Effect of Liraglutide or Exenatide Added to an Ongoing Treatment on Blood Glucose Control in Subjects With Type 2 Diabetes (LEAD-6)

This study has been completed.
Sponsor:
Information provided by:
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT00518882
First received: August 20, 2007
Last updated: June 19, 2012
Last verified: June 2012
Results First Received: February 23, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Diabetes
Diabetes Mellitus, Type 2
Interventions: Drug: liraglutide
Drug: exenatide

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
A total of 133 centres in 15 countries: Austria (4), Denmark (6), Finland (5), France (5), Germany (14), Ireland (4), Macedonia (1), Norway (4), Poland (9), Romania (3), Slovenia (3), Spain (4), Sweden (2), Switzerland (4) and United States (65).

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Eligible subjects were subjects with type 2 diabetes being treated with oral anti-diabetic (OAD) therapy(ies) for at least 3 months prior to the study. Three subjects were exposed to study drug prior to randomisation, and thus only included in safety analysis set.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Participant Flow for 2 periods

Period 1:   Double-Blind, Week 0-26
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
STARTED     235 [1]   232 [2]
Randomised     233     231  
COMPLETED     202     187  
NOT COMPLETED     33     45  
Adverse Event                 23                 31  
Lack of Efficacy                 1                 0  
Protocol Violation                 4                 3  
Withdrawal criteria                 1                 1  
Lost to follow up                 2                 1  
Subject decision                 1                 1  
Withdrawal of consent                 1                 3  
Loss of trust                 0                 1  
Fear of hypoglycaemia                 0                 1  
Hypoglycaemia                 0                 2  
Mutual consent                 0                 1  
[1] 2 subjects exposed to study drug before randomisation. Subjects only included in safety analysis set
[2] 1 subject exposed to study drug before randomisation. Subject only included in safety analysis set

Period 2:   Open-Label Extension, Week 26-78
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
STARTED     202     187  
COMPLETED     161     138  
NOT COMPLETED     41     49  
Adverse Event                 3                 9  
Lack of Efficacy                 6                 5  
Protocol Violation                 3                 4  
Withdrawel criteria                 1                 2  
Hypoglycaemia                 0                 1  
Lost to follow up                 1                 1  
Consent withdrawn                 2                 1  
Change in treatment                 1                 1  
Creatine increased                 1                 0  
Decreased kidney function                 1                 0  
Exclusion criteria                 2                 0  
Subject decision                 2                 0  
Completed extension 1 (weeks 26-40)                 18                 25  



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Total Total of all reporting groups

Baseline Measures
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide     Total  
Number of Participants  
[units: participants]
  233     231     464  
Age  
[units: years]
Mean ± Standard Deviation
  56.3  ± 9.8     57.1  ± 10.8     56.7  ± 10.3  
Gender  
[units: participants]
     
Female     119     104     223  
Male     114     127     241  
Ethnicity (NIH/OMB)  
[units: participants]
     
Hispanic or Latino     32     25     57  
Not Hispanic or Latino     201     206     407  
Unknown or Not Reported     0     0     0  
Race (NIH/OMB)  
[units: participants]
     
American Indian or Alaska Native     0     1     1  
Asian     0     4     4  
Native Hawaiian or Other Pacific Islander     1     1     2  
Black or African American     13     12     25  
White     216     210     426  
More than one race     0     0     0  
Unknown or Not Reported     3     3     6  
Previous OAD treatment [1]
[units: participants]
     
Metformin/Sulphonylurea Combination     145     147     292  
Sulphonylurea     24     21     45  
Metformin     64     63     127  
BMI [2]
[units: kg/m2]
Mean ± Standard Deviation
  32.9  ± 5.5     32.9  ± 5.7     32.9  ± 5.6  
Duration of diabetes [3]
[units: years]
Mean ± Standard Deviation
  8.5  ± 6.2     7.9  ± 5.9     8.2  ± 6.0  
HbA1c [4]
[units: percentage of total haemoglobin]
Mean ± Standard Deviation
  8.4  ± 1.0     8.2  ± 1.0     8.3  ± 1.0  
Height  
[units: m]
Mean ± Standard Deviation
  1.68  ± 0.10     1.68  ± 0.10     1.68  ± 0.10  
Weight  
[units: kg]
Mean ± Standard Deviation
  93.1  ± 20.1     93.0  ± 19.5     93.1  ± 19.8  
[1] OAD = Oral Anti-diabetic Drug
[2] Body Mass Index
[3] Number of years since diagnosis
[4] Glycosylated Haemoglobin at screening



  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   Change in Glycosylated A1c (HbA1c) at Week 26   [ Time Frame: week 0, week 26 ]

Measure Type Primary
Measure Title Change in Glycosylated A1c (HbA1c) at Week 26
Measure Description Percentage point change in glycosylated A1c (HbA1c) from baseline (week 0) to 26 weeks (end of randomisation)
Time Frame week 0, week 26  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects exposed to study drug.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  227     226  
Change in Glycosylated A1c (HbA1c) at Week 26  
[units: percentage point of total HbA1c]
Least Squares Mean ± Standard Error
  -1.12  ± 0.08     -0.79  ± 0.08  


Statistical Analysis 1 for Change in Glycosylated A1c (HbA1c) at Week 26
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] Yes
Method [3] ANCOVA
P Value [4] <.0001
Estimated treatment difference, LS Mean [5] -0.33
95% Confidence Interval ( -0.47 to -0.18 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

ANCOVA with treatment, country and previous OAD treatment as fixed effects and baseline HbA1c as covariate.

2 hypotheses were tested: H01: µliraglutide ≥ µexenatide + Δ, HA1: µliraglutide < µexenatide + Δ; Δ=0.4%. If non-inferiority was concluded, a test for superiority was established by a 1-sided test of the hypothesis H02: µliraglutide ≥ µexenatide against HA2: µliraglutide < µexenatide. Superiority was concluded if the upper limit of the 2-sided 95% CI for the difference was below 0%.

[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  Non-inferiority concluded if upper confidence interval of test is below 0.4%
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No multiplicity concerns
[5] Other relevant estimation information:
  No text entered.



2.  Secondary:   Change in Glycosylated A1c (HbA1c), Weeks 26-78   [ Time Frame: week 26, week 78 ]

Measure Type Secondary
Measure Title Change in Glycosylated A1c (HbA1c), Weeks 26-78
Measure Description Percentage point change in glycosylated A1c (HbA1c) from Week 26 (end of randomisation) to Week 78 (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group)
Time Frame week 26, week 78  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study drugs.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  198     183  
Change in Glycosylated A1c (HbA1c), Weeks 26-78  
[units: percentage point of total HbA1c]
Mean ± Standard Deviation
  0.25  ± 0.803     -0.00  ± 0.924  


Statistical Analysis 1 for Change in Glycosylated