ratio of fasting free fatty acid]	0.55 (69.9)	0.48 (76.5)	0.80 (69.3)

28. Secondary Outcome

Title	Number of Treatment-emergent Adverse Events (TEAE)
Description	A TEAE was defined as an event that had onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment. The observed rates of adverse events (AEs) per patient years of exposure (PYE) (number of AEs divided by PYE multiplied by 100) after 26 weeks are presented.
Time Frame	Weeks 0-26

Outcome Measure Data

Analysis Population Description

SAS included all participants who received at least one dose of Insulin degludec/liraglutide, insulin degludec or liraglutide. Number of participants analysed = number of participants with available data.

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	267	117	143
Number [(Number of AEs/PYE)*100]	410.82	306.19	541.00

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 (requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or BG confirmed by a PG 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. Hypoglycaemic episodes were defined as nocturnal if the time of the onset was between 00:01 and 05.59 both inclusive. The number of episodes are represented as rates. The observed rates of episodes per PYE (number of episodes divided by PYE multiplied by 100) after 26 weeks of treatment are presented.
Time Frame	Weeks 0-26

Outcome Measure Data

Analysis Population Description

SAS included all participants who received at least one dose of insulin degludec/liraglutide, insulin degludec or liraglutide. Overall number of participants analysed = number of participants with available data.

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	6	4	0
Number [(Number of episodes/PYE)*100]	4.45	4.54

30. Secondary Outcome

Title	Number of Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes.
Description	Severe or BG confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification (requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or BG confirmed by a PG 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. The number of episodes are represented as rates. The observed rates of episodes per PYE (number of episodes divided by PYE multiplied by 100) after 26 weeks of treatment are presented.
Time Frame	Weeks 0-26

Outcome Measure Data

Analysis Population Description

SAS included all participants who received at least one dose of Insulin degludec/liraglutide, insulin degludec or liraglutide. Overall number of participants analysed = number of participants with available data.

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	20	8	1
Number [(Number of episodes/PYE)*100]	15.03	9.07	1.20

31. Secondary Outcome

Title	Number of Treatment Emergent Nocturnal Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes
Description	Severe or BG confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification (requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or BG confirmed by a PG 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. Hypoglycaemic episodes were defined as nocturnal if the time of the onset was between 00:01 and 05.59 both inclusive. The number of episodes are represented as rates. The observed rates of episodes per PYE (number of episodes divided by PYE multiplied by 100) after 26 weeks of treatment are presented.
Time Frame	Weeks 0-26

Outcome Measure Data

Analysis Population Description

SAS included all participants who received at least one dose of Insulin degludec/liraglutide, insulin degludec or liraglutide. Overall number of participants analysed = number of participants with available data.

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	5	3	0
Number [(Number of episodes/PYE)*100]	2.78	3.40

32. Secondary Outcome

Title	Number of Treatment Emergent Hypoglycaemic Episodes According to ADA Definition
Description	A hypoglycaemic episode was 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 days after the last day on trial product. The number of episodes are represented as rates. The observed rates of episodes (according to the ADA definition) per PYE (number of episodes divided by PYE multiplied by 100) after 26 weeks of treatment are presented.
Time Frame	Weeks 0-26

Outcome Measure Data

Analysis Population Description

SAS included all participants who received at least one dose of insulin degludec/liraglutide, insulin degludec or liraglutide. Overall number of participants analysed = number of participants with available data.

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	236	123	19
Number [(Number of episodes/PYE)*100]	668.55	746.20	37.19

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 screening (week -2) and week 26 per each category 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 Insulin degludec/liraglutide, insulin degludec or liraglutide. Overall number of participants analyzed=participants with available data

