SCALE™ Insulin: Effect and Safety of Liraglutide 3.0 mg in Subjects With Overweight or Obesity and Type 2 Diabetes Mellitus Treated With Basal Insulin

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02963922
• Collaborator: (none)
• Enrollment: 396
• Locations: 54
• Arms: 2
• Actual Duration (Months): 19.6
• Patients Per Site: 7.3
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This trial is conducted globally. The aim of this trial is to investigate effect and safety of liraglutide 3.0 mg in subjects with overweight or obesity and type 2 diabetes mellitus treated with basal insulin.

Condition or Disease	Intervention/Treatment	Phase
Metabolism and Nutrition Disorder; Obesity	Drug: Liraglutide 3.0 mg; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 396 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Effect and Safety of Liraglutide 3.0 mg in Subjects With Overweight or Obesity and Type 2 Diabetes Mellitus Treated With Basal Insulin
• Actual Study Start Date: Feb 6, 2017
• Actual Primary Completion Date: Sep 10, 2018
• Actual Study Completion Date: Sep 25, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: liraglutide 3.0 mg	Drug: Liraglutide 3.0 mg; Injected subcutaneously (s.c., under the skin) once daily
Placebo Comparator: Placebo	Drug: Placebo; Injected subcutaneously (s.c., under the skin) once daily

Outcome Measures

Primary Outcome Measures

1. Change in Body Weight (%) [Week 0, week 56]

   Change in body weight from baseline (week 0) to week 56 was presented based on in-trial data and on-drug data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact. On-drug observation period: includes all time intervals in which participants are considered to be on treatment from the date of first trial product administration to 7 days (or 14 days for adverse events [AEs]) after the final trial product administration, excluding potential off-treatment time intervals triggered by at least 7 consecutive missed doses (or 14 consecutive missed doses for AEs).

2. Participants Losing at Least 5% of Baseline Body Weight [Week 56]

   The estimated percentage of participants losing at least 5% of baseline (week 0) body weight at week 56 was presented based on in-trial data and on-drug data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact. On-drug observation period: includes all time intervals in which participants are considered to be on treatment from the date of first trial product administration to 7 days (or 14 days for adverse events [AEs]) after the final trial product administration, excluding potential off-treatment time intervals triggered by at least 7 consecutive missed doses (or 14 consecutive missed doses for AEs).

Secondary Outcome Measures

1. Participants Losing More Than 10% of Baseline Body Weight at Week 56 [Week 56]

   The estimated percentage of participants losing more than 10% of baseline (week 0) body weight at week 56 was presented based on in-trial data and on-drug data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact. On-drug observation period: includes all time intervals in which participants are considered to be on treatment from the date of first trial product administration to 7 days (or 14 days for adverse events [AEs]) after the final trial product administration, excluding potential off-treatment time intervals triggered by at least 7 consecutive missed doses (or 14 consecutive missed doses for AEs).

2. Change in Waist Circumference [Week 0, week 56]

   Change in waist circumference from baseline (week 0) to week 56 was presented based on in-trial data and on-drug data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact. On-drug observation period: includes all time intervals in which participants are considered to be on treatment from the date of first trial product administration to 7 days (or 14 days for AEs) after the final trial product administration, excluding potential off-treatment time intervals triggered by at least 7 consecutive missed doses (or 14 consecutive missed doses for AEs).

3. Change in HbA1c [Week 0, week 56]

   Change in glycosylated haemoglobin (HbA1c) from baseline (week 0) to week 56 was presented based on in-trial data and on-drug data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact. On-drug observation period: includes all time intervals in which participants are considered to be on treatment from the date of first trial product administration to 7 days (or 14 days for AEs) after the final trial product administration, excluding potential off-treatment time intervals triggered by at least 7 consecutive missed doses (or 14 consecutive missed doses for AEs).

4. Change in FPG [Week 0, week 56]

   Change in fasting plasma glucose (FPG) from baseline (week 0) to week 56 was presented based on in-trial data and on-drug data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact. On-drug observation period: includes all time intervals in which participants are considered to be on treatment from the date of first trial product administration to 7 days (or 14 days for AEs) after the final trial product administration, excluding potential off-treatment time intervals triggered by at least 7 consecutive missed doses (or 14 consecutive missed doses for AEs).

5. Change in Short Form-36 (SF-36) v2.0 Acute, Physical Functioning Score [Week 0, week 56]

   SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ questionnaire measured the HRQoL on 8 domains on individual scale ranges. The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. A norm-based score of 50 corresponds to the mean score and 10 corresponds to the standard deviation of the 2009 U.S. general population. Change from baseline (week 0) in SF-36 physical functioning score was presented based on in-trial data and on-drug data. A positive change score indicates an improvement since baseline.

6. Change in Impact of Weight on Quality of Life-Lite for Clinical Trial Version (IWQoL-Lite for CT), Physical Function Domain (5-items) Score [Week 0, week 56]

   Change in IWQoL-Lite for CT physical function domain (5-items) score. IWQoL-Lite for CT is a modified version of an instrument designed to assess weight-related quality of life. The scores ranged between 0-100 where higher scores indicated a better quality of life. A positive change score indicates an improvement since baseline. The endpoint was presented based on in-trial data and on-drug data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact. On-drug observation period: includes all time intervals in which participants are considered to be on treatment from the date of first trial product administration to 7 days (or 14 days for AEs) after the final trial product administration, excluding potential off-treatment time intervals triggered by at least 7 consecutive missed doses (or 14 consecutive missed doses for AEs).

7. Change in Total Daily Insulin Dose (U) [Week 0, week 56]

   Change in total daily insulin dose from baseline (week 0) to week 56 was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.

8. Change in Total Daily Basal Insulin Dose (% of Pre-trial Dose in U) [Week 0, week 56]

   Change in total daily basal insulin dose from baseline (week 0) to week 56 was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.

9. Change in Total Daily Basal Insulin Dose (U/kg) [Week 0, week 56]

   Change in total daily basal insulin dose from baseline (week 0) to week 56 was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.

10. Change in Total Daily Insulin Dose (U/kg) [Week 0, week 56]

    Change in total daily insulin dose from baseline (week 0) to week 56 was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.

11. Change in 7-point SMPG Profile Mean Daytime Glucose Value [Week 0, week 56]

    Participants measured plasma glucose values using the blood glucose meter at 7 time points: before breakfast, 90 min after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 min after start of dinner and at bedtime. Change from baseline (week 0) to week 56 in 7-point self-measured plasma glucose (SMPG) profile mean daytime glucose value was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.

12. Change in sBP and dBP [Week 0, week 56]

    Change in systolic blood pressure (sBP) and diastolic blood pressure (dBP) from baseline (week 0) to week 56 was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.

13. Change in Lipids -Total Cholesterol, HDL, LDL, VLDL, Triglycerides and FFA [Week 0, week 56]

    Change in total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, very low density lipoprotein (VLDL) cholesterol, triglycerides and free fatty acids (FFA) from baseline (week 0) to week 56 was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.

14. Change in SF-36: Sub-domains [Week 0, week 56]

    SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ questionnaire measured the HRQoL on 8 domains on individual scale ranges. The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. A norm-based score of 50 corresponds to the mean score and 10 corresponds to the standard deviation of the 2009 U.S. general population. Change from baseline in the sub-domain scores was presented based on in-trial data. A positive change score indicates an improvement since baseline. Results are presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.

15. Change in SF-36: Physical Component Summary (PCS) [Week 0, week 56]

    Change in short form 36 v2.0 acute domain physical component summary (PCS) from baseline (week 0) to week 56 was presented based on in-trial data. SF-36v2™ questionnaire measured the HRQoL on 8 domains on individual scale ranges. It consists of 2 component summary measures that further summarize 8 health domain scales. The physical component summary (PCS) measure is derived from domain scales of physical functioning, role-physical, bodily pain, and general health. The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. A norm-based score of 50 corresponds to the mean score and 10 corresponds to the standard deviation of the 2009 U.S. general population. A positive change score indicates an improvement since baseline.

16. Change in SF-36: Mental Component Summary (MCS) [Week 0, week 56]

    Change in short form 36 v2.0 acute domain mental component summary (MCS) from baseline (week 0) to week 56 was presented based on in-trial data. SF- 36v2™ questionnaire measured the HRQoL on 8 domains on individual scale ranges. The mental component summary (MCS) measure is derived from domain scales of vitality, social functioning, role emotional and mental health. The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. A norm-based score of 50 corresponds to the mean score and 10 corresponds to the standard deviation of the 2009 U.S. general population. A positive change score indicates an improvement since baseline.

