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Efficacy and Safety of Liraglutide in Combination With Metformin Compared to Metformin Alone, in Children and Adolescents With Type 2 Diabetes (Ellipse™)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01541215
Recruitment Status : Completed
First Posted : February 29, 2012
Results First Posted : December 11, 2018
Last Update Posted : October 1, 2020
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Diabetes
Diabetes Mellitus, Type 2
Interventions Drug: liraglutide
Drug: placebo
Drug: metformin
Enrollment 135
Recruitment Details The trial was conducted at 84 sites in 25 countries.
Pre-assignment Details Eligible subjects entered an 11- to 12-week run-in period where they were to undergo a 3-4 week titration of metformin to a maximum tolerated dose of metformin (≥1000 mg and ≤2000 mg per day) followed by an 8-week maintenance period.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52). After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Period Title: Treatment Period (52 Weeks)
Started 66 69
Exposed 66 68
Completed 56 53
Not Completed 10 16
Reason Not Completed
Withdrawal criteria             6             8
Non-compliance             4             4
Adverse Event             0             1
Unclassified             0             3
Period Title: Follow up 1 (Weeks 53-104)
Started 52 [1] 0 [2]
Completed 50 0
Not Completed 2 0
Reason Not Completed
Lost to Follow-up             1             0
Withdrawal by Subject             1             0
[1]
Subjects who provided safety follow up data were included.
[2]
Follow up was not planned for the subjects who received placebo.
Arm/Group Title Liraglutide 1.8 mg Placebo Total
Hide Arm/Group Description After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52). After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period. Total of all reporting groups
Overall Number of Baseline Participants 66 68 134
Hide Baseline Analysis Population Description
Full analysis set (FAS) - included all randomised subjects receiving at least one dose of liraglutide/placebo
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 66 participants 68 participants 134 participants
14.57  (1.73) 14.57  (1.73) 14.57  (1.72)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 66 participants 68 participants 134 participants
Female
41
  62.1%
42
  61.8%
83
  61.9%
Male
25
  37.9%
26
  38.2%
51
  38.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 66 participants 68 participants 134 participants
Hispanic or Latino
16
  24.2%
23
  33.8%
39
  29.1%
Not Hispanic or Latino
50
  75.8%
45
  66.2%
95
  70.9%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 66 participants 68 participants 134 participants
American Indian or Alaska Native
2
   3.0%
1
   1.5%
3
   2.2%
Asian
10
  15.2%
8
  11.8%
18
  13.4%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
9
  13.6%
7
  10.3%
16
  11.9%
White
42
  63.6%
45
  66.2%
87
  64.9%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
3
   4.5%
7
  10.3%
10
   7.5%
Glycosylated hemoglobin (HbA1c)  
Mean (Standard Deviation)
Unit of measure:  Percentage of HbA1c
Number Analyzed 66 participants 68 participants 134 participants
7.87  (1.35) 7.69  (1.34) 7.78  (1.34)
1.Primary Outcome
Title Change in HbA1c (Glycosylated Haemoglobin)
Hide Description Change in HbA1c from baseline to week 26. All available data were used for the primary analysis, including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 26
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 66 68
Least Squares Mean (Standard Error)
Unit of Measure: Percentage of HbA1c
-0.643  (0.215) 0.415  (0.216)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Liraglutide 1.8 mg, Placebo
Comments Analysis using a pattern mixture model of observed data with missing observations imputed from the placebo arm based on multiple (x10.000) imputations. The data for week 26 were then analysed with an ANCOVA model containing treatment, sex and age group as fixed effects and baseline value as covariate. The estimated treatment differences and confidence intervals were combined using Rubins formula.
Type of Statistical Test Superiority
Comments

Stepwise hierarchical testing procedure was applied for confirmatory endpoints:

Step 1: Primary analysis: change from baseline to week 26 in HbA1c

Superiority of liraglutide over placebo was to be concluded if the 95% confidence interval for the treatment difference for change from baseline in HbA1c (%) after 26 weeks of randomised treatment was entirely below 0%, implying that the two sided p-value was less than 5%.

Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Pattern Mixture Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -1.058
Confidence Interval (2-Sided) 95%
-1.653 to -0.464
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.304
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Fasting Plasma Glucose (FPG)
Hide Description Change in FPG from baseline to week 26. All available data were used for the analysis, including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 26
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 66 68
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
-1.076  (0.436) 0.801  (0.449)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Liraglutide 1.8 mg, Placebo
Comments Analysis using a pattern mixture model of observed data with missing observations imputed from the placebo arm based on multiple (x10.000) imputations. The data for weeks 26 were then analysed with an ANCOVA model containing treatment, sex and age group as fixed effects and baseline value as covariate. The estimated treatment differences and confidence intervals were combined using Rubins formula.
Type of Statistical Test Superiority
Comments

Stepwise hierarchical testing procedure was applied for confirmatory endpoints:

Step 2: Change from baseline in FPG after 26 weeks of treatment

Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Pattern Mixture Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -1.878
Confidence Interval (2-Sided) 95%
-3.093 to -0.662
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.620
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Number of Subjects Having HbA1c Below 7.0%
Hide Description Percentage of subjects having HbA1c <7.0%. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 26
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 66 68
Measure Type: Number
Unit of Measure: Percentage of subjects
63.7 36.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Liraglutide 1.8 mg, Placebo
Comments Missing data was imputed using pattern mixture model. For each imputed data set the binary response was analysed in a logistic regression model using a logit link with treatment and stratification group (gender*age group) as fixed factors and baseline HbA1c as covariate.The estimated treatment effects and confidence intervals were combined using Rubin´s formula.
Type of Statistical Test Superiority
Comments

Stepwise hierarchical testing procedure was applied for confirmatory endpoints:

Step 3: HbA1c < 7.0% after 26 weeks of treatment

Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method logistic regression model
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment odds ratio
Estimated Value 5.353
Confidence Interval (2-Sided) 95%
2.105 to 13.615
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in Body Mass Index (BMI) Standard Deviation Score (SDS)
Hide Description Change in BMI SDS from baseline to week 26. BMI SDS was calculated using the following formula: Z=[(value /M)^L - 1] / S*L; where L, M and S are median (M), skewness (L) and variation coefficient (S) of children/adolescents' BMI provided for each sex and age. For each subject, a standard deviation score Z (SDS) was calculated based on age and sex referring to the values L, M and S. The method is described in the world health organisation (WHO) Multicentre Growth Reference, which also contains the values for L, M and S by age and sex. For Z (SDS) scores below -3 and above 3, the score was adjusted as described in the WHO instruction. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 26
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 66 68
Least Squares Mean (Standard Error)
Unit of Measure: SDS score
-0.254  (0.039) -0.208  (0.039)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Liraglutide 1.8 mg, Placebo
Comments Analysis using a pattern mixture model of observed data with missing observations imputed from the placebo arm based on multiple (x10.000) imputations. The data for weeks 26 were then analysed with an ANCOVA model containing treatment, sex and age group as fixed effects and baseline value as covariate. The estimated treatment differences and confidence intervals were combined using Rubins formula.
Type of Statistical Test Superiority
Comments