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	358	175	180
Normal	353 97.8%	173 96.6%	180 100%
Abnormal, NCS	2 0.6%	2 1.1%	0 0%
Abnormal CS	3 0.8%	0 0%	0 0%
Normal	336 93.1%	166 92.7%	151 83.9%
Abnormal, NCS	3 0.8%	1 0.6%	0 0%
Abnormal CS	2 0.6%	0 0%	0 0%
Normal	355 98.3%	172 96.1%	179 99.4%
Abnormal, NCS	1 0.3%	0 0%	0 0%
Abnormal CS	2 0.6%	3 1.7%	1 0.6%
Normal	338 93.6%	164 91.6%	150 83.3%
Abnormal, NCS	1 0.3%	0 0%	0 0%
Abnormal CS	2 0.6%	3 1.7%	1 0.6%
Normal	355 98.3%	174 97.2%	179 99.4%
Abnormal, NCS	3 0.8%	1 0.6%	1 0.6%
Abnormal CS	0 0%	0 0%	0 0%
Normal	339 93.9%	166 92.7%	150 83.3%
Abnormal, NCS	2 0.6%	1 0.6%	1 0.6%
Abnormal CS	0 0%	0 0%	0 0%
Normal	351 97.2%	169 94.4%	177 98.3%
Abnormal, NCS	3 0.8%	2 1.1%	1 0.6%
Abnormal CS	4 1.1%	4 2.2%	2 1.1%
Normal	336 93.1%	161 89.9%	150 83.3%
Abnormal, NCS	2 0.6%	2 1.1%	0 0%
Abnormal CS	3 0.8%	4 2.2%	1 0.6%
Normal	348 96.4%	170 95%	175 97.2%
Abnormal, NCS	6 1.7%	4 2.2%	3 1.7%
Abnormal CS	4 1.1%	1 0.6%	2 1.1%
Normal	332 92%	164 91.6%	150 83.3%
Abnormal, NCS	6 1.7%	3 1.7%	1 0.6%
Abnormal CS	3 0.8%	0 0%	0 0%
Normal	357 98.9%	174 97.2%	180 100%
Abnormal, NCS	0 0%	0 0%	0 0%
Abnormal CS	1 0.3%	1 0.6%	0 0%
Normal	340 94.2%	166 92.7%	151 83.9%
Abnormal, NCS	0 0%	0 0%	0 0%
Abnormal CS	1 0.3%	1 0.6%	0 0%
Normal	353 97.8%	172 96.1%	177 98.3%
Abnormal, NCS	2 0.6%	2 1.1%	0 0%
Abnormal CS	3 0.8%	1 0.6%	3 1.7%
Normal	332 92%	165 92.2%	149 82.8%
Abnormal, NCS	2 0.6%	1 0.6%	0 0%
Abnormal CS	7 1.9%	1 0.6%	2 1.1%
Normal	358 99.2%	175 97.8%	180 100%
Abnormal, NCS	0 0%	0 0%	0 0%
Abnormal CS	0 0%	0 0%	0 0%
Normal	341 94.5%	167 93.3%	151 83.9%
Abnormal, NCS	0 0%	0 0%	0 0%
Abnormal CS	0 0%	0 0%	0 0%
Normal	312 86.4%	152 84.9%	156 86.7%
Abnormal, NCS	37 10.2%	20 11.2%	20 11.1%
Abnormal CS	9 2.5%	3 1.7%	4 2.2%
Normal	297 82.3%	146 81.6%	134 74.4%
Abnormal, NCS	36 10%	19 10.6%	15 8.3%
Abnormal CS	8 2.2%	2 1.1%	2 1.1%
Normal	348 96.4%	171 95.5%	179 99.4%
Abnormal, NCS	5 1.4%	1 0.6%	1 0.6%
Abnormal CS	5 1.4%	3 1.7%	0 0%
Normal	334 92.5%	163 91.1%	151 83.9%
Abnormal, NCS	3 0.8%	2 1.1%	0 0%
Abnormal CS	4 1.1%	2 1.1%	0 0%

34. Secondary Outcome

Title	Eye Examination
Description	Dilated fundoscopy or fundus photography was performed by the investigator at screening (week -2) and week 26. The results of the examination were interpreted for each eye (left and right) and are categorised as normal, abnormal NCS or abnormal CS. Number of participants in each category at screening (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 insulin degludec/liraglutide, insulin degludec or liraglutide. Overall number of participants analyzed = participants with available data.