17. Change in IWQoL-Lite for CT: Pain/Discomfort Domain Score [Week 0, week 56]

    Change in IWQoL-Lite for CT pain and discomfort domain from baseline (week 0) to week 56 was presented based on in-trial data. IWQoL-Lite for CT is a modified version of an instrument designed to assess weight-related quality of life. The scores ranged between 0-100 where higher scores indicated a better quality of life. A positive change score indicates an improvement since baseline. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.

18. Change in IWQoL-Lite for CT: Psychosocial Domain Score [Week 0, week 56]

    Change in IWQoL-Lite for CT psychosocial domain from baseline (week 0) to week 56 was presented based on in-trial data. IWQoL-Lite for CT is a modified version of an instrument designed to assess weight-related quality of life. The scores ranged between 0-100 where higher scores indicated a better quality of life. A positive change score indicates an improvement since baseline. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.

19. Change in IWQoL-Lite for CT: Total Score [Week 0, week 56]

    Change in IWQoL-Lite for CT total score from baseline (week 0) to week 56 was presented based on in-trial data. IWQoL-Lite for CT is a modified version of an instrument designed to assess weight-related quality of life. The scores ranged between 0-100 where higher scores indicated a better quality of life. A positive change score indicates an improvement since baseline. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.

20. Weight Related Sign and Symptom (WRSS) Measure, Categorical Responses [Week 0, week 56]

    The WRSS measure is a questionnaire under development. The version applied in this study has 10 items that measure the presence and bothersomeness of 10 weight-related symptoms. Each item has a categorical part with answers on the following 5 possible levels: 'Never/Almost never', 'Rarely', 'Sometimes', 'Often' and 'Almost always/Always'. Number of participants in each category at baseline (week 0) and week 56 was presented. Scoring algorithm was not available prior to database lock and therefore it was decided and documented in the statistical analysis plan that WRSS total score was not to be calculated and analyzed.

21. Participants Who Achieved (Yes/no): HbA1c <7% and Weight Loss ≥5% [Week 56]

    Percentage of participants who achieved HbA1c <7% and weight loss ≥5% from baseline at week 56 was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.

22. Participants Who Achieved (Yes/no): HbA1c <7%, Weight Loss ≥5% and no Documented Symptomatic Hypoglycaemia [Week 56]

    Percentage of participants who achieved HbA1c <7%, weight loss ≥5% from baseline and no documented symptomatic hypoglycaemia at week 56 was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.

23. Participants Who Achieved (Yes/no): ≥4.3 T-score Points Increase From Baseline in SF-36 Acute Physical Functioning Score [Week 56]

    Percentage of participants who achieved ≥4.3 T-score points increase from baseline in SF-36 acute physical functioning score at week 56 was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.

24. Participants Who Achieved (Yes/no): ≥3.8 T-score Points Increase From Baseline in SF-36 Acute PCS [Week 56]

    Percentage of participants who achieved ≥3.8 T-score points increase from baseline in SF-36 acute PCS at week 56 was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.

25. Participants Who Achieved (Yes/no): ≥4.6 T-score Points Increase From Baseline in SF-36 Acute MCS [Week 56]

    Percentage of participants who achieved ≥4.6 T-score points increase from baseline in SF-36 acute MCS at week 56 was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.

26. Responder Definition Value for IWQoL-Lite for CT Physical Function Domain Score [Week 56]

    Percentage of participants who achieve responder definition value for IWQoL-Lite for CT physical function domain score was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.

27. Adverse Events (AEs) [Week 0 to week 56 + 30 days]

    An AE was defined as any untoward medical occurrence in a participant administered a medicinal product, and which does not necessarily have a causal relationship with this treatment. Number of AEs from randomisation to until the end of the post-treatment follow-up period (30 days). Results based on in-trial data was presented. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.

28. Number of Hypoglycaemic Episodes [Week 0 to week 56 + 30 days]

    Number of hypoglycaemic episodes was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.

29. Change in Physical Examination [Week -1, week 56]

    Physical examination parameters are categorised as abdomen; gastrointestinal system; cardiovascular system; central and peripheral nervous system; general appearance; head, eyes, ears, nose, throat (ENT) and 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 baseline (week -1) and week 56 was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.

30. Change in Resting Pulse [Week -1, week 56]

    Change from baseline (week -1) to week 56 in resting pulse was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.

31. Change in Electrocardiogram (ECG) [Week -1, week 56]

    The ECGs were interpreted by the investigator at baseline (week -1) and week 56 and categorised as normal, abnormal NCS or abnormal CS. Number of participants in each ECG category at baseline and week 56 were presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.

32. Change in Laboratory Measurements (Haematology) - Haemoglobin [Week 0, week 56]

    Change from baseline (week 0) to week 56 in haemoglobin was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.

33. Change in Laboratory Measurements (Haematology) - Haematocrit [Week 0, week 56]

    Change from baseline (week 0) to week 56 in Haematocrit was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.

34. Change in Laboratory Measurements (Haematology) - Erythrocytes [Week 0, week 56]

    Change from baseline (week 0) to week 56 in erythrocytes was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.

35. Change in Laboratory Measurements (Haematology) - Thrombocytes, Leukocytes [Week 0, week 56]

    Change from baseline (week 0) to week 56 in thrombocytes and leukocytes was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.

36. Change in Laboratory Parameters (Biochemistry) - Albumin [Week 0, week 56]

    Change from baseline (week 0) to week 56 in albumin was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.

37. Change in Laboratory Parameters (Biochemistry) - Alkaline Phosphatase, Alanine Aminotransferase, Amylase, Aspartate Aminotransferase and Lipase [Week 0, week 56]

    Change from baseline (week 0) to week 56 in alkaline phosphatase, alanine aminotransferase, amylase, aspartate aminotransferase and lipase was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.

38. Change in Laboratory Parameters (Biochemistry) - Bicarbonate, Total Calcium, Potassium, Sodium and Urea [Week 0, week 56]

    Change from baseline (week 0) to week 56 in bicarbonate, total calcium, potassium, sodium and urea was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.

39. Change in Laboratory Parameters (Biochemistry) - Total Bilirubin and Creatinine [Week 0, week 56]

    Change from baseline (week 0) to week 56 in total bilirubin and creatinine was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.

40. Change in Laboratory Parameters (Biochemistry) - High Sensitive C-reactive Protein [Week 0, week 56]

    Change from baseline (week 0) to week 56 in high sensitive C-reactive protein was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.

41. Change in Laboratory Parameters (Biochemistry) - eGFR [Week 0, week 56]

    Change from baseline (week 0) to week 56 in estimated GFR serum using Modification of Diet in Renal Disease (MDRD) formula was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.

42. Change in Laboratory Parameters (Biochemistry) - Uric Acid [Week 0, week 56]

    Change from baseline (week 0) to week 56 in uric acid was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.

43. Change in Laboratory Parameters (Biochemistry) - Calcitonin [Week 0, week 56]

    Change from baseline (week 0) to week 56 in calcitonin was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.

44. Change in Laboratory Parameters (Biochemistry) - Thyroid Stimulating Hormone [Week 0, week 56]

    Change from baseline (week 0) to week 56 in thyroid stimulating hormone was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.

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 - Diagnosed with type 2 diabetes mellitus - Treatment with up to 2 OADs (oral anti-diabetic) (metformin, glitazone, SGLT-2 inhibitor (sodium-glucose cotransporter-2 inhibitors) or sulphonylurea) - Stable treatment with basal insulin according to its label (no requirement of minimum or maximum dose) for at least 90 days prior to screening, as judged by the investigator - HbA1c (glycosylated haemoglobin) 6.0-10.0% (both inclusive) - BMI (body mass index) equal to or above 27 kg/m^2 - Age at least 18 years at the time of signing informed consent Exclusion Criteria: - Diagnosis of type 1 diabetes - Known hypoglycaemic unawareness as indicated by the investigator according to Clarke's questionnaire question 8 (see Section 8.2.3) - Recurrent severe hypoglycaemic episodes within the last year as judged by the investigator