Stepwise hierarchical testing procedure was applied for confirmatory endpoints:

Step 4: Change from baseline in BMI SDS after 26 weeks of treatment

Statistical Test of Hypothesis P-Value 0.392
Comments [Not Specified]
Method Pattern Mixture Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatment difference
Estimated Value -0.047
Confidence Interval (2-Sided) 95%
-0.153 to 0.060
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.055
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Number of Subjects Having HbA1c Below 7.0%
Hide Description Number of subjects achieving HbA1c <7.0% after 52 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 56 52
Measure Type: Count of Participants
Unit of Measure: Participants
Yes
27
  48.2%
16
  30.8%
No
29
  51.8%
36
  69.2%
6.Secondary Outcome
Title Number of Subjects Having HbA1c Maximum 6.5%
Hide Description Number of subjects achieving HbA1c <=6.5% after 26 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 26
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 59 58
Measure Type: Count of Participants
Unit of Measure: Participants
Yes
28
  47.5%
19
  32.8%
No
31
  52.5%
39
  67.2%
7.Secondary Outcome
Title Number of Subjects Having HbA1c Maximum 6.5%
Hide Description Number of subjects achieving HbA1c <=6.5% after 52 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 56 52
Measure Type: Count of Participants
Unit of Measure: Participants
Yes
25
  44.6%
13
  25.0%
No
31
  55.4%
39
  75.0%
8.Secondary Outcome
Title Number of Subjects Having HbA1c Below 7.0% Without Severe or Minor Hypoglycaemic Episodes
Hide Description

Number of subjects achieving HbA1c <7.0% without severe or minor hypoglycaemic episodes after 26 weeks.

Severe hypoglycaemia: An episode requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions.

Minor hypoglycaemia was defined as meeting either of the below criteria:

  1. an episode with symptoms consistent with hypoglycaemia with confirmation by blood glucose <2.8 mmol/L (50 mg/dL) or plasma glucose <3.1 mmol/L (56 mg/dL), and which was handled by the subject him/herself
  2. any asymptomatic blood glucose value <2.8 mmol/L (50 mg/dL) or plasma glucose value <3.1 mmol/L (56 mg/dL) All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 26
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 59 58
Measure Type: Count of Participants
Unit of Measure: Participants
Yes
31
  52.5%
21
  36.2%
No
28
  47.5%
37
  63.8%
9.Secondary Outcome
Title Number of Subjects Having HbA1c Below 7.0% Without Severe or Minor Hypoglycaemic Episodes
Hide Description

Number of subjects achieving HbA1c <7.0% without severe or minor hypoglycaemic episodes after 52 weeks.

Severe hypoglycaemia: An episode requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions.

Minor hypoglycaemia was defined as meeting either of the below criteria:

  1. an episode with symptoms consistent with hypoglycaemia with confirmation by blood glucose <2.8 mmol/L (50 mg/dL) or plasma glucose <3.1 mmol/L (56 mg/dL), and which was handled by the subject him/herself
  2. any asymptomatic blood glucose value <2.8 mmol/L (50 mg/dL) or plasma glucose value <3.1 mmol/L (56 mg/dL) All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 56 52
Measure Type: Count of Participants
Unit of Measure: Participants
Yes
22
  39.3%
16
  30.8%
No
34
  60.7%
36
  69.2%
10.Secondary Outcome
Title Number of Subjects Having HbA1c Below 7.5%
Hide Description Number of subjects achieving HbA1c <7.5% after 26 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 26
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 59 58
Measure Type: Count of Participants
Unit of Measure: Participants
Yes
43
  72.9%
29
  50.0%
No
16
  27.1%
29
  50.0%
11.Secondary Outcome
Title Number of Subjects Having HbA1c Below 7.5%
Hide Description Number of subjects achieving HbA1c <7.5% after 52 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 56 52
Measure Type: Count of Participants
Unit of Measure: Participants
Yes
36
  64.3%
23
  44.2%
No
20
  35.7%
29
  55.8%
12.Secondary Outcome
Title Change in HbA1c
Hide Description Change in HbA1c from baseline to week 52. All available data were used for the analysis, including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 56 52
Mean (Standard Deviation)
Unit of Measure: percentage of HbA1c
-0.732  (1.423) 0.677  (1.523)
13.Secondary Outcome
Title Change in FPG
Hide Description Change in FPG from baseline to week 52. All available data were used for the analysis, including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 56 53
Mean (Standard Deviation)
Unit of Measure: mmol/L
-1.627  (2.717) 0.983  (3.954)
14.Secondary Outcome
Title Change in Mean 7-point Self-measured Plasma Glucose
Hide Description Change in mean 7-point self-measured plasma glucose after 26 weeks. Subjects were instructed to measure their plasma glucose at following timepoints: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner and at bedtime. Mean 7-point SMPG was defined as the area under the profile (calculated using the trapezoidal method) divided by time. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 26
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 39 46
Mean (Standard Deviation)
Unit of Measure: mmol/L
-2.384  (2.638) 0.198  (2.056)
15.Secondary Outcome
Title Change From Baseline in 7-point Self-measured Plasma Glucose
Hide Description Change in mean 7-point self-measured plasma glucose after 52 weeks. Subjects were instructed to measure their plasma glucose at following timepoints: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner and at bedtime. Mean 7-point SMPG was defined as the area under the profile (calculated using the trapezoidal method) divided by time. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 41 39
Mean (Standard Deviation)
Unit of Measure: mmol/L
-2.309  (2.968) -0.748  (1.944)
16.Secondary Outcome
Title Change in Post-prandial Increments (From Before Meal to 90 Min After Breakfast, Lunch, and Dinner)
Hide Description Change in post-prandial increments (from before meal to 90 min after breakfast, lunch, and dinner) after 26 weeks. Post-prandial increment for each meal (breakfast, lunch, and dinner) was derived from the 7-point SMPG profile as the difference between post-prandial plasma glucose values and the plasma glucose values before the meal. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 26
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of analysed=participants with available data for specified timepoints.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 41 46
Mean (Standard Deviation)
Unit of Measure: mmol/L
Breakfast Number Analyzed 37 participants 46 participants
-1.528  (3.168) -0.319  (3.228)
Lunch Number Analyzed 41 participants 43 participants
-0.358  (3.281) -0.658  (3.421)
Dinner Number Analyzed 38 participants 42 participants
0.397  (3.790) -0.226  (2.806)
17.Secondary Outcome
Title Change in Post-prandial Increments (From Before Meal to 90 Min After Breakfast, Lunch, and Dinner)
Hide Description Change in post-prandial increments (from before meal to 90 min after breakfast, lunch, and dinner) after 52 weeks. Post-prandial increment for each meal (breakfast, lunch, and dinner) was derived from the 7-point SMPG profile as the difference between post-prandial plasma glucose values and the plasma glucose values before the meal. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of analysed=participants with available data for specified timepoints.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 42 38
Mean (Standard Deviation)
Unit of Measure: mmol/L
Breakfast Number Analyzed 42 participants 38 participants
-1.802  (3.338) 0.053  (2.124)
Lunch Number Analyzed 42 participants 36 participants
-0.735  (3.809) -1.219  (3.038)
Dinner Number Analyzed 38 participants 36 participants
-0.028  (3.501) -0.195  (2.803)
18.Secondary Outcome
Title Change in Mean Post-prandial Increment Across All Three Meals (Breakfast, Lunch, and Dinner)
Hide Description Change in mean post-prandial increment across all three meals (breakfast, lunch, and dinner) after 26 weeks. Post-prandial increment for each meal (breakfast, lunch, and dinner) was derived from the 7-point SMPG profile as the difference between post-prandial plasma glucose values and the plasma glucose values before the meal. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 26
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 40 46
Mean (Standard Deviation)
Unit of Measure: mmol/L
-0.428  (2.172) -0.362  (1.733)
19.Secondary Outcome
Title Change in Mean Post-prandial Increment Across All Three Meals (Breakfast, Lunch, and Dinner)
Hide Description Change in mean post-prandial increment across all three meals (breakfast, lunch, and dinner) after 52 weeks. Post-prandial increment for each meal (breakfast, lunch, and dinner) was derived from the 7-point SMPG profile as the difference between post-prandial plasma glucose values and the plasma glucose values before the meal. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 41 39
Mean (Standard Deviation)
Unit of Measure: mmol/L
-0.747  (2.245) -0.397  (1.594)
20.Secondary Outcome
Title Change From Baseline in Body Weight
Hide Description Change from baseline in body weight after 26 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 26
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 60 58
Mean (Standard Deviation)
Unit of Measure: kg
-2.48  (5.59) -0.87  (3.84)
21.Secondary Outcome
Title Change From Baseline in Body Weight
Hide Description Change from baseline in body weight after 52 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 56 53
Mean (Standard Deviation)
Unit of Measure: kg
-2.27  (8.05) 1.02  (4.64)
22.Secondary Outcome
Title Change From Baseline in BMI Standard Deviation Score (SDS)
Hide Description Change in BMI SDS from baseline to week 52. BMI SDS was calculated using the following formula: Z=[(value /M)^L - 1] / S*L; where L, M and S are median (M), skewness (L) and variation coefficient (S) of children/adolescents' BMI provided for each sex and age. For each subject, a standard deviation score Z (SDS) was calculated based on age and sex referring to the values L, M and S. The method is described in the WHO Multicentre Growth Reference, which also contains the values for L, M and S by age and sex. For Z (SDS) scores below -3 and above 3, the score was adjusted as described in the WHO instruction. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 56 53
Mean (Standard Deviation)
Unit of Measure: SDS score
-0.361  (0.542) -0.166  (0.330)
23.Secondary Outcome
Title Change in Blood Pressure (Systolic and Diastolic Blood Pressure)