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	358	175	180
Normal	222 61.5%	109 60.9%	110 61.1%
Abnormal, NCS	45 12.5%	14 7.8%	20 11.1%
Abnormal, CS	91 25.2%	52 29.1%	50 27.8%
Normal	217 60.1%	99 55.3%	100 55.6%
Abnormal, NCS	39 10.8%	20 11.2%	13 7.2%
Abnormal, CS	85 23.5%	48 26.8%	38 21.1%
Normal	230 63.7%	112 62.6%	111 61.7%
Abnormal, NCS	42 11.6%	16 8.9%	22 12.2%
Abnormal, CS	86 23.8%	47 26.3%	47 26.1%
Normal	217 60.1%	103 57.5%	96 53.3%
Abnormal, NCS	40 11.1%	23 12.8%	15 8.3%
Abnormal, CS	84 23.3%	41 22.9%	40 22.2%

35. Secondary Outcome

Title	Change in Electrocardiogram (ECG)
Description	Electrocardiogram was assessed by the investigator as normal, abnormal NCS and abnormal CS. Number of participants at screening (week -2) and at 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 insulin degludec/liraglutide, insulin degludec or liraglutide. Number of participants analyzed = participants with available data.

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	358	175	180
Normal	223 61.8%	109 60.9%	108 60%
Abnormal, NCS	94 26%	46 25.7%	52 28.9%
Abnormal CS	41 11.4%	20 11.2%	20 11.1%
Normal	227 62.9%	108 60.3%	87 48.3%
Abnormal, NCS	76 21.1%	47 26.3%	40 22.2%
Abnormal CS	38 10.5%	12 6.7%	24 13.3%

36. Secondary Outcome

Title	Change in Pulse
Description	Change in pulse from baseline (week 0) after 26 weeks of treatment 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 insulin degludec/liraglutide, insulin degludec or liraglutide. Overall number of participants analysed = number of participants with available data.

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	341	167	151
Mean (Standard Deviation) [Beats per minuts (beats/min)]	4.6 (8.6)	-0.1 (8.6)	4.9 (9.7)

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) after 26 weeks of treatment 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 Insulin degludec/liraglutide, insulin degludec or liraglutide. Overall number of participants analysed = number of participants with available data.

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	341	167	151
Systolic blood pressure	-3.5 (12.7)	-1.2 (11.7)	-3.3 (13.8)
Distolic blood pressure	-0.4 (8.3)	-0.7 (8.1)	0.0 (8.4)

38. Secondary Outcome

Title	Change in Biochemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase, Amalyse, Lipase, Creatiine Kinase Serum
Description	Change in alkaline phosphatase, ALT, AST, creatine kinase, amylase, lipase, creatine kinase serum from baseline (week 0) after 26 weeks of treatment 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 Insulin degludec/liraglutide, insulin degludec or liraglutide. Overall number of participants analysed = number of participants with available data.

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	341	167	151
Alkaline phosphatase	-2.0 (14.85)	-2.29 (11.49)	-0.48 (14.11)
ALT	-4.63 (13.06)	-6.17 (13.54)	-2.81 (16.97)
AST	-1.31 (7.94)	-2.65 (8.40)	-0.99 (9.64)
Creatine kinase	10.67 (100.87)	15.37 (52.99)	0.52 (56.20)
Amylase	9.84 (36.73)	5.09 (14.68)	5.68 (13.70)
Lipase	16.13 (101.19)	-1.87 (15.64)	14.11 (19.76)

39. Secondary Outcome

Title	Change in Biochemistry Parameters (Albumin Serum, Total Protein)
Description	Change in total protein, albumin serum from baseline (week 0) after 26 weeks of treatment 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 Insulin degludec/liraglutide, insulin degludec or liraglutide. Overall number of participants analysed = number of participants with available data.

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	341	167	151
Albumin serum	-0.05 (0.28)	-0.09 (0.26)	0.04 (0.26)
Total protein	-0.08 (0.42)	-0.08 (0.39)	-0.01 (0.39)

40. Secondary Outcome

Title	Change in Biochemistry Parameters: Calcium Serum (Total), Calcium Corrected Serum, Potassium Serum, Sodium Serum, Urea Serum
Description	Change in calcium serum (total), calcium corrected serum, potassium serum, sodium serum, urea serum from baseline (week 0) after 26 weeks of treatment 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 Insulin degludec/liraglutide, insulin degludec or liraglutide. Overall number of participants analysed = number of participants with available data.