• Unable or unwilling to perform self-monitoring of plasma glucose according to the protocol and to keep a diabetes diary - Treatment with any hypoglycaemic medications other than OADs and basal insulin within the past 90 days prior to screening - Treatment with a DPP-IV (dipeptidyl peptidase-4) inhibitor within the past 90 days prior to screening - Recent history of cardiovascular disease (myocardial infarction or stroke within the past 6 months), severe congestive heart failure (NYHA class III, IV), or second degree or greater heart block - Personal or family history of Medullary Thyroid Carcinoma (MTC) or Multiple Endocrine Neoplasia type 2 (MEN2) - Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method (adequate contraceptive measure as required by local regulation or practice) - For Germany: Only highly effective methods of birth control are accepted (i.e. one that results in less than 1% per year failure rate when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intrauterine device), or sexual abstinence or vasectomised partner - Use in past 90 days of medications known to induce significant weight loss (e.g., prescription weight loss medications) or weight gain (e.g., chronic use of oral steroids, second generation antipsychotics) - History of pancreatitis (acute or chronic) - History of major depressive disorder within the past 2 years - Any lifetime history of a suicide attempt - Inadequately treated blood pressure defined as Grade 3 hypertension or higher (Systolic above or equal to 180 mmHg or diastolic above or equal to110 mmHg). - History of malignancy (except for non-melanoma skin cancer) within the past 5 years

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Birmingham	Alabama	United States	35294
2	Novo Nordisk Investigational Site	Concord	California	United States	94520
3	Novo Nordisk Investigational Site	Fresno	California	United States	93720
4	Novo Nordisk Investigational Site	Jacksonville	Florida	United States	32205
5	Novo Nordisk Investigational Site	Plantation	Florida	United States	33324
6	Novo Nordisk Investigational Site	Roswell	Georgia	United States	30076
7	Novo Nordisk Investigational Site	Honolulu	Hawaii	United States	96814
8	Novo Nordisk Investigational Site	Chicago	Illinois	United States	60607
9	Novo Nordisk Investigational Site	Louisville	Kentucky	United States	40213
10	Novo Nordisk Investigational Site	North Dartmouth	Massachusetts	United States	02747
11	Novo Nordisk Investigational Site	Minneapolis	Minnesota	United States	55416
12	Novo Nordisk Investigational Site	Butte	Montana	United States	59701
13	Novo Nordisk Investigational Site	Albany	New York	United States	12206
14	Novo Nordisk Investigational Site	Wilmington	North Carolina	United States	28401
15	Novo Nordisk Investigational Site	Austin	Texas	United States	78731
16	Novo Nordisk Investigational Site	Austin	Texas	United States	78749
17	Novo Nordisk Investigational Site	Dallas	Texas	United States	75230
18	Novo Nordisk Investigational Site	Dallas	Texas	United States	75231
19	Novo Nordisk Investigational Site	Winchester	Virginia	United States	22601-3834
20	Novo Nordisk Investigational Site	Calgary	Alberta	Canada	T2V 4J2
21	Novo Nordisk Investigational Site	Edmonton	Alberta	Canada	T6H 2L4
22	Novo Nordisk Investigational Site	Halifax	Nova Scotia	Canada	B3H 2Y9
23	Novo Nordisk Investigational Site	Hamilton	Ontario	Canada	L8L 5G8
24	Novo Nordisk Investigational Site	London	Ontario	Canada	N6A 5B7
25	Novo Nordisk Investigational Site	Toronto	Ontario	Canada	M6G 1M2
26	Novo Nordisk Investigational Site	Waterloo	Ontario	Canada	N2J 1C4
27	Novo Nordisk Investigational Site	Quebec		Canada	G1V 4G5
28	Novo Nordisk Investigational Site	Dresden		Germany	01307
29	Novo Nordisk Investigational Site	Essen		Germany	45219
30	Novo Nordisk Investigational Site	Falkensee		Germany	14612
31	Novo Nordisk Investigational Site	Hamburg		Germany	22607
32	Novo Nordisk Investigational Site	Leipzig		Germany	04103
33	Novo Nordisk Investigational Site	Münster		Germany	48145
34	Novo Nordisk Investigational Site	Rehlingen-Siersburg		Germany	66780
35	Novo Nordisk Investigational Site	Saint Ingbert-Oberwürzbach		Germany	66386
36	Novo Nordisk Investigational Site	Haifa		Israel	35152
37	Novo Nordisk Investigational Site	Jerusalem		Israel	91120
38	Novo Nordisk Investigational Site	Kfar Saba		Israel	44281
39	Novo Nordisk Investigational Site	Petah-Tikva		Israel	49372
40	Novo Nordisk Investigational Site	Tel Hashomer		Israel	52621
41	Novo Nordisk Investigational Site	Tel-Aviv		Israel	64239
42	Novo Nordisk Investigational Site	Bologna		Italy	40138
43	Novo Nordisk Investigational Site	Napoli		Italy	80131
44	Novo Nordisk Investigational Site	Palermo		Italy	90127
45	Novo Nordisk Investigational Site	Rome		Italy	00168
46	Novo Nordisk Investigational Site	Guadalajara	Jalisco	Mexico	44600
47	Novo Nordisk Investigational Site	Monterrey	Nuevo León	Mexico	64620
48	Novo Nordisk Investigational Site	Ankara		Turkey	06500
49	Novo Nordisk Investigational Site	Antalya		Turkey	07058
50	Novo Nordisk Investigational Site	Istanbul		Turkey	34096
51	Novo Nordisk Investigational Site	Istanbul		Turkey	34303
52	Novo Nordisk Investigational Site	Istanbul		Turkey	34371
53	Novo Nordisk Investigational Site	Istanbul		Turkey	34890
54	Novo Nordisk Investigational Site	Izmir		Turkey	35340

Sponsors and Collaborators

• Novo Nordisk A/S

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Feb 18, 2019
• Statistical Analysis Plan - Feb 18, 2019

More Information

Publications

None provided.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT02963922
• Other Study ID Numbers: NN8022-4272; U1111-1177-4903; 2015-005619-33
• First Posted: Nov 15, 2016
• Last Update Posted: Mar 30, 2020
• Last Verified: Mar 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Diabetes Mellitus; Obesity; Diabetes Mellitus, Type 2; Nutrition Disorders; Overweight; Liraglutide

Study Results

Participant Flow

Recruitment Details	The trial was conducted at 53 sites in Canada (7), Germany (7), Israel (6), Italy (4), Mexico (2), Turkey (7) and United States (20).
Pre-assignment Detail	Participants were randomised in a 1:1 manner to receive either liraglutide or placebo as an adjunct to a reduced-calorie diet and increased physical activity as part of a comprehensive lifestyle intervention program.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 milligrams (mg) liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Period Title: Overall Study
STARTED	198	198
COMPLETED	166	168
NOT COMPLETED	32	30

Baseline Characteristics

Arm/Group Title	Liraglutide 3.0 mg	Placebo	Total
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.	Total of all reporting groups
Overall Participants	198	198	396
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.9 (11.3)	57.6 (10.4)	56.8 (10.9)
Sex: Female, Male (Count of Participants)
Female	108 54.5%	99 50%	207 52.3%
Male	90 45.5%	99 50%	189 47.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	43 21.7%	29 14.6%	72 18.2%
Not Hispanic or Latino	155 78.3%	169 85.4%	324 81.8%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	2 1%	0 0%	2 0.5%
Asian	3 1.5%	5 2.5%	8 2%
Black or African American	17 8.6%	11 5.6%	28 7.1%
Native Hawaiian or Other Pacific Islander	2 1%	0 0%	2 0.5%
White	174 87.9%	180 90.9%	354 89.4%
Other	0 0%	2 1%	2 0.5%
Body weight (Kilograms (kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Kilograms (kg)]	100.6 (20.8)	98.9 (19.9)	99.7 (20.3)

Outcome Measures

1. Primary Outcome

Title	Change in Body Weight (%)
Description	Change in body weight from baseline (week 0) to week 56 was presented based on in-trial data and on-drug data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact. On-drug observation period: includes all time intervals in which participants are considered to be on treatment from the date of first trial product administration to 7 days (or 14 days for adverse events [AEs]) after the final trial product administration, excluding potential off-treatment time intervals triggered by at least 7 consecutive missed doses (or 14 consecutive missed doses for AEs).
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	198	198
In-trial observation period	-6.0 (6.0)	-1.5 (5.4)
On-drug observation period	-6.5 (5.8)	-1.7 (5.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide 3.0 mg, Placebo
	Comments	Analysis of in-trial data with missing observations imputed from the placebo arm based on a jump to reference multiple (x100) imputation approach. Week 56 responses were analysed using an analysis of covariance model with treatment, body mass index (BMI) groups and sex as factors and baseline body weight as covariate.
	Type of Statistical Test	Superiority
	Comments	The treatment policy estimand evaluated the treatment effect (liraglutide 3.0 mg vs placebo) at week 56 for all randomised participants regardless of premature discontinuation of trial product.
Statistical Test of Hypothesis	p-Value	< .0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-4.32
	Confidence Interval	(2-Sided) 95%; -5.48 to -3.16
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.59
	Estimation Comments	Liraglutide 3.0 mg - placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Liraglutide 3.0 mg, Placebo
	Comments	Analysis of on-drug before first drug discontinuation date using a mixed model for repeated measurements with treatment, BMI groups and sex as factors and baseline body weight as covariate, all nested within visit.
	Type of Statistical Test	Superiority
	Comments	The hypothetical estimand evaluated the treatment effect (liraglutide 3.0 mg vs placebo) for all randomised participants assuming that all participants remained on trial product (on-treatment principle).
Statistical Test of Hypothesis	p-Value	< .0001
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-5.10
	Confidence Interval	(2-Sided) 95%; -6.30 to -3.91
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.61
	Estimation Comments	Liraglutide 3.0 mg - placebo