Hide Description Change in blood pressure (systolic and diastolic blood pressure) after 26 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 26
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 60 58
Mean (Standard Deviation)
Unit of Measure: mmHg
Systolic Blood Pressure -1.65  (10.69) 0.03  (10.05)
Diastolic Blood Pressure -1.27  (8.39) 0.97  (7.65)
24.Secondary Outcome
Title Change in Blood Pressure (Systolic and Diastolic Blood Pressure)
Hide Description Change in blood pressure (systolic and diastolic blood pressure) after 52 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 56 53
Mean (Standard Deviation)
Unit of Measure: mmHg
Systolic Blood Pressure -0.77  (11.77) 2.81  (8.48)
Diastolic Blood Pressure 0.46  (10.01) 1.83  (7.26)
25.Secondary Outcome
Title Ratio to Baseline: Fasting Insulin
Hide Description Ratio to baseline (fasting insulin) at week 26. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 26
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 59 57
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ratio
0.9
(76.4%)
1.0
(77.9%)
26.Secondary Outcome
Title Ratio to Baseline: Fasting Insulin
Hide Description Ratio to baseline (fasting insulin) at week 52. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 54 53
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ratio
1.0
(80.6%)
1.1
(142.8%)
27.Secondary Outcome
Title Ratio to Baseline: Fasting Pro-insulin
Hide Description Ratio to baseline (fasting pro-insulin) at week 26. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 26
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 56 55
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ratio
0.62
(110.3%)
0.88
(131.6%)
28.Secondary Outcome
Title Ratio to Baseline: Fasting Pro-insulin
Hide Description Ratio to baseline (fasting pro-insulin) at week 52. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 54 49
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ratio
0.62
(118.0%)
0.79
(121.0%)
29.Secondary Outcome
Title Ratio to Baseline: Pro-insulin/Insulin Ratio
Hide Description Ratio to baseline (Pro-insulin/insulin ratio) after week 26. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 26
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 55 54
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ratio
0.690
(102.4%)
0.923
(197.6%)
30.Secondary Outcome
Title Ratio to Baseline: Pro-insulin/Insulin Ratio
Hide Description Ratio to baseline (Pro-insulin/insulin ratio) after week 52. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 53 49
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ratio
0.689
(106.6%)
0.770
(225.1%)
31.Secondary Outcome
Title Ratio to Baseline: Fasting Glucagon
Hide Description Ratio to baseline (fasting glucagon) at week 26. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 26
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 60 57
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ratio
0.98
(29.3%)
1.03
(32.4%)
32.Secondary Outcome
Title Ratio to Baseline: Fasting Glucagon
Hide Description Ratio to baseline (fasting glucagon) at week 52. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 54 52
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ratio
1.01
(35.0%)
1.05
(32.7%)
33.Secondary Outcome
Title Ratio to Baseline: Fasting C-peptide
Hide Description Ratio to baseline (fasting C-peptide) at week 26. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 26
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 59 58
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ratio
0.93
(39.7%)
0.84
(82.3%)
34.Secondary Outcome
Title Ratio to Baseline: Fasting C-peptide
Hide Description Ratio to baseline (fasting C-peptide) at week 52. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 54 53
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ratio
0.94
(40.8%)
0.83
(56.5%)
35.Secondary Outcome
Title Ratio to Baseline: Homeostasis Model Assessment of Beta-cell Function (HOMA-B)
Hide Description Ratio to baseline (HOMA-B) after 26 weeks. HOMA-B is an index of beta-cell function and was calculated from fasting insulin. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 26
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 56 51
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ratio
1.24
(96.9%)
1.01
(119.0%)
36.Secondary Outcome
Title Ratio to Baseline: HOMA-B
Hide Description Ratio to baseline (HOMA-B) after 52 weeks. HOMA-B is an index of beta-cell function and was calculated from fasting insulin. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 51 49
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ratio
1.48
(105.0%)
0.93
(166.8%)
37.Secondary Outcome
Title Ratio to Baseline: Homeostasis Model Assessment as an Index of Insulin Resistance (HOMA-IR)
Hide Description Ratio to baseline (HOMA-IR) after 26 weeks. HOMA-IR is an index of insulin resistance and was calculated from fasting insulin. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 26
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 58 54
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ratio
0.73
(80.5%)
0.98
(80.8%)
38.Secondary Outcome
Title Ratio to Baseline: HOMA-IR
Hide Description Ratio to baseline (HOMA-IR) after 52 weeks. HOMA-IR is an index of insulin resistance and was calculated from fasting insulin. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 53 52
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ratio
0.82
(86.4%)
1.08
(140.3%)
39.Secondary Outcome
Title Ratio to Baseline: Total Cholesterol
Hide Description Ratio to baseline (total cholesterol) after 26 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 26
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 60 58
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ratio
0.975
(17.7%)
1.008
(13.3%)
40.Secondary Outcome
Title Ratio to Baseline: Total Cholesterol
Hide Description Ratio to baseline (total cholesterol) after 52 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 56 52
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ratio
1.013
(21.0%)
1.026
(13.5%)
41.Secondary Outcome
Title Ratio to Baseline: Low Density Lipoprotein (LDL) Cholesterol
Hide Description Ratio to baseline (LDL cholesterol) after 26 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 26
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 58 57
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ratio
0.998
(24.8%)
0.993
(20.4%)
42.Secondary Outcome
Title Ratio to Baseline: LDL Cholesterol
Hide Description Ratio to baseline (LDL cholesterol) after 52 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 54 48
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ratio
1.042
(46.3%)
1.035
(21.5%)
43.Secondary Outcome
Title Ratio to Baseline: Very Low-density Lipoprotein (VLDL) Cholesterol
Hide Description Ratio to baseline (VLDL cholesterol) after 26 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 26
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 59 58
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ratio
0.890
(51.6%)
1.035
(35.3%)
44.Secondary Outcome
Title Ratio to Baseline: VLDL Cholesterol
Hide Description Ratio to baseline (VLDL cholesterol) after 52 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 56 51
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ratio
0.983
(48.4%)
1.003
(45.5%)
45.Secondary Outcome
Title Ratio to Baseline: High-density Lipoprotein (HDL) Cholesterol
Hide Description Ratio to baseline (HDL cholesterol) after 26 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 26
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 59 58
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ratio
0.997
(18.7%)
0.981
(16.3%)
46.Secondary Outcome
Title Ratio to Baseline: HDL Cholesterol
Hide Description Ratio to baseline (HDL cholesterol) after 52 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 56 51
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ratio
1.028
(16.0%)
1.000
(18.8%)