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	341	167	151
Calcium serum (total)	-0.01 (0.10)	-0.02 (0.10)	-0.00 (0.09)
Calcium corrected serum	-0.00 (0.08)	-0.00 (0.08)	-0.01 (0.07)
Sodium serum	1.21 (2.09)	0.98 (2.37)	0.32 (2.12)
Urea serum	0.05 (0.57)	0.03 (0.53)	0.16 (0.67)
Potassium serum	-0.04 (0.34)	-0.09 (0.39)	-0.04 (0.34)

41. Secondary Outcome

Title	Change in Biochemistry Parameters: Total Bilirubin Serum, Creatinine Serum
Description	Change in total bilirubin serum, creatinine serum from baseline (week 0) after 26 weeks of treatment 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 Insulin degludec/liraglutide, insulin degludec or liraglutide. Overall number of participants analysed = number of participants with available data.

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	341	167	151
Total bilirubin	-0.78 (3.35)	-0.55 (4.52)	-1.16 (3.92)
creatinine serum	1.02 (8.41)	1.36 (7.92)	-0.60 (7.89)

42. Secondary Outcome

Title	Change in Haematological Parameter: Erythrocytes Blood
Description	Change in erythrocyte blood from baseline (week 0) after 26 weeks of treatment 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 insulin degludec/liraglutide, insulin degludec or liraglutide. Overall number of participants analysed = number of participants with available data.

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	341	167	150
Mean (Standard Deviation) [10^12 cells per liter (10^12/L)]	-0.05 (0.27)	-0.00 (0.27)	-0.05 (0.25)

43. Secondary Outcome

Title	Change in Haematological Parameter: Haematocrits
Description	Change in haematocrits from baseline (week 0) after 26 weeks of treatment 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 Insulin degludec/liraglutide, insulin degludec or liraglutide. Overall number of participants analysed = number of participants with available data.

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	341	167	150
Mean (Standard Deviation) [Percentage points (%) of red blood cells]	-0.56 (2.65)	-0.49 (2.69)	-0.42 (2.57)

44. Secondary Outcome

Title	Change in Haemotological Parameter- Eosinophils
Description	Change in eosinophils from baseline after 26 weeks of treatment 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 Insulin degludec/liraglutide, insulin degludec or liraglutide. Overall number of participants analysed = number of participants with available data

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	341	167	150
Mean (Standard Deviation) [% of eosinophils]	-0.06 (1.90)	0.19 (1.73)	0.11 (1.94)

45. Secondary Outcome

Title	Change in Haematological Parameter - Neutrophils
Description	Change in neutrophils from baseline (week 0) after 26 weeks of treatment 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 Insulin degludec/liraglutide, insulin degludec or liraglutide. Overall number of participants analysed = number of participants with available data

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	341	167	150
Mean (Standard Deviation) [% of neutrophils]	0.57 (6.46)	0.18 (7.70)	-0.53 (7.05)

46. Secondary Outcome

Title	Change in Haematological Parameter: Basophils
Description	Change in basophils from baseline (week 0) after 26 weeks of treatment 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 Insulin degludec/liraglutide, insulin degludec or liraglutide. Overall number of participants analysed = number of participants with available data.

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	341	167	150
Mean (Standard Deviation) [% of basophils]	-0.02 (0.29)	-0.01 (0.28)	-0.03 (0.26)

47. Secondary Outcome

Title	Change in Haemotological Parameter- Monocytes
Description	Change in monocytes from baseline (week 0) after 26 weeks of treatment 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 Insulin degludec/liraglutide, insulin degludec or liraglutide. Overall number of participants analysed = number of participants with available data.

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	341	167	150
Mean (Standard Deviation) [% of monocytes]	-0.03 (1.92)	0.01 (1.85)	0.05 (2.13)

48. Secondary Outcome

Title	Change in Haematological Parameter - Lymphocytes
Description	Change in lymphocytes from baseline (week 0) after 26 weeks of treatment 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 Insulin degludec/liraglutide, insulin degludec or liraglutide. Overall number of participants analysed = number of participants with available data.