2. Primary Outcome

Title	Participants Losing at Least 5% of Baseline Body Weight
Description	The estimated percentage of participants losing at least 5% of baseline (week 0) body weight at week 56 was presented based on in-trial data and on-drug data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact. On-drug observation period: includes all time intervals in which participants are considered to be on treatment from the date of first trial product administration to 7 days (or 14 days for adverse events [AEs]) after the final trial product administration, excluding potential off-treatment time intervals triggered by at least 7 consecutive missed doses (or 14 consecutive missed doses for AEs).
Time Frame	Week 56

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	198	198
In-trial observation period	51.80 26.2%	23.98 12.1%
On-drug observation period	56.92 28.7%	21.83 11%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Liraglutide 3.0 mg, Placebo
	Comments	Analysis of in-trial data with missing observations imputed from the placebo arm based on a jump to reference multiple (x100) imputation approach. Week 56 responses were analysed using a logistic regression model with treatment, BMI groups and sex as factors and baseline body weight as covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.41
	Confidence Interval	(2-Sided) 95%; 2.19 to 5.31
	Parameter Dispersion	Type: Value:
	Estimation Comments	Liraglutide 3.0 mg/Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Liraglutide 3.0 mg, Placebo
	Comments	Analysis of on-drug before first drug discontinuation date using a mixed model for repeated measurements with treatment, BMI groups and sex as factors and baseline body weight as covariate, all nested within visit. The MMRM was used to classify responders and analysed with a logistic regression with treatment as the only factor.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Mixed model for repeated measurements
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	4.73
	Confidence Interval	(2-Sided) 95%; 3.04 to 7.36
	Parameter Dispersion	Type: Value:
	Estimation Comments	Liraglutide 3.0 mg/Placebo

3. Secondary Outcome

Title	Participants Losing More Than 10% of Baseline Body Weight at Week 56
Description	The estimated percentage of participants losing more than 10% of baseline (week 0) body weight at week 56 was presented based on in-trial data and on-drug data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact. On-drug observation period: includes all time intervals in which participants are considered to be on treatment from the date of first trial product administration to 7 days (or 14 days for adverse events [AEs]) after the final trial product administration, excluding potential off-treatment time intervals triggered by at least 7 consecutive missed doses (or 14 consecutive missed doses for AEs).
Time Frame	Week 56

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	198	198
In-trial observation period	22.77 11.5%	6.55 3.3%
On-drug observation period	22.56 11.4%	5.58 2.8%

4. Secondary Outcome

Title	Change in Waist Circumference
Description	Change in waist circumference from baseline (week 0) to week 56 was presented based on in-trial data and on-drug data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact. On-drug observation period: includes all time intervals in which participants are considered to be on treatment from the date of first trial product administration to 7 days (or 14 days for AEs) after the final trial product administration, excluding potential off-treatment time intervals triggered by at least 7 consecutive missed doses (or 14 consecutive missed doses for AEs).
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	198	198
In-trial observation period	-5.40 (6.06)	-2.60 (5.72)
On-drug observation period	-5.71 (6.05)	-2.78 (5.63)

5. Secondary Outcome

Title	Change in HbA1c
Description	Change in glycosylated haemoglobin (HbA1c) from baseline (week 0) to week 56 was presented based on in-trial data and on-drug data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact. On-drug observation period: includes all time intervals in which participants are considered to be on treatment from the date of first trial product administration to 7 days (or 14 days for AEs) after the final trial product administration, excluding potential off-treatment time intervals triggered by at least 7 consecutive missed doses (or 14 consecutive missed doses for AEs).
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	198	198
In-trial observation period	-1.1 (1.2)	-0.5 (1.2)
On-drug observation period	-1.2 (1.1)	-0.7 (1.0)

6. Secondary Outcome

Title	Change in FPG
Description	Change in fasting plasma glucose (FPG) from baseline (week 0) to week 56 was presented based on in-trial data and on-drug data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact. On-drug observation period: includes all time intervals in which participants are considered to be on treatment from the date of first trial product administration to 7 days (or 14 days for AEs) after the final trial product administration, excluding potential off-treatment time intervals triggered by at least 7 consecutive missed doses (or 14 consecutive missed doses for AEs).
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	198	198
In-trial observation period	-0.91 (3.13)	-0.68 (3.04)
On-drug observation period	-1.05 (3.08)	-0.96 (2.68)

7. Secondary Outcome

Title	Change in Short Form-36 (SF-36) v2.0 Acute, Physical Functioning Score
Description	SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ questionnaire measured the HRQoL on 8 domains on individual scale ranges. The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. A norm-based score of 50 corresponds to the mean score and 10 corresponds to the standard deviation of the 2009 U.S. general population. Change from baseline (week 0) in SF-36 physical functioning score was presented based on in-trial data and on-drug data. A positive change score indicates an improvement since baseline.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	198	198
In-trial observation period	2.5 (7.9)	2.6 (7.3)
On-drug observation period	2.9 (7.8)	2.5 (7.1)

8. Secondary Outcome

Title	Change in Impact of Weight on Quality of Life-Lite for Clinical Trial Version (IWQoL-Lite for CT), Physical Function Domain (5-items) Score
Description	Change in IWQoL-Lite for CT physical function domain (5-items) score. IWQoL-Lite for CT is a modified version of an instrument designed to assess weight-related quality of life. The scores ranged between 0-100 where higher scores indicated a better quality of life. A positive change score indicates an improvement since baseline. The endpoint was presented based on in-trial data and on-drug data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact. On-drug observation period: includes all time intervals in which participants are considered to be on treatment from the date of first trial product administration to 7 days (or 14 days for AEs) after the final trial product administration, excluding potential off-treatment time intervals triggered by at least 7 consecutive missed doses (or 14 consecutive missed doses for AEs).
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	198	198
In-trial observation period	7.3 (22.5)	6.8 (21.5)
On-drug observation period	8.2 (20.9)	6.5 (21.8)

9. Secondary Outcome

Title	Change in Total Daily Insulin Dose (U)
Description	Change in total daily insulin dose from baseline (week 0) to week 56 was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	198	198
Mean (Standard Deviation) [Units of insulin dose (U)]	3 (30)	18 (38)

10. Secondary Outcome

Title	Change in Total Daily Basal Insulin Dose (% of Pre-trial Dose in U)
Description	Change in total daily basal insulin dose from baseline (week 0) to week 56 was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	198	198
Mean (Standard Deviation) [Percentage change]	19 (121)	64 (139)

11. Secondary Outcome

Title	Change in Total Daily Basal Insulin Dose (U/kg)
Description	Change in total daily basal insulin dose from baseline (week 0) to week 56 was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	198	198
Mean (Standard Deviation) [Units of insulin dose per kilogram(U/kg)]	0.05 (0.33)	0.15 (0.30)

12. Secondary Outcome

Title	Change in Total Daily Insulin Dose (U/kg)
Description	Change in total daily insulin dose from baseline (week 0) to week 56 was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	198	198
Mean (Standard Deviation) [U/kg]	0.05 (0.33)	0.18 (0.37)

13. Secondary Outcome

Title	Change in 7-point SMPG Profile Mean Daytime Glucose Value
Description	Participants measured plasma glucose values using the blood glucose meter at 7 time points: before breakfast, 90 min after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 min after start of dinner and at bedtime. Change from baseline (week 0) to week 56 in 7-point self-measured plasma glucose (SMPG) profile mean daytime glucose value was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	198	198
Mean (Standard Deviation) [mmol/L]	-2.2 (2.6)	-1.6 (2.8)

14. Secondary Outcome

Title	Change in sBP and dBP
Description	Change in systolic blood pressure (sBP) and diastolic blood pressure (dBP) from baseline (week 0) to week 56 was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	198	198
sBP	-6 (14)	-2 (15)
dBP	-3 (9)	-1 (9)