47.Secondary Outcome
Title Ratio to Baseline: Triglycerides
Hide Description Ratio to baseline (triglycerides) after 26 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 26
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 60 58
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ratio
0.894
(50.6%)
1.038
(36.0%)
48.Secondary Outcome
Title Ratio to Baseline: Triglycerides
Hide Description Ratio to baseline (triglycerides) after 52 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 56 53
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ratio
0.964
(50.5%)
1.036
(48.4%)
49.Secondary Outcome
Title Ratio to Baseline: Free Fatty Acids
Hide Description Ratio to baseline (free fatty acids) after 26 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 26
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 59 58
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ratio
1.023
(67.4%)
0.985
(47.5%)
50.Secondary Outcome
Title Ratio to Baseline: Free Fatty Acids
Hide Description Ratio to baseline (free fatty acids) after 52 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 54 51
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ratio
0.928
(58.2%)
0.868
(54.8%)
51.Secondary Outcome
Title Change From Baseline in Pulse
Hide Description Change from baseline in pulse 26 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 26
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set - included all subjects receiving at least one dose of liraglutide/placebo (134 subjects). Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 60 58
Mean (Standard Deviation)
Unit of Measure: beats/minute
1.40  (10.89) 0.33  (7.69)
52.Secondary Outcome
Title Change From Baseline in Pulse
Hide Description Change from baseline in pulse 52 weeks. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 56 53
Mean (Standard Deviation)
Unit of Measure: beats/minute
-0.05  (10.39) -0.28  (7.88)
53.Secondary Outcome
Title Change From Baseline in Height SDS
Hide Description Change in height SDS from baseline to week 26. Height SDS was calculated using the following formula: Z=[(value /M)^L - 1] / S*L; where L, M and S are median (M), skewness (L) and variation coefficient (S) of children/adolescents' height provided for each sex and age. For each subject, a standard deviation score Z (SDS) was calculated based on age and sex referring to the values L, M and S. The method is described in the WHO Multicentre Growth Reference, which also contains the values for L, M and S by age and sex. For Z (SDS) scores below -3 and above 3, the score was adjusted as described in the WHO instruction. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 26
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 60 58
Mean (Standard Deviation)
Unit of Measure: SDS score
-0.100  (0.133) -0.042  (0.210)
54.Secondary Outcome
Title Change From Baseline in Height SDS
Hide Description Change in height SDS from baseline to week 52. Height SDS was calculated using the following formula: Z=[(value /M)^L - 1] / S*L; where L, M and S are median (M), skewness (L) and variation coefficient (S) of children/adolescents' height provided for each sex and age. For each subject, a standard deviation score Z (SDS) was calculated based on age and sex referring to the values L, M and S. The method is described in the WHO Multicentre Growth Reference, which also contains the values for L, M and S by age and sex. For Z (SDS) scores below -3 and above 3, the score was adjusted as described in the WHO instruction. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 56 53
Mean (Standard Deviation)
Unit of Measure: SDS score
-0.192  (0.223) -0.134  (0.293)
55.Secondary Outcome
Title Change in Bone Age Assessment (X-ray of Left Hand and Wrist)
Hide Description Change in bone age from baseline to week 52. If the baseline (week 0) bone age assessment indicated that all epiphyses were fused, then the assessment was not repeated at week 52.
Time Frame Week 0, week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 31 26
Mean (Standard Deviation)
Unit of Measure: years
1.197  (0.899) 1.088  (0.889)
56.Secondary Outcome
Title Pubertal Assessment/Progression (Tanner Staging)
Hide Description Pubertal development was assessed in 3 areas (breast, penis and pubic hair development) by the Tanner staging in accordance with stages I-V. The Tanner staging assessment was no longer required to be performed once a subject reached the Tanner stage V, as judged by the investigator. Reported results are number of participants at different Tanner stages at week 0, week 26 and week 52.
Time Frame Week 0, week 26, week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set. Number of participants analysed=participants with available data
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 66 68
Measure Type: Count of Participants
Unit of Measure: Participants
Female - Breast development - Week 0 Number Analyzed 41 participants 42 participants
Stage I
1
   2.4%
0
   0.0%
Stage II
2
   4.9%
0
   0.0%
Stage III
4
   9.8%
10
  23.8%
Stage IV
8
  19.5%
9
  21.4%
Stage V
26
  63.4%
23
  54.8%
Female - Breast development - Week 26 Number Analyzed 37 participants 36 participants
Stage I
0
   0.0%
0
   0.0%
Stage II
1
   2.7%
0
   0.0%
Stage III
2
   5.4%
4
  11.1%
Stage IV
5
  13.5%
10
  27.8%
Stage V
29
  78.4%
22
  61.1%
Female - Breast development - Week 52 Number Analyzed 33 participants 33 participants
Stage I
0
   0.0%
0
   0.0%
Stage II
0
   0.0%
0
   0.0%
Stage III
1
   3.0%
2
   6.1%
Stage IV
5
  15.2%
9
  27.3%
Stage V
27
  81.8%
22
  66.7%
Male - Penis Development - Week 0 Number Analyzed 25 participants 26 participants
Stage I
2
   8.0%
0
   0.0%
Stage II
1
   4.0%
3
  11.5%
Stage III
2
   8.0%
6
  23.1%
Stage IV
9
  36.0%
11
  42.3%
Stage V
11
  44.0%
6
  23.1%
Male - Penis Development - Week 26 Number Analyzed 25 participants 23 participants
Stage I
2
   8.0%
0
   0.0%
Stage II
1
   4.0%
1
   4.3%
Stage III
2
   8.0%
4
  17.4%
Stage IV
7
  28.0%
8
  34.8%
Stage V
13
  52.0%
10
  43.5%
Male - Penis Development - Week 52 Number Analyzed 25 participants 21 participants
Stage I
1
   4.0%
0
   0.0%
Stage II
2
   8.0%
0
   0.0%
Stage III
0
   0.0%
2
   9.5%
Stage IV
7
  28.0%
6
  28.6%
Stage V
15
  60.0%
13
  61.9%
Pubic Hair Development - Week 0 Number Analyzed 66 participants 67 participants
Stage I
3
   4.5%
3
   4.5%
Stage II
3
   4.5%
0
   0.0%
Stage III
8
  12.1%
10
  14.9%
Stage IV
14
  21.2%
25
  37.3%
Stage V
38
  57.6%
29
  43.3%
Pubic Hair Development - Week 26 Number Analyzed 62 participants 58 participants
Stage I
3
   4.8%
0
   0.0%
Stage II
0
   0.0%
2
   3.4%
Stage III
5
   8.1%
4
   6.9%
Stage IV
11
  17.7%
18
  31.0%
Stage V
43
  69.4%
34
  58.6%
Pubic Hair Development - Week 52 Number Analyzed 57 participants 53 participants
Stage I
1
   1.8%
0
   0.0%
Stage II
1
   1.8%
0
   0.0%
Stage III
4
   7.0%
2
   3.8%
Stage IV
8
  14.0%
17
  32.1%
Stage V
43
  75.4%
34
  64.2%
57.Secondary Outcome
Title Growth (Height Velocity)
Hide Description Growth (i.e., height velocity) is the change in height per year and is measured in cm/year. The height velocity was calculated as the difference between current height and height at baseline (week 0) divided by the time (in days) between those measurement time points and multiplied by 365 days.
Time Frame Week 0, week 26
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 60 58
Mean (Standard Deviation)
Unit of Measure: cm/year
1.633  (2.016) 2.486  (2.834)
58.Secondary Outcome
Title Growth (Height Velocity)
Hide Description Growth (i.e., height velocity) is the change in height per year and is measured in cm/year. The height velocity was calculated as the difference between current height and height at baseline (week 0) divided by the time (in days) between those measurement time points and multiplied by 365 days.
Time Frame Week 0, week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 56 53