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	341	167	150
Mean (Standard Deviation) [% of lymphocytes]	-0.46 (6.04)	-0.38 (7.12)	0.40 (6.11)

49. Secondary Outcome

Title	Change in Haematology: Haemoglobin Blood
Description	Change in haemoglobin from baseline (week 0) after 26 weeks of treatment 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 Insulin degludec/liraglutide, insulin degludec or liraglutide. Overall number of participants analysed = number of participants with available data.

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	341	167	150
Mean (Standard Deviation) [mmol/L]	-0.10 (0.53)	-0.06 (0.48)	-0.05 (0.47)

50. Secondary Outcome

Title	Change in Haematologcal Parameter: Leukocytes
Description	Change in leukocytes from baseline (week 0) after 26 weeks of treatment
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

SAS included all participants who received at least one dose of insulin degludec/liraglutide, insulin degludec or liraglutide. Overall number of participants analysed = number of participants with available data.

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	341	167	150
Mean (Standard Deviation) [10^9 cells per liter (10^9/L)]	0.25 (1.18)	0.23 (1.41)	-0.01 (1.14)

51. Secondary Outcome

Title	Change in Haematological Parameter: Thrombocytes
Description	Change in thrombocytes from baseline (week 0) after 26 weeks of treatment
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

SAS included all participants who received at least one dose of Insulin degludec/liraglutide, insulin degludec or liraglutide. Overall number of participants analysed = number of participants with available data.

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	340	167	149
Mean (Standard Deviation) [10^9 cells per liter (10^9/L)]	8.19 (28.02)	8.32 (34.48)	4.32 (33.39)

52. Secondary Outcome

Title	Change in Calcitonin
Description	Calcitonin levels were measured and were categorised as low, normal or high in relation to reference range (8.31- 14.3 picogram/milliliter [pg/mL]). Number of participants in each category at baseline (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 Insulin degludec/liraglutide, insulin degludec or liraglutide. Number analysed = number of participants with available data.

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	358	175	180
Low	0 0%	0 0%	0 0%
Normal	351 97.2%	172 96.1%	178 98.9%
High	7 1.9%	3 1.7%	2 1.1%
Low	0 0%	0 0%	0 0%
Normal	334 92.5%	165 92.2%	147 81.7%
High	6 1.7%	2 1.1%	3 1.7%

53. Secondary Outcome

Title	Urinalysis (Protein, Glucose, Erythrocytes and Ketones)
Description	The urinalysis assessment was the measurements of protein, glucose, erythrocytes and ketones in urine at baseline (week 0) and week 26 and categorised as negative, trace and positive. Number of participants in each category at week 0 and 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 insulin degludec/liraglutide, insulin degludec or liraglutide. Number of participants analysed = number of participants with available data.

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	357	175	180
Negative	299 82.8%	153 85.5%	156 86.7%
Trace	36 10%	16 8.9%	16 8.9%
Positive	22 6.1%	6 3.4%	8 4.4%
Negative	297 82.3%	146 81.6%	136 75.6%
Trace	28 7.8%	16 8.9%	11 6.1%
Positive	14 3.9%	5 2.8%	4 2.2%
Negative	253 70.1%	119 66.5%	123 68.3%
Trace	35 9.7%	19 10.6%	18 10%
Positive	69 19.1%	37 20.7%	39 21.7%
Negative	322 89.2%	157 87.7%	131 72.8%
Trace	11 3%	3 1.7%	5 2.8%
Positive	6 1.7%	7 3.9%	15 8.3%
Negative	325 90%	152 84.9%	167 92.8%
Trace	25 6.9%	20 11.2%	11 6.1%
Positive	7 1.9%	3 1.7%	2 1.1%
Negative	334 92.5%	163 91.1%	141 78.3%
Trace	4 1.1%	3 1.7%	10 5.6%
Positive	1 0.3%	1 0.6%	0 0%
Negative	216 59.8%	104 58.1%	116 64.4%
Trace	86 23.8%	40 22.3%	37 20.6%
Positive	55 15.2%	31 17.3%	27 15%
Negative	254 70.4%	120 67%	105 58.3%
Trace	58 16.1%	26 14.5%	28 15.6%
Positive	27 7.5%	21 11.7%	18 10%