15. Secondary Outcome

Title	Change in Lipids -Total Cholesterol, HDL, LDL, VLDL, Triglycerides and FFA
Description	Change in total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, very low density lipoprotein (VLDL) cholesterol, triglycerides and free fatty acids (FFA) from baseline (week 0) to week 56 was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	198	198
Total cholesterol	-0.12 (0.82)	0.04 (0.69)
HDL cholesterol	0.05 (0.17)	0.03 (0.17)
LDL cholesterol	-0.08 (0.72)	0.05 (0.57)
VLDL cholesterol	-0.09 (0.35)	-0.04 (0.33)
Triglycerides	-0.21 (0.89)	-0.08 (0.80)
Free fatty acids	-0.10 (0.27)	-0.06 (0.34)

16. Secondary Outcome

Title	Change in SF-36: Sub-domains
Description	SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ questionnaire measured the HRQoL on 8 domains on individual scale ranges. The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. A norm-based score of 50 corresponds to the mean score and 10 corresponds to the standard deviation of the 2009 U.S. general population. Change from baseline in the sub-domain scores was presented based on in-trial data. A positive change score indicates an improvement since baseline. Results are presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	198	198
Bodily Pain	1.2 (8.3)	1.2 (9.1)
General Health	1.9 (7.8)	0.3 (7.7)
Physical Functioning	2.5 (7.9)	2.6 (7.3)
Role-physical	0.8 (7.7)	0.9 (8.0)
Role Lim Emotion Prob	-1.2 (8.1)	-0.3 (8.2)
Mental Health	-1.1 (8.6)	-1.1 (7.5)
Social Functioning	-0.7 (7.7)	-0.6 (6.3)
Vitality	1.0 (8.0)	-0.0 (7.7)

17. Secondary Outcome

Title	Change in SF-36: Physical Component Summary (PCS)
Description	Change in short form 36 v2.0 acute domain physical component summary (PCS) from baseline (week 0) to week 56 was presented based on in-trial data. SF-36v2™ questionnaire measured the HRQoL on 8 domains on individual scale ranges. It consists of 2 component summary measures that further summarize 8 health domain scales. The physical component summary (PCS) measure is derived from domain scales of physical functioning, role-physical, bodily pain, and general health. The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. A norm-based score of 50 corresponds to the mean score and 10 corresponds to the standard deviation of the 2009 U.S. general population. A positive change score indicates an improvement since baseline.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	198	198
Mean (Standard Deviation) [Score on a scale]	2.7 (7.5)	2.2 (7.2)

18. Secondary Outcome

Title	Change in SF-36: Mental Component Summary (MCS)
Description	Change in short form 36 v2.0 acute domain mental component summary (MCS) from baseline (week 0) to week 56 was presented based on in-trial data. SF- 36v2™ questionnaire measured the HRQoL on 8 domains on individual scale ranges. The mental component summary (MCS) measure is derived from domain scales of vitality, social functioning, role emotional and mental health. The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. A norm-based score of 50 corresponds to the mean score and 10 corresponds to the standard deviation of the 2009 U.S. general population. A positive change score indicates an improvement since baseline.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	198	198
Mean (Standard Deviation) [Score on a scale]	-1.9 (7.9)	-1.7 (6.8)

19. Secondary Outcome

Title	Change in IWQoL-Lite for CT: Pain/Discomfort Domain Score
Description	Change in IWQoL-Lite for CT pain and discomfort domain from baseline (week 0) to week 56 was presented based on in-trial data. IWQoL-Lite for CT is a modified version of an instrument designed to assess weight-related quality of life. The scores ranged between 0-100 where higher scores indicated a better quality of life. A positive change score indicates an improvement since baseline. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	198	198
Mean (Standard Deviation) [Score on a scale]	4.0 (22.1)	4.6 (23.1)

20. Secondary Outcome

Title	Change in IWQoL-Lite for CT: Psychosocial Domain Score
Description	Change in IWQoL-Lite for CT psychosocial domain from baseline (week 0) to week 56 was presented based on in-trial data. IWQoL-Lite for CT is a modified version of an instrument designed to assess weight-related quality of life. The scores ranged between 0-100 where higher scores indicated a better quality of life. A positive change score indicates an improvement since baseline. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	198	198
Mean (Standard Deviation) [Score on a scale]	5.4 (18.4)	4.0 (16.7)

21. Secondary Outcome

Title	Change in IWQoL-Lite for CT: Total Score
Description	Change in IWQoL-Lite for CT total score from baseline (week 0) to week 56 was presented based on in-trial data. IWQoL-Lite for CT is a modified version of an instrument designed to assess weight-related quality of life. The scores ranged between 0-100 where higher scores indicated a better quality of life. A positive change score indicates an improvement since baseline. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	198	198
Mean (Standard Deviation) [Score on a scale]	5.7 (17.6)	4.8 (16.6)

22. Secondary Outcome

Title	Weight Related Sign and Symptom (WRSS) Measure, Categorical Responses
Description	The WRSS measure is a questionnaire under development. The version applied in this study has 10 items that measure the presence and bothersomeness of 10 weight-related symptoms. Each item has a categorical part with answers on the following 5 possible levels: 'Never/Almost never', 'Rarely', 'Sometimes', 'Often' and 'Almost always/Always'. Number of participants in each category at baseline (week 0) and week 56 was presented. Scoring algorithm was not available prior to database lock and therefore it was decided and documented in the statistical analysis plan that WRSS total score was not to be calculated and analyzed.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomised participants. "Number analyzed"=participants with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	198	198
Almost always/Always	11 5.6%	5 2.5%
Never/Almost never	74 37.4%	85 42.9%
Often	17 8.6%	18 9.1%
Rarely	47 23.7%	42 21.2%
Sometimes	49 24.7%	46 23.2%
Almost always/Always	6 3%	5 2.5%
Never/Almost never	95 48%	75 37.9%
Often	12 6.1%	17 8.6%
Rarely	35 17.7%	39 19.7%
Sometimes	39 19.7%	52 26.3%
Almost always/Always	0 0%	0 0%
Never/Almost never	131 66.2%	140 70.7%
Often	3 1.5%	3 1.5%
Rarely	45 22.7%	32 16.2%
Sometimes	19 9.6%	21 10.6%
Almost always/Always	1 0.5%	1 0.5%
Never/Almost never	137 69.2%	111 56.1%
Often	5 2.5%	3 1.5%
Rarely	28 14.1%	46 23.2%
Sometimes	16 8.1%	27 13.6%
Almost always/Always	8 4%	9 4.5%
Never/Almost never	106 53.5%	109 55.1%
Often	13 6.6%	16 8.1%
Rarely	34 17.2%	31 15.7%
Sometimes	37 18.7%	31 15.7%
Almost always/Always	2 1%	8 4%
Never/Almost never	92 46.5%	87 43.9%
Often	12 6.1%	13 6.6%
Rarely	42 21.2%	47 23.7%
Sometimes	39 19.7%	33 16.7%
Almost always/Always	8 4%	8 4%
Never/Almost never	119 60.1%	121 61.1%
Often	13 6.6%	13 6.6%
Rarely	35 17.7%	32 16.2%
Sometimes	23 11.6%	22 11.1%
Almost always/Always	6 3%	11 5.6%
Never/Almost never	105 53%	109 55.1%
Often	18 9.1%	11 5.6%
Rarely	34 17.2%	32 16.2%
Sometimes	24 12.1%	25 12.6%
Almost always/Always	2 1%	5 2.5%
Never/Almost never	101 51%	104 52.5%
Often	15 7.6%	14 7.1%
Rarely	40 20.2%	38 19.2%
Sometimes	40 20.2%	35 17.7%
Almost always/Always	1 0.5%	5 2.5%
Never/Almost never	98 49.5%	92 46.5%
Often	7 3.5%	16 8.1%
Rarely	51 25.8%	48 24.2%
Sometimes	30 15.2%	27 13.6%
Almost always/Always	2 1%	8 4%
Never/Almost never	73 36.9%	78 39.4%
Often	22 11.1%	14 7.1%
Rarely	56 28.3%	47 23.7%
Sometimes	45 22.7%	49 24.7%
Almost always/Always	3 1.5%	4 2%
Never/Almost never	77 38.9%	65 32.8%
Often	15 7.6%	19 9.6%
Rarely	57 28.8%	56 28.3%
Sometimes	35 17.7%	44 22.2%
Almost always/Always	5 2.5%	7 3.5%
Never/Almost never	114 57.6%	108 54.5%
Often	17 8.6%	12 6.1%
Rarely	34 17.2%	31 15.7%
Sometimes	28 14.1%	38 19.2%
Almost always/Always	2 1%	7 3.5%
Never/Almost never	106 53.5%	88 44.4%
Often	15 7.6%	14 7.1%
Rarely	29 14.6%	39 19.7%
Sometimes	35 17.7%	40 20.2%
Almost always/Always	6 3%	4 2%
Never/Almost never	119 60.1%	111 56.1%
Often	11 5.6%	10 5.1%
Rarely	30 15.2%	42 21.2%
Sometimes	32 16.2%	29 14.6%
Almost always/Always	6 3%	3 1.5%
Never/Almost never	104 52.5%	98 49.5%
Often	15 7.6%	14 7.1%
Rarely	38 19.2%	33 16.7%
Sometimes	24 12.1%	40 20.2%
Almost always/Always	8 4%	6 3%
Never/Almost never	96 48.5%	98 49.5%
Often	13 6.6%	8 4%
Rarely	49 24.7%	40 20.2%
Sometimes	32 16.2%	44 22.2%
Almost always/Always	5 2.5%	4 2%
Never/Almost never	93 47%	86 43.4%
Often	13 6.6%	11 5.6%
Rarely	47 23.7%	45 22.7%
Sometimes	29 14.6%	42 21.2%
Almost always/Always	0 0%	2 1%
Never/Almost never	102 51.5%	90 45.5%
Often	19 9.6%	12 6.1%
Rarely	46 23.2%	42 21.2%
Sometimes	31 15.7%	50 25.3%
Almost always/Always	0 0%	4 2%
Never/Almost never	82 41.4%	77 38.9%
Often	16 8.1%	16 8.1%
Rarely	49 24.7%	50 25.3%
Sometimes	40 20.2%	41 20.7%