Mean (Standard Deviation)
Unit of Measure: cm/year
1.345  (1.730) 1.817  (2.043)
59.Secondary Outcome
Title Height Velocity SDS
Hide Description Height velocity SDS scores at week 26. Height velocity is change in height per year. The height velocity was calculated as the difference between current height and height at baseline (week 0) divided by time between those measurement time points and multiplied by 365 days. Height velocity SDS was calculated using following formula: Z=[(value /M)^L - 1] / S*L; where L, M and S are median (M), skewness (L) and variation coefficient (S) of children/adolescents' height provided for each sex and age. For each subject, a standard deviation score Z (SDS) was calculated based on age and sex referring to the values L, M and S. The method is described in the WHO Multicentre Growth Reference, which also contains the values for L, M and S by age and sex. For Z (SDS) scores below -3 and above 3, the score was adjusted as described in the WHO instruction. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 26
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 60 58
Mean (Standard Deviation)
Unit of Measure: SDS score
-1.24  (1.695) -0.557  (2.058)
60.Secondary Outcome
Title Height Velocity SDS
Hide Description Height velocity SDS scores at week 52. Height velocity is change in height per year. The height velocity was calculated as the difference between current height and height at baseline (week 0) divided by time between those measurement time points and multiplied by 365 days. Height velocity SDS was calculated using following formula: Z=[(value /M)^L - 1] / S*L; where L, M and S are median (M), skewness (L) and variation coefficient (S) of children/adolescents' height provided for each sex and age. For each subject, a standard deviation score Z (SDS) was calculated based on age and sex referring to the values L, M and S. The method is described in the WHO Multicentre Growth Reference, which also contains the values for L, M and S by age and sex. For Z (SDS) scores below -3 and above 3, the score was adjusted as described in the WHO instruction. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication.
Time Frame Week 0, week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set. Number of participants analysed=participants with available data.
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 52 48
Mean (Standard Deviation)
Unit of Measure: SDS score
-0.887  (1.460) -0.551  (1.711)
61.Secondary Outcome
Title Number of Hypoglycaemic Episodes
Hide Description Total number of hypoglycaemic episodes according to American Diabetes Association (ADA) classification from baseline (week 0) to week 26.
Time Frame 0-26 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 66 68
Measure Type: Number
Unit of Measure: hypoglycaemic episodes
92 43
62.Secondary Outcome
Title Number of Hypoglycaemic Episodes
Hide Description Total number of hypoglycaemic episodes according to American Diabetes Association (ADA) classification from baseline (week 0) to week 52.
Time Frame 0-52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 66 68
Measure Type: Number
Unit of Measure: hypoglycaemic episodes
160 63
63.Secondary Outcome
Title Number of Adverse Events (Week 0-26)
Hide Description Total number of adverse events during 26 weeks.
Time Frame 0-26 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 66 68
Measure Type: Number
Unit of Measure: events
310 230
64.Secondary Outcome
Title Number of Adverse Events (Week 0-52)
Hide Description Total number of adverse events during entire treatment period.
Time Frame 0-52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 66 68
Measure Type: Number
Unit of Measure: events
426 321
65.Secondary Outcome
Title Number of Serious Adverse Events (Week 0-26)
Hide Description Total number of serious adverse events during 26 weeks.
Time Frame 0-26 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 66 68
Measure Type: Number
Unit of Measure: events
7 4
66.Secondary Outcome
Title Number of Serious Adverse Events (Week 0-52)
Hide Description Total number of serious adverse events during entire treatment period.
Time Frame 0-52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title Liraglutide 1.8 mg Placebo
Hide Arm/Group Description:
After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. Subjects treated with liraglutide for more than 3 months were asked to return for follow-up visits one and two years after the end of the open label period (after trial drug cessation at week 52).
After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period.
Overall Number of Participants Analyzed 66 68
Measure Type: Number
Unit of Measure: events
10 5
67.Secondary Outcome
Title Number of Adverse Events (Week 53-104)
Hide Description This outcome is applicable only for the Liraglutide 1.8 mg treatment arm. Number of adverse events reported during follow-up 1 (week 53 to 104).
Time Frame Week 53-104
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set- Subjects who received liraglutide for more than 3 months during the treatment period (week 0-52) and provided safety follow-up data anytime during week 53-104.
Arm/Group Title Liraglutide 1.8 mg: Follow-up 1
Hide Arm/Group Description:
Subjects who received liraglutide for more than 3 months during the treatment period (week 0-52), were followed-up at week 104.
Overall Number of Participants Analyzed 52
Measure Type: Number
Unit of Measure: events
30
68.Secondary Outcome
Title Number of Serious Adverse Events (Week 53-104)
Hide Description This outcome is applicable only for the Liraglutide 1.8 mg treatment arm. Number of serious adverse events reported during follow up 1 (week 53 to 104).
Time Frame Weeks 53-104
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set- Subjects who received liraglutide for more than 3 months during the treatment period (week 0-52) and provided safety follow-up data anytime during week 53-104.
Arm/Group Title Liraglutide 1.8 mg: Follow-up 1
Hide Arm/Group Description:
Subjects who received liraglutide for more than 3 months during the treatment period (week 0-52), were followed-up at week 104.
Overall Number of Participants Analyzed 52
Measure Type: Number
Unit of Measure: events
7
69.Secondary Outcome
Title Growth (Height Velocity)- Week 104
Hide Description Growth (i.e., height velocity) is the change in height per year and is measured in cm/year. The height velocity was calculated as the difference between current height and height at baseline (week 0) divided by the time (in days) between those measurement time points and multiplied by 365 days. This outcome is applicable only for the Liraglutide 1.8 mg treatment arm.
Time Frame Week 0, week 104
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set- Subjects who received liraglutide for more than 3 months during the treatment period (week 0-52) and provided safety follow-up data anytime during week 53-104. Overall number of participants analyzed= subjects with available data.
Arm/Group Title Liraglutide 1.8 mg: Follow-up 1
Hide Arm/Group Description:
Subjects who received liraglutide for more than 3 months during the treatment period (week 0-52), were followed-up at week 104.
Overall Number of Participants Analyzed 50
Mean (Standard Deviation)
Unit of Measure: cm/year
1.149  (1.776)
70.Secondary Outcome
Title Height Velocity SDS- Week 104
Hide Description The height velocity was calculated as the difference between current height and height at baseline (week 0) divided by time between those measurement time points and multiplied by 365 days. Height velocity SDS was calculated using following formula: Z=[(value /M)^L - 1] / S*L; where L, M and S are median (M), skewness (L) and variation coefficient (S) of children/adolescents' height provided for each sex and age. For each subject, a standard deviation score Z (SDS) was calculated based on age and sex referring to the values L, M and S. The method is described in the WHO Multicentre Growth Reference, which also contains the values for L, M and S by age and sex. For Z (SDS) scores below -3 and above 3, the score was adjusted as described in the WHO instruction. This outcome is applicable only for the Liraglutide 1.8 mg treatment arm.