54. Secondary Outcome

Title	Occurence of Anti-insulin Degludec Specific Antibodies
Description	This outcome measure is only applicable for the insulin degludec/liraglutide arm and insulin degludec arm. Serum samples were analysed for the presence of anti-insulin degludec specific antibodies. Results at week 27 are presented as percentage of bound radioactive-labelled insulin (B) /total radioactive-labelled insulin added to the samples (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 subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.
Measure Participants	332	166
Mean (Standard Deviation) [%B/T]	0.22 (1.02)	0.12 (0.79)

55. Secondary Outcome

Title	Occurence of Antibodies Cross-reacting to Human Insulin
Description	This outcome measure is only applicable for the insulin degludec/liraglutide arm and insulin degludec arm. Serum samples were analysed for the presence of cross-reacting antibodies to human insulin. Results at week 27 are presented as percentage of bound radioactive-labelled insulin (B) /total radioactive-labelled insulin added to the samples (T).
Time Frame	Week 27

Outcome Measure Data

Analysis Population Description

SAS included all participants who received at least one dose of insulin degludec/liraglutide or insulin degludec. 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 subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.
Measure Participants	332	166
Mean (Standard Deviation) [%B/T]	6.61 (15.00)	2.99 (10.89)

56. Secondary Outcome

Title	Occurence of Total Insulin Antibodies
Description	This outcome measure is only applicable for the Insulin degludec/liraglutide arm and Insulin degludec arm. Serum samples were analysed for the presence of antobodies to human insulin. Results at week 27 are presented as percentage of bound radioactive-labelled insulin (B) /total radioactive-labelled insulin added to the samples (T).
Time Frame	Week 27

Outcome Measure Data

Analysis Population Description

SAS included all participants who received at least one dose of insulin degludec/liraglutide or insulin degludec. 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 subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.
Measure Participants	332	166
Mean (Standard Deviation) [%B/T]	6.83 (15.78)	3.11 (11.42)

57. Secondary Outcome

Title	Occurence of Anti-liraglutide Antibodies
Description	This outcome measure is applicable for the Insulin degludec/liraglutide arm and the liraglutide arm. Serum samples were analysed for the presence of anti-liraglutide antibodies. Number of participants who were assessed for 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 insulin degludec/liraglutide or insulin degludec. Overall number of participants analyzed = participants with available data.

Arm/Group Title	Insulin Degludec/Liraglutide	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	332	160
Yes	45 12.5%	40 22.3%
No	287 79.5%	120 67%

58. Secondary Outcome

Title	Occurence of Antibodies Cross-reacting to Native Glucagon-like Peptide (GLP-1)
Description	This outcome measure is applicable to the Insulin degludec/liraglutide arm and the liraglutide arm. Serum samples were analysed for the presence of cross-reacting antibodies to native GLP-1. 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 insulin degludec/liraglutide or insulin degludec. Overall number of participants analyzed = participants with available data.

Arm/Group Title	Insulin Degludec/Liraglutide	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	332	160
Yes	6 1.7%	3 1.7%

59. Secondary Outcome

Title	Occurence of Neutralising Liraglutide Antibodies
Description	This outcome measure is only applicable for the Insulin degludec/liraglutide arm and liraglutide arm. Neutralising antibodies were assessed when the corresponding anti-Liraglutide antibody were positive at week 27. 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 insulin degludec/liraglutide, insulin degludec or liraglutide. Overall number of participants analyzed = participants with available data.

Arm/Group Title	Insulin Degludec/Liraglutide	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	332	160
Yes	9 2.5%	8 4.5%

60. Secondary Outcome

Title	Occurence of Neutralising Antibodies Cross-reacting to Native GLP-1
Description	This outcome measure is only applicable for the Insulin degludec/liraglutide arm and liraglutide arm. Cross reacting antibodies were assessed when anti-liraglutide antibody was positive. Number of participants who measured with neutralising liraglutide antibodies cross-reacting to 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 insulin degludec/liraglutide, insulin degludec or liraglutide. Overall number of participants analyzed = participants with available data.