23. Secondary Outcome

Title	Participants Who Achieved (Yes/no): HbA1c <7% and Weight Loss ≥5%
Description	Percentage of participants who achieved HbA1c <7% and weight loss ≥5% from baseline at week 56 was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Time Frame	Week 56

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomised participants.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	198	198
Number [Percentage of participants]	39.9 20.2%	13.6 6.9%

24. Secondary Outcome

Title	Participants Who Achieved (Yes/no): HbA1c <7%, Weight Loss ≥5% and no Documented Symptomatic Hypoglycaemia
Description	Percentage of participants who achieved HbA1c <7%, weight loss ≥5% from baseline and no documented symptomatic hypoglycaemia at week 56 was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Time Frame	Week 56

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomised participants.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	198	198
Number [Percentage of participants]	10.1 5.1%	3.5 1.8%

25. Secondary Outcome

Title	Participants Who Achieved (Yes/no): ≥4.3 T-score Points Increase From Baseline in SF-36 Acute Physical Functioning Score
Description	Percentage of participants who achieved ≥4.3 T-score points increase from baseline in SF-36 acute physical functioning score at week 56 was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Time Frame	Week 56

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomised participants.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	198	198
Number [Percentage of participants]	28.8 14.5%	26.3 13.3%

26. Secondary Outcome

Title	Participants Who Achieved (Yes/no): ≥3.8 T-score Points Increase From Baseline in SF-36 Acute PCS
Description	Percentage of participants who achieved ≥3.8 T-score points increase from baseline in SF-36 acute PCS at week 56 was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Time Frame	Week 56

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomised participants.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	198	198
Number [Percentage of participants]	37.9 19.1%	31.3 15.8%

27. Secondary Outcome

Title	Participants Who Achieved (Yes/no): ≥4.6 T-score Points Increase From Baseline in SF-36 Acute MCS
Description	Percentage of participants who achieved ≥4.6 T-score points increase from baseline in SF-36 acute MCS at week 56 was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Time Frame	Week 56

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomised participants.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	198	198
Number [Percentage of participants]	14.6 7.4%	11.6 5.9%

28. Secondary Outcome

Title	Responder Definition Value for IWQoL-Lite for CT Physical Function Domain Score
Description	Percentage of participants who achieve responder definition value for IWQoL-Lite for CT physical function domain score was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Time Frame	Week 56

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomised participants.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	198	198
Number [Percentage of participants]	25.3 12.8%	24.2 12.2%

29. Secondary Outcome

Title	Adverse Events (AEs)
Description	An AE was defined as any untoward medical occurrence in a participant administered a medicinal product, and which does not necessarily have a causal relationship with this treatment. Number of AEs from randomisation to until the end of the post-treatment follow-up period (30 days). Results based on in-trial data was presented. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Time Frame	Week 0 to week 56 + 30 days

Outcome Measure Data

Analysis Population Description

Safety analysis set (SAS) included all randomised participants exposed to at least one dose of trial drug.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	195	197
Number [Adverse events]	1223	1148

30. Secondary Outcome

Title	Number of Hypoglycaemic Episodes
Description	Number of hypoglycaemic episodes was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Time Frame	Week 0 to week 56 + 30 days

Outcome Measure Data

Analysis Population Description

SAS included all randomised participants exposed to at least one dose of trial drug.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	195	197
Number [Hypoglycaemic episodes]	1538	1973

31. Secondary Outcome

Title	Change in Physical Examination
Description	Physical examination parameters are categorised as abdomen; gastrointestinal system; cardiovascular system; central and peripheral nervous system; general appearance; head, eyes, ears, nose, throat (ENT) and 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 baseline (week -1) and week 56 was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Time Frame	Week -1, week 56

Outcome Measure Data

Analysis Population Description

SAS included all randomised participants exposed to at least one dose of trial drug. "Number analyzed"=participants with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	195	197
Abdomen (week -1) Normal	165 83.3%	169 85.4%
Abdomen (week -1) Abnormal, NCS	25 12.6%	25 12.6%
Abdomen (week -1) Abnormal CS	5 2.5%	3 1.5%
Abdomen (week 56) Normal	167 84.3%	160 80.8%
Abdomen (week 56) Abnormal, NCS	15 7.6%	24 12.1%
Abdomen (week 56) Abnormal, CS	3 1.5%	3 1.5%
Gastrointestinal System (week -1) Normal	185 93.4%	187 94.4%
Gastrointestinal System (week -1) Abnormal NCS	10 5.1%	10 5.1%
Gastrointestinal System (week -1) Abnormal CS	0 0%	0 0%
Gastrointestinal System (week 56) Normal	175 88.4%	177 89.4%
Gastrointestinal System (week 56) Abnormal NCS	10 5.1%	8 4%
Gastrointestinal System (week 56) Abnormal CS	0 0%	0 0%
Cardiovascular System (week-1) Normal	183 92.4%	182 91.9%
Cardiovascular System (week-1) Abnormal NCS	10 5.1%	15 7.6%
Cardiovascular System (week-1) Abnormal CS	2 1%	0 0%
Cardiovascular System (week 56) Normal	178 89.9%	175 88.4%
Cardiovascular System (week 56) Abnormal NCS	6 3%	12 6.1%
Cardiovascular System (week 56) Abnormal CS	1 0.5%	0 0%
Nervous System (week -1) Normal	158 79.8%	159 80.3%
Nervous System (week -1) Abnormal NCS	26 13.1%	25 12.6%
Nervous System (week -1) Abnormal CS	11 5.6%	13 6.6%
Nervous System (week 56) Normal	150 75.8%	149 75.3%
Nervous System (week 56) Abnormal NCS	22 11.1%	24 12.1%
Nervous System (week 56) Abnormal CS	13 6.6%	14 7.1%
General Appearance (week -1) Normal	150 75.8%	150 75.8%
General Appearance (week -1) Abnormal NCS	39 19.7%	36 18.2%
General Appearance (week -1) Abnormal CS	6 3%	11 5.6%
General Appearance (week 56) Normal	156 78.8%	151 76.3%
General Appearance (week 56) Abnormal NCS	23 11.6%	27 13.6%
General Appearance (week 56) Abnormal CS	6 3%	9 4.5%
Head, eyes, ENTand Neck (week -1) Normal	176 88.9%	182 91.9%
Head, eyes, ENTand Neck (week -1) Abnormal NCS	17 8.6%	13 6.6%
Head, eyes, ENTand Neck (week -1) Abnormal CS	2 1%	2 1%
Head, eyes, ENTand Neck (week 56) Normal	168 84.8%	173 87.4%
Head, eyes, ENTand Neck (week 56) Abnormal NCS	15 7.6%	12 6.1%
Head, eyes, ENTand Neck (week 56) Abnormal CS	2 1%	2 1%
Lymph Node Palpation (week -1) Normal	195 98.5%	197 99.5%
Lymph Node Palpation (week -1) Abnormal NCS	0 0%	0 0%
Lymph Node Palpation (week -1) Abnormal CS	0 0%	0 0%
Lymph Node Palpation (week 56) Normal	185 93.4%	186 93.9%
Lymph Node Palpation (week 56) Abnormal NCS	0 0%	0 0%
Lymph Node Palpation (week 56) Abnormal CS	0 0%	0 0%
Musculoskeletal System (week -1) Normal	180 90.9%	180 90.9%
Musculoskeletal System (week -1) Abnormal NCS	13 6.6%	16 8.1%
Musculoskeletal System (week -1) Abnormal CS	2 1%	1 0.5%
Musculoskeletal System (week 56) Normal	171 86.4%	171 86.4%
Musculoskeletal System (week 56) Abnormal NCS	13 6.6%	14 7.1%
Musculoskeletal System (week 56) Abnormal CS	1 0.5%	2 1%
Respiratory System (week -1) Normal	192 97%	192 97%
Respiratory System (week -1) Abnormal NCS	3 1.5%	3 1.5%
Respiratory System (week -1) Abnormal CS	0 0%	2 1%
Respiratory System (week 56) Normal	183 92.4%	185 93.4%
Respiratory System (week 56) Abnormal NCS	2 1%	0 0%
Respiratory System (week 56) Abnormal CS	0 0%	2 1%
Skin (week -1) Normal	155 78.3%	156 78.8%
Skin (week -1) Abnormal NCS	36 18.2%	33 16.7%
Skin (week -1) Abnormal CS	4 2%	8 4%
Skin (week 56) Normal	150 75.8%	149 75.3%
Skin (week 56) Abnormal NCS	28 14.1%	29 14.6%
Skin (week 56) Abnormal CS	7 3.5%	9 4.5%
Thyroid Gland (week -1) Normal	183 92.4%	187 94.4%
Thyroid Gland (week -1) Abnormal NCS	10 5.1%	7 3.5%
Thyroid Gland (week -1) Abnormal CS	2 1%	3 1.5%
Thyroid Gland (week 56) Normal	180 90.9%	178 89.9%
Thyroid Gland (week 56) Abnormal NCS	5 2.5%	6 3%
Thyroid Gland (week 56) Abnormal CS	0 0%	3 1.5%