Time Frame Week 0, week 104
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set- Subjects who received liraglutide for more than 3 months during the treatment period (week 0-52) and provided safety follow-up data anytime during week 53-104. Overall number of participants analyzed= subjects with available data.
Arm/Group Title Liraglutide 1.8 mg: Follow-up 1
Hide Arm/Group Description:
Subjects who received liraglutide for more than 3 months during the treatment period (week 0-52), were followed-up at week 104.
Overall Number of Participants Analyzed 41
Mean (Standard Deviation)
Unit of Measure: SDS score
-0.523  (1.466)
71.Secondary Outcome
Title Change From Week 52 in Height SDS- Week 104
Hide Description Change in height SDS from week 52 to week 104. Height SDS was calculated using the following formula: Z=[(value /M)^L - 1] / S*L; where L, M and S are median (M), skewness (L) and variation coefficient (S) of children/adolescents' height provided for each sex and age. For each subject, a standard deviation score Z (SDS) was calculated based on age and sex referring to the values L, M and S. The method is described in the WHO Multicentre Growth Reference, which also contains the values for L, M and S by age and sex. For Z (SDS) scores below -3 and above 3, the score was adjusted as described in the WHO instruction. All available data were used for the analysis including data collected after treatment discontinuation and initiation of rescue medication. This outcome is applicable only for the Liraglutide 1.8 mg treatment arm.
Time Frame Week 52, week 104
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set- Subjects who received liraglutide for more than 3 months during the treatment period (week 0-52) and provided safety follow-up data anytime during week 53-104. Overall number of participants analyzed= subjects with available data.
Arm/Group Title Liraglutide 1.8 mg: Follow-up 1
Hide Arm/Group Description:
Subjects who received liraglutide for more than 3 months during the treatment period (week 0-52), were followed-up at week 104.
Overall Number of Participants Analyzed 49
Mean (Standard Deviation)
Unit of Measure: SDS score
-0.133  (0.338)
72.Secondary Outcome
Title Change in Pubertal Assessment/Progression (Tanner Staging)- Week 104
Hide Description Pubertal development was assessed in 3 areas (breast, penis and pubic hair development) by the Tanner staging in accordance with stages I-V, where stage I represents "pre-adoloscent development" and stage V represents "pubertal development equivalent to that of an adult". The Tanner staging assessment was no longer required to be performed once a subject reached the Tanner stage V, as judged by the investigator. Reported results are number of subjects at different Tanner stages at week 52 and week 104. This outcome is applicable only for the Liraglutide 1.8 mg treatment arm.
Time Frame Week 52, week 104
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set- Subjects who received liraglutide for more than 3 months during the treatment period (week 0-52) and provided safety follow-up data anytime during week 53-104. Number analyzed= subjects with available data.
Arm/Group Title Liraglutide 1.8 mg: Follow-up 1
Hide Arm/Group Description:
Subjects who received liraglutide for more than 3 months during the treatment period (week 0-52), were followed-up at week 104.
Overall Number of Participants Analyzed 52
Measure Type: Count of Participants
Unit of Measure: Participants
Female- Breast development- Week 52 Number Analyzed 27 participants
Stage I
0
   0.0%
Stage II
0
   0.0%
Stage III
1
   3.7%
Stage IV
5
  18.5%
Stage V
21
  77.8%
Female- Breast development- Week 104 Number Analyzed 16 participants
Stage I
0
   0.0%
Stage II
0
   0.0%
Stage III
0
   0.0%
Stage IV
5
  31.3%
Stage V
11
  68.8%
Male- Penis development- Week 52 Number Analyzed 24 participants
Stage I
1
   4.2%
Stage II
2
   8.3%
Stage III
0
   0.0%
Stage IV
7
  29.2%
Stage V
14
  58.3%
Male- Penis development- Week 104 Number Analyzed 14 participants
Stage I
0
   0.0%
Stage II
1
   7.1%
Stage III
0
   0.0%
Stage IV
5
  35.7%
Stage V
8
  57.1%
Female- Pubic hair development- Week 52 Number Analyzed 26 participants
Stage I
0
   0.0%
Stage II
0
   0.0%
Stage III
2
   7.7%
Stage IV
2
   7.7%
Stage V
22
  84.6%
Female- Pubic hair development- Week 104 Number Analyzed 16 participants
Stage I
0
   0.0%
Stage II
0
   0.0%
Stage III
1
   6.3%
Stage IV
2
  12.5%
Stage V
13
  81.3%
Male- Pubic hair development- Week 52 Number Analyzed 24 participants
Stage I
1
   4.2%
Stage II
1
   4.2%
Stage III
2
   8.3%
Stage IV
6
  25.0%
Stage V
14
  58.3%
Male- Pubic hair development- Week 104 Number Analyzed 14 participants
Stage I
0
   0.0%
Stage II
1
   7.1%
Stage III
0
   0.0%
Stage IV
4
  28.6%
Stage V
9
  64.3%
73.Secondary Outcome
Title Change From Week 52 in Bone Age Assessment (X-ray of Left Hand and Wrist)- Week 104
Hide Description Change in bone age from week 52 to week 104. This outcome is applicable only for the Liraglutide 1.8 mg treatment arm.
Time Frame Week 52, week 104
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Hide Analysis Population Description
Safety analysis set- Subjects who received liraglutide for more than 3 months during the treatment period (week 0-52) and provided safety follow-up data anytime during week 53-104. Overall number of participants analyzed= subjects with available data.
Arm/Group Title Liraglutide 1.8 mg: Follow-up 1
Hide Arm/Group Description:
Subjects who received liraglutide for more than 3 months during the treatment period (week 0-52), were followed-up at week 104.
Overall Number of Participants Analyzed 13
Mean (Standard Deviation)
Unit of Measure: Years
1.231  (0.992)
74.Secondary Outcome
Title Number of Adverse Events (Week 53-156)
Hide Description [Not Specified]
Time Frame Weeks 53-156
Outcome Measure Data Not Reported
75.Secondary Outcome
Title Number of Serious Adverse Events (Week 53-156)
Hide Description [Not Specified]
Time Frame Weeks 53-156
Outcome Measure Data Not Reported
76.Secondary Outcome
Title Growth (Height Velocity)- Week 156
Hide Description [Not Specified]
Time Frame Week 0, week 156
Outcome Measure Data Not Reported
77.Secondary Outcome
Title Height Velocity SDS- Week 156
Hide Description [Not Specified]
Time Frame Week 0, week 156
Outcome Measure Data Not Reported
78.Secondary Outcome
Title Change From Week 52 in Height SDS- Week 156
Hide Description [Not Specified]
Time Frame Week 52, week 156
Outcome Measure Data Not Reported
79.Secondary Outcome
Title Pubertal Assessment/Progression (Tanner Staging)- Week 156
Hide Description [Not Specified]
Time Frame Week 52, week 156
Outcome Measure Data Not Reported
80.Secondary Outcome
Title Change in Bone Age Assessment (X-ray of Left Hand and Wrist)- Week 156
Hide Description [Not Specified]
Time Frame Week 52, week 156
Outcome Measure Data Not Reported
Time Frame Week 0 - 104 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration.
Adverse Event Reporting Description Adverse events were reported per different reporting groups for treatment period and follow up period. Results are based on SAS which included subjects: who received at least one dose of liraglutide or placebo for "Liraglutide 1.8 mg- Treatment period" and "Placebo" and who received liraglutide for more than 3 months during treatment period (week 0-52) and provided follow-up data anytime during week 53-104 for "Liraglutide 1.8 mg: Follow-up 1".
 