Arm/Group Title	Insulin Degludec/Liraglutide	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	332	160
Yes	0 0%	0 0%

61. Secondary Outcome

Title	Serum Concentrations of Insulin Degludec
Description	This outcome measure is applicable for Insulin degludec and Insulin degludec/liraglutide arms. Serum samples from the Insulin degludec/liraglutide and Insulin degludec arms were assayed using population PK analysis. The maximum serum concentrations (Cmax) are summarised for the two arms.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Insulin Degludec
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.
Measure Participants	339	168
Geometric Mean (Geometric Coefficient of Variation) [pmol/L]	3583 (55.9)	4133 (52.8)

62. Secondary Outcome

Title	Plasma Concentration of Liraglutide
Description	This outcome measure is for Insulin degludec/liraglutide and liraglutide arms. Serum samples from the Insulin degludec/liraglutide and liraglutide arms were assayed using population PK analysis. The Cmax are summarised for the two arms.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Degludec/Liraglutide	Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.	Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
Measure Participants	339	165
Geometric Mean (Geometric Coefficient of Variation) [pmol/L]	9963 (50.4)	21602 (37)

Adverse Events

Time Frame	Weeks 0-30
Adverse Event Reporting Description	A TEAE was defined as an event that had 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. Results are based on SAS which included all participants who received at least one dose of insulin degludec/liraglutide, insulin degludec or liraglutide
Arm/Group Title	Insulin Degludec/Liraglutide		Insulin Degludec		Liraglutide
Arm/Group Description	Participants were to receive Insulin degludec/liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 dose steps (10 units insulin degludec and 0.36 mg liraglutide) initially. The dose was then adjusted twice weekly based on pre-breakfast self-measured plasma glucose (SMPG) target of 4.0-5.0 mmol/L. The maximum dose was 50 dose steps (50 units insulin degludec and 1.8 mg liraglutide). One dose step corresponded to 1 unit insulin degludec per 0.036 mg liraglutide.		Participants were to receive Insulin degludec subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 10 units insulin degludec initially. The dose was then adjusted twice weekly based on pre-breakfast SMPG target of 4.0-5.0 mmol/L. There was no maximum dose for Insulin degludec.		Participants were to receive liraglutide subcutaneous injection once daily in combination with metformin for 26 weeks. Participants received 0.6 mg initially. The dose was then escalated in weekly increments of 0.6 mg to reach a target dose of 1.8 mg. Liraglutide dose of 1.8 mg/day was continued for the remaining period of treatment."
All Cause Mortality
	Insulin Degludec/Liraglutide		Insulin Degludec		Liraglutide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/358 (0%)		0/175 (0%)		0/180 (0%)
Serious Adverse Events
	Insulin Degludec/Liraglutide		Insulin Degludec		Liraglutide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/358 (3.9%)		7/175 (4%)		14/180 (7.8%)
Cardiac disorders
Angina unstable	2/358 (0.6%)	2	1/175 (0.6%)	1	0/180 (0%)	0
Arteriosclerosis coronary artery	1/358 (0.3%)	1	0/175 (0%)	0	1/180 (0.6%)	1
Cardiac failure chronic	1/358 (0.3%)	1	0/175 (0%)	0	0/180 (0%)	0