32. Secondary Outcome

Title	Change in Resting Pulse
Description	Change from baseline (week -1) to week 56 in resting pulse was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Time Frame	Week -1, week 56

Outcome Measure Data

Analysis Population Description

SAS included all randomised participants exposed to at least one dose of trial drug. "Number analyzed" = participants with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	195	197
Mean (Standard Deviation) [Beats/minute]	2 (9)	-0 (9)

33. Secondary Outcome

Title	Change in Electrocardiogram (ECG)
Description	The ECGs were interpreted by the investigator at baseline (week -1) and week 56 and categorised as normal, abnormal NCS or abnormal CS. Number of participants in each ECG category at baseline and week 56 were presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Time Frame	Week -1, week 56

Outcome Measure Data

Analysis Population Description

SAS included all randomised participants exposed to at least one dose of trial drug. "Number analyzed"=participants with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	195	197
Normal (week -1)	113 57.1%	133 67.2%
Abnormal NCS (week -1)	78 39.4%	60 30.3%
Abnormal CS (week -1)	4 2%	4 2%
Normal (week 56)	118 59.6%	126 63.6%
Abnormal NCS (week 56)	62 31.3%	57 28.8%
Abnormal CS (week 56)	5 2.5%	3 1.5%

34. Secondary Outcome

Title	Change in Laboratory Measurements (Haematology) - Haemoglobin
Description	Change from baseline (week 0) to week 56 in haemoglobin was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description

SAS included all randomised participants exposed to at least one dose of trial drug. "Number analyzed"=participants with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	195	197
Mean (Standard Deviation) [mmol/L]	-0.1 (0.5)	-0.1 (0.6)

35. Secondary Outcome

Title	Change in Laboratory Measurements (Haematology) - Haematocrit
Description	Change from baseline (week 0) to week 56 in Haematocrit was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description

SAS included all randomised participants exposed to at least one dose of trial drug. "Number analyzed"=participants with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	195	197
Mean (Standard Deviation) [Percentage of red blood cells]	-0.4 (2.8)	-0.2 (3.0)

36. Secondary Outcome

Title	Change in Laboratory Measurements (Haematology) - Erythrocytes
Description	Change from baseline (week 0) to week 56 in erythrocytes was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description

SAS included all randomised participants exposed to at least one dose of trial drug. "Number analyzed"=participants with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	195	197
Mean (Standard Deviation) [10^12 cells per liter (10^12 cells/L)]	-0.07 (0.27)	-0.04 (0.28)

37. Secondary Outcome

Title	Change in Laboratory Measurements (Haematology) - Thrombocytes, Leukocytes
Description	Change from baseline (week 0) to week 56 in thrombocytes and leukocytes was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description

SAS included all randomised participants exposed to at least one dose of trial drug. "Number analyzed"=participants with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	195	197
Thrombocytes	7 (45)	7 (46)
Leukocytes	-0.22 (1.41)	-0.24 (1.28)

38. Secondary Outcome

Title	Change in Laboratory Parameters (Biochemistry) - Albumin
Description	Change from baseline (week 0) to week 56 in albumin was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description

SAS included all randomised participants exposed to at least one dose of trial drug. "Number analyzed"=participants with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	195	197
Mean (Standard Deviation) [Grams per deciliter (g/dL)]	-0.1 (0.2)	-0.1 (0.2)

39. Secondary Outcome

Title	Change in Laboratory Parameters (Biochemistry) - Alkaline Phosphatase, Alanine Aminotransferase, Amylase, Aspartate Aminotransferase and Lipase
Description	Change from baseline (week 0) to week 56 in alkaline phosphatase, alanine aminotransferase, amylase, aspartate aminotransferase and lipase was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description

SAS included all randomised participants exposed to at least one dose of trial drug. "Number analyzed"=participants with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	195	197
Alkaline Phosphatase	-1 (16)	-0 (15)
Alanine Aminotransferase	-5 (15)	-6 (18)
Amylase	13 (73)	-1 (22)
Aspartate aminotransferase	-3 (11)	-3 (14)
Lipase	30 (143)	-8 (47)

40. Secondary Outcome

Title	Change in Laboratory Parameters (Biochemistry) - Bicarbonate, Total Calcium, Potassium, Sodium and Urea
Description	Change from baseline (week 0) to week 56 in bicarbonate, total calcium, potassium, sodium and urea was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description

SAS included all randomised participants exposed to at least one dose of trial drug. "Number analyzed"=participants with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	195	197
Bicarbonate serum	0 (2)	-0 (2)
Total Calcium	-0.00 (0.11)	-0.02 (0.14)
Potassium	-0.0 (0.5)	-0.0 (0.5)
Sodium	-1 (2)	-0 (3)
Urea	0.1 (1.5)	0.1 (1.4)

41. Secondary Outcome

Title	Change in Laboratory Parameters (Biochemistry) - Total Bilirubin and Creatinine
Description	Change from baseline (week 0) to week 56 in total bilirubin and creatinine was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description

SAS included all randomised participants exposed to at least one dose of trial drug. "Number analyzed"=participants with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	195	197
Total Bilirubin	1.0 (3.9)	0.6 (3.6)
Creatinine	-0.1 (8.7)	-0.2 (8.4)

42. Secondary Outcome

Title	Change in Laboratory Parameters (Biochemistry) - High Sensitive C-reactive Protein
Description	Change from baseline (week 0) to week 56 in high sensitive C-reactive protein was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description

SAS included all randomised participants exposed to at least one dose of trial drug. "Number analyzed"=participants with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	195	197
Mean (Standard Deviation) [Milligrams per liter (mg/L)]	-1.40 (8.02)	-1.29 (10.07)

43. Secondary Outcome

Title	Change in Laboratory Parameters (Biochemistry) - eGFR
Description	Change from baseline (week 0) to week 56 in estimated GFR serum using Modification of Diet in Renal Disease (MDRD) formula was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description

SAS included all randomised participants exposed to at least one dose of trial drug. "Number analyzed"=participants with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	195	197
Mean (Standard Deviation) [Milliliters per minute per 1.73m^2]	0 (13)	1 (13)

44. Secondary Outcome

Title	Change in Laboratory Parameters (Biochemistry) - Uric Acid
Description	Change from baseline (week 0) to week 56 in uric acid was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description

SAS included all randomised participants exposed to at least one dose of trial drug. "Number analyzed"=participants with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	195	197
Mean (Standard Deviation) [mg/dL]	-0.2 (1.0)	-0.0 (0.9)

45. Secondary Outcome

Title	Change in Laboratory Parameters (Biochemistry) - Calcitonin
Description	Change from baseline (week 0) to week 56 in calcitonin was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description

SAS included all randomised participants exposed to at least one dose of trial drug. "Number analyzed"=participants with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	195	197
Mean (Standard Deviation) [Nanograms per liter (ng/L)]	0.0 (1.5)	0.0 (1.4)

46. Secondary Outcome

Title	Change in Laboratory Parameters (Biochemistry) - Thyroid Stimulating Hormone
Description	Change from baseline (week 0) to week 56 in thyroid stimulating hormone was presented based on in-trial data. In-trial observation period: the uninterrupted time interval from the date of randomisation until and including the date of the follow-up visit or date of last contact.
Time Frame	Week 0, week 56

Outcome Measure Data

Analysis Population Description

SAS included all randomised participants exposed to at least one dose of trial drug. "Number analyzed"=participants with available data.