Arm/Group Title Liraglutide 1.8 mg- Treatment Period Placebo Liraglutide 1.8 mg: Follow-up 1
Hide Arm/Group Description After the run-in period, subjects were randomized to receive liraglutide subcutaneous injections once daily (in combination with metformin with or without basal insulin, on a background of diet and exercise) for 52 weeks (26 weeks double blind treatment period followed by a 26-week open-label extension period). The liraglutide dosing was started at 0.6 mg/day during the first week and escalated in weekly increments of 0.6 mg over the following 2-3 weeks. Dose escalation was based on tolerability, as judged by the investigator and on the average of three fasting plasma glucose (FPG) measurements performed by the subject at home on the 3 consecutive days before the dose escalation visit being >6.1 mmol/L (110 mg/dL). Subjects were treated with doses of 0.6, 1.2 or 1.8 after dose escalation. After the run-in period, subjects were randomized to receive placebo (in combination with metformin with or without basal insulin, on a background of diet and exercise) for a 26 weeks double blind treatment period. The liraglutide placebo was administered once daily subcutaneously in equivalent volume as liraglutide. After 26 weeks, participants discontinued placebo and continued treatment with metformin (with or without basal insulin) during the open-label period. Subjects who received liraglutide for more than 3 months during the treatment period (week 0-52), were followed-up at week 104.
All-Cause Mortality
Liraglutide 1.8 mg- Treatment Period Placebo Liraglutide 1.8 mg: Follow-up 1
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/66 (0.00%)      0/68 (0.00%)      0/52 (0.00%)    
Hide Serious Adverse Events
Liraglutide 1.8 mg- Treatment Period Placebo Liraglutide 1.8 mg: Follow-up 1
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/66 (13.64%)      4/68 (5.88%)      7/52 (13.46%)    
Ear and labyrinth disorders       
Vertigo  1  1/66 (1.52%)  1 0/68 (0.00%)  0 0/52 (0.00%)  0
Gastrointestinal disorders       
Abdominal pain  1  1/66 (1.52%)  1 0/68 (0.00%)  0 0/52 (0.00%)  0
Diarrhoea  1  1/66 (1.52%)  1 0/68 (0.00%)  0 0/52 (0.00%)  0
Constipation  1  0/66 (0.00%)  0 0/68 (0.00%)  0 1/52 (1.92%)  1
Infections and infestations       
Abscess neck  1  1/66 (1.52%)  1 0/68 (0.00%)  0 0/52 (0.00%)  0
Appendicitis perforated  1  0/66 (0.00%)  0 1/68 (1.47%)  1 0/52 (0.00%)  0
Pneumonia  1  0/66 (0.00%)  0 1/68 (1.47%)  1 0/52 (0.00%)  0
Viral infection  1  1/66 (1.52%)  1 0/68 (0.00%)  0 0/52 (0.00%)  0
Subcutaneous abscess  1  0/66 (0.00%)  0 0/68 (0.00%)  0 1/52 (1.92%)  1
Investigations       
Glycosylated haemoglobin increased  1  1/66 (1.52%)  1 1/68 (1.47%)  1 0/52 (0.00%)  0
Metabolism and nutrition disorders       
Diabetes mellitus inadequate control  1  0/66 (0.00%)  0 1/68 (1.47%)  1 0/52 (0.00%)  0
Hyperglycaemia  1  1/66 (1.52%)  1 1/68 (1.47%)  1 2/52 (3.85%)  2
Musculoskeletal and connective tissue disorders       
Scoliosis  1  1/66 (1.52%)  1 0/68 (0.00%)  0 0/52 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Fibroadenoma of breast  1  1/66 (1.52%)  1 0/68 (0.00%)  0 0/52 (0.00%)  0
Nervous system disorders       
Nervous system disorder  1  1/66 (1.52%)  1 0/68 (0.00%)  0 0/52 (0.00%)  0
Psychiatric disorders       
Depressive symptom  1  0/66 (0.00%)  0 0/68 (0.00%)  0 1/52 (1.92%)  1
Surgical and medical procedures       
Fasciotomy  1  0/66 (0.00%)  0 0/68 (0.00%)  0 1/52 (1.92%)  1
Metabolic surgery  1  0/66 (0.00%)  0 0/68 (0.00%)  0 1/52 (1.92%)  1
1
Term from vocabulary, MedDRA 21
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Liraglutide 1.8 mg- Treatment Period Placebo Liraglutide 1.8 mg: Follow-up 1
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   45/66 (68.18%)      49/68 (72.06%)      7/52 (13.46%)    
Gastrointestinal disorders       
Abdominal pain  1  11/66 (16.67%)  22 5/68 (7.35%)  6 1/52 (1.92%)  1
Abdominal pain upper  1  2/66 (3.03%)  3 8/68 (11.76%)  9 0/52 (0.00%)  0
Constipation  1  4/66 (6.06%)  4 1/68 (1.47%)  1 1/52 (1.92%)  1
Diarrhoea  1  15/66 (22.73%)  21 11/68 (16.18%)  13 0/52 (0.00%)  0
Dyspepsia  1  5/66 (7.58%)  6 1/68 (1.47%)  1 1/52 (1.92%)  1
Nausea  1  19/66 (28.79%)  25 9/68 (13.24%)  12 1/52 (1.92%)  1
Vomiting  1  17/66 (25.76%)  46 6/68 (8.82%)  8 2/52 (3.85%)  2
General disorders       
Pyrexia  1  4/66 (6.06%)  5 5/68 (7.35%)  5 0/52 (0.00%)  0
Infections and infestations       
Gastroenteritis  1  7/66 (10.61%)  8 2/68 (2.94%)  2 0/52 (0.00%)  0
Influenza  1  4/66 (6.06%)  6 6/68 (8.82%)  9 0/52 (0.00%)  0
Nasopharyngitis  1  11/66 (16.67%)  16 19/68 (27.94%)  28 2/52 (3.85%)  2
Pharyngitis  1  4/66 (6.06%)  5 4/68 (5.88%)  6 0/52 (0.00%)  0
Upper respiratory tract infection  1  6/66 (9.09%)  10 5/68 (7.35%)  8 0/52 (0.00%)  0
Investigations       
Alanine aminotransferase increased  1  0/66 (0.00%)  0 4/68 (5.88%)  5 0/52 (0.00%)  0
Metabolism and nutrition disorders       
Decreased appetite  1  4/66 (6.06%)  4 3/68 (4.41%)  3 0/52 (0.00%)  0
Hyperglycaemia  1  4/66 (6.06%)  4 4/68 (5.88%)  4 1/52 (1.92%)  1
Nervous system disorders       
Dizziness  1  8/66 (12.12%)  10 2/68 (2.94%)  4 0/52 (0.00%)  0
Headache  1  14/66 (21.21%)  27 13/68 (19.12%)  39 0/52 (0.00%)  0
Reproductive system and breast disorders       
Dysmenorrhoea  1  3/66 (4.55%)  10 6/68 (8.82%)  11 0/52 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Cough  1  4/66 (6.06%)  7 4/68 (5.88%)  5 0/52 (0.00%)  0
Oropharyngeal pain  1  4/66 (6.06%)  6 6/68 (8.82%)  10 0/52 (0.00%)  0
Rhinorrhoea  1  1/66 (1.52%)  2 4/68 (5.88%)  4 0/52 (0.00%)  0
Skin and subcutaneous tissue disorders       
Rash  1  4/66 (6.06%)  5 1/68 (1.47%)  1 0/52 (0.00%)  0
1
Term from vocabulary, MedDRA 21
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
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Name/Title: Clinical Reporting Anchor and Disclosure (1452)
Organization: Novo Nordisk A/S
Phone: (+1) 866-867-7178
EMail: clinicaltrials@novonordisk.com
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Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT01541215    
Other Study ID Numbers: NN2211-3659
2011-002605-29 ( EudraCT Number )
P/288/2010 ( Other Identifier: EMA (PDCO) )
U1111-1121-8743 ( Other Identifier: WHO )
CTRI/2013/10/004082 ( Registry Identifier: Clinical Trials Registry - India (CTRI) )
First Submitted: February 23, 2012
First Posted: February 29, 2012
Results First Submitted: November 15, 2018
Results First Posted: December 11, 2018
Last Update Posted: October 1, 2020