Ear and labyrinth disorders
Deafness neurosensory	0/358 (0%)	0	1/175 (0.6%)	1	0/180 (0%)	0
Tinnitus	0/358 (0%)	0	1/175 (0.6%)	1	0/180 (0%)	0
Gastrointestinal disorders
Abdominal pain upper	1/358 (0.3%)	1	0/175 (0%)	0	0/180 (0%)	0
Chronic gastritis	0/358 (0%)	0	1/175 (0.6%)	1	0/180 (0%)	0
Gastric polyps	1/358 (0.3%)	1	0/175 (0%)	0	0/180 (0%)	0
Gastrooesophageal reflux disease	1/358 (0.3%)	1	0/175 (0%)	0	0/180 (0%)	0
Rectal polyp	1/358 (0.3%)	1	0/175 (0%)	0	0/180 (0%)	0
General disorders
Vascular stent stenosis	0/358 (0%)	0	0/175 (0%)	0	1/180 (0.6%)	1
Infections and infestations
Appendicitis perforated	0/358 (0%)	0	0/175 (0%)	0	1/180 (0.6%)	1
Endometritis	0/358 (0%)	0	0/175 (0%)	0	1/180 (0.6%)	1
Myelitis	1/358 (0.3%)	1	0/175 (0%)	0	0/180 (0%)	0
Injury, poisoning and procedural complications
Ankle fracture	1/358 (0.3%)	1	0/175 (0%)	0	0/180 (0%)	0
Clavicle fracture	0/358 (0%)	0	0/175 (0%)	0	1/180 (0.6%)	1
Foot fracture	0/358 (0%)	0	1/175 (0.6%)	1	0/180 (0%)	0
Ligament injury	1/358 (0.3%)	1	0/175 (0%)	0	0/180 (0%)	0
Metabolism and nutrition disorders
Diabetes mellitus inadequate control	0/358 (0%)	0	1/175 (0.6%)	1	0/180 (0%)	0
Musculoskeletal and connective tissue disorders
Dupuytren's contracture	0/358 (0%)	0	1/175 (0.6%)	1	0/180 (0%)	0
Intervertebral disc degeneration	1/358 (0.3%)	1	0/175 (0%)	0	0/180 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign breast neoplasm	0/358 (0%)	0	0/175 (0%)	0	1/180 (0.6%)	1
Lung neoplasm malignant	1/358 (0.3%)	1	0/175 (0%)	0	0/180 (0%)	0
Nervous system disorders
Cerebral infarction	1/358 (0.3%)	1	0/175 (0%)	0	3/180 (1.7%)	3
Ischaemic cerebral infarction	0/358 (0%)	0	0/175 (0%)	0	1/180 (0.6%)	1
Ischaemic stroke	1/358 (0.3%)	1	0/175 (0%)	0	0/180 (0%)	0
Reproductive system and breast disorders
Cervical dysplasia	0/358 (0%)	0	0/175 (0%)	0	1/180 (0.6%)	1
Respiratory, thoracic and mediastinal disorders
Bronchiectasis	0/358 (0%)	0	0/175 (0%)	0	1/180 (0.6%)	1
Skin and subcutaneous tissue disorders
Skin mass	1/358 (0.3%)	1	0/175 (0%)	0	0/180 (0%)	0
Surgical and medical procedures
Cataract operation	0/358 (0%)	0	1/175 (0.6%)	1	0/180 (0%)	0
Diabetes mellitus management	0/358 (0%)	0	0/175 (0%)	0	1/180 (0.6%)	1
Large intestinal polypectomy	0/358 (0%)	0	0/175 (0%)	0	1/180 (0.6%)	1
Mass excision	1/358 (0.3%)	1	0/175 (0%)	0	0/180 (0%)	0
Other (Not Including Serious) Adverse Events
	Insulin Degludec/Liraglutide		Insulin Degludec		Liraglutide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	161/358 (45%)		55/175 (31.4%)		98/180 (54.4%)
Eye disorders
Diabetic retinopathy	28/358 (7.8%)	28	6/175 (3.4%)	6	10/180 (5.6%)	10
Gastrointestinal disorders
Abdominal discomfort	1/358 (0.3%)	1	0/175 (0%)	0	9/180 (5%)	9
Diarrhoea	23/358 (6.4%)	31	3/175 (1.7%)	3	26/180 (14.4%)	41
Gastrointestinal disorder	1/358 (0.3%)	1	0/175 (0%)	0	10/180 (5.6%)	11
Nausea	14/358 (3.9%)	25	1/175 (0.6%)	1	21/180 (11.7%)	23
Infections and infestations
Nasopharyngitis	16/358 (4.5%)	20	9/175 (5.1%)	11	5/180 (2.8%)	7
Upper respiratory tract infection	66/358 (18.4%)	83	31/175 (17.7%)	34	18/180 (10%)	20
Investigations
Lipase increased	27/358 (7.5%)	30	5/175 (2.9%)	6	22/180 (12.2%)	22
Metabolism and nutrition disorders
Decreased appetite	13/358 (3.6%)	13	2/175 (1.1%)	2	26/180 (14.4%)	27
Hyperlipidaemia	16/358 (4.5%)	16	6/175 (3.4%)	6	10/180 (5.6%)	11

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