Arm/Group Title	Liraglutide 3.0 mg	Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.	Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
Measure Participants	195	197
Mean (Standard Deviation) [Milli-international units per liter]	-0.0842 (1.2233)	0.1002 (0.9493)

Adverse Events

Time Frame	From the date of first dose of trial product (week 0) to end of treatment (week 56) + post treatment follow-up of 30 days.
Adverse Event Reporting Description	Evaluation of safety was based on SAS which comprised of all randomised participants who received at least one dose of trial product. AEs with onset during the on-treatment observation period (the period when participants were exposed to trial product) were considered treatment-emergent.
Arm/Group Title	Liraglutide 3.0 mg		Placebo
Arm/Group Description	Participants received liraglutide once daily by subcutaneous injection irrespective of the timing of meals. Participants received 0.6 mg liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the maintenance dose of 3.0 mg was reached after 4 weeks. The treatment period was 56 weeks.		Participants received matching placebo once daily by subcutaneous injection irrespective of the timing of meals. Dose escalation for placebo matched that of liraglutide. The treatment period was 56 weeks.
All Cause Mortality
	Liraglutide 3.0 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/195 (0%)		0/197 (0%)
Serious Adverse Events
	Liraglutide 3.0 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/195 (8.2%)		19/197 (9.6%)
Cardiac disorders
Angina pectoris	0/195 (0%)	0	1/197 (0.5%)	1
Atrial fibrillation	0/195 (0%)	0	1/197 (0.5%)	1
Atrial flutter	0/195 (0%)	0	2/197 (1%)	2
Cardiac failure congestive	0/195 (0%)	0	1/197 (0.5%)	1
Coronary artery disease	1/195 (0.5%)	1	0/197 (0%)	0
Gastrointestinal disorders
Diverticulum	1/195 (0.5%)	1	0/197 (0%)	0
Duodenal ulcer haemorrhage	0/195 (0%)	0	1/197 (0.5%)	1
Gastrointestinal haemorrhage	0/195 (0%)	0	1/197 (0.5%)	1
Pancreatitis	0/195 (0%)	0	1/197 (0.5%)	1
Pancreatitis acute	0/195 (0%)	0	1/197 (0.5%)	1
Peptic ulcer	0/195 (0%)	0	1/197 (0.5%)	1
General disorders
Non-cardiac chest pain	0/195 (0%)	0	1/197 (0.5%)	1
Infections and infestations
Cellulitis	0/195 (0%)	0	1/197 (0.5%)	1
Diverticulitis	1/195 (0.5%)	1	0/197 (0%)	0
Escherichia bacteraemia	0/195 (0%)	0	1/197 (0.5%)	1
Pneumonia	1/195 (0.5%)	1	0/197 (0%)	0
Urinary tract infection	0/195 (0%)	0	1/197 (0.5%)	1
Wound infection	0/195 (0%)	0	1/197 (0.5%)	1
Injury, poisoning and procedural complications
Facial bones fracture	1/195 (0.5%)	1	0/197 (0%)	0
Fall	0/195 (0%)	0	1/197 (0.5%)	1
Hand fracture	0/195 (0%)	0	1/197 (0.5%)	1
Meniscus injury	0/195 (0%)	0	1/197 (0.5%)	1
Metaphyseal corner fracture	1/195 (0.5%)	1	0/197 (0%)	0
Postpericardiotomy syndrome	1/195 (0.5%)	1	0/197 (0%)	0
Subdural haematoma	1/195 (0.5%)	1	0/197 (0%)	0
Urinary retention postoperative	0/195 (0%)	0	1/197 (0.5%)	1
Investigations
Amylase increased	1/195 (0.5%)	1	0/197 (0%)	0
Lipase increased	1/195 (0.5%)	1	0/197 (0%)	0
Metabolism and nutrition disorders
Hypomagnesaemia	0/195 (0%)	0	1/197 (0.5%)	1
Musculoskeletal and connective tissue disorders
Intervertebral disc disorder	1/195 (0.5%)	1	0/197 (0%)	0
Osteoarthritis	2/195 (1%)	2	0/197 (0%)	0
Spinal pain	1/195 (0.5%)	1	0/197 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma pancreas	1/195 (0.5%)	1	0/197 (0%)	0
Invasive lobular breast carcinoma	0/195 (0%)	0	1/197 (0.5%)	1
Malignant melanoma	0/195 (0%)	0	1/197 (0.5%)	1
Renal cell carcinoma	1/195 (0.5%)	1	0/197 (0%)	0
Thyroid adenoma	1/195 (0.5%)	1	0/197 (0%)	0
Nervous system disorders
Haemorrhage intracranial	0/195 (0%)	0	1/197 (0.5%)	1
Relapsing-remitting multiple sclerosis	1/195 (0.5%)	1	0/197 (0%)	0
Renal and urinary disorders
Ureterolithiasis	0/195 (0%)	0	1/197 (0.5%)	1
Urinary incontinence	1/195 (0.5%)	1	0/197 (0%)	0
Reproductive system and breast disorders
Endometrial hyperplasia	1/195 (0.5%)	1	0/197 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pleural effusion	1/195 (0.5%)	1	0/197 (0%)	0
Pulmonary embolism	0/195 (0%)	0	1/197 (0.5%)	1
Surgical and medical procedures
Lipoma excision	1/195 (0.5%)	1	0/197 (0%)	0
Vascular disorders
Peripheral vascular disorder	1/195 (0.5%)	1	0/197 (0%)	0
Other (Not Including Serious) Adverse Events
	Liraglutide 3.0 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	162/195 (83.1%)		141/197 (71.6%)
Gastrointestinal disorders
Abdominal discomfort	11/195 (5.6%)	17	8/197 (4.1%)	11
Abdominal pain upper	12/195 (6.2%)	17	8/197 (4.1%)	9
Constipation	28/195 (14.4%)	36	17/197 (8.6%)	21
Diarrhoea	45/195 (23.1%)	77	30/197 (15.2%)	54
Dyspepsia	12/195 (6.2%)	13	5/197 (2.5%)	5
Gastrooesophageal reflux disease	10/195 (5.1%)	12	2/197 (1%)	2
Nausea	58/195 (29.7%)	105	23/197 (11.7%)	27
Vomiting	32/195 (16.4%)	53	12/197 (6.1%)	13
General disorders
Fatigue	14/195 (7.2%)	18	10/197 (5.1%)	11
Infections and infestations
Gastroenteritis	15/195 (7.7%)	15	5/197 (2.5%)	5
Influenza	12/195 (6.2%)	14	22/197 (11.2%)	26
Nasopharyngitis	42/195 (21.5%)	48	36/197 (18.3%)	49
Sinusitis	9/195 (4.6%)	11	10/197 (5.1%)	11
Upper respiratory tract infection	24/195 (12.3%)	32	29/197 (14.7%)	37
Urinary tract infection	7/195 (3.6%)	12	19/197 (9.6%)	22
Metabolism and nutrition disorders
Decreased appetite	19/195 (9.7%)	24	5/197 (2.5%)	5
Musculoskeletal and connective tissue disorders
Arthralgia	12/195 (6.2%)	14	24/197 (12.2%)	37
Back pain	13/195 (6.7%)	13	12/197 (6.1%)	17
Osteoarthritis	6/195 (3.1%)	9	12/197 (6.1%)	13
Pain in extremity	16/195 (8.2%)	17	19/197 (9.6%)	21
Nervous system disorders
Dizziness	13/195 (6.7%)	18	7/197 (3.6%)	7
Headache	29/195 (14.9%)	36	29/197 (14.7%)	47
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	7/195 (3.6%)	7	10/197 (5.1%)	12
Vascular disorders
Hypertension	4/195 (2.1%)	4	12/197 (6.1%)	14

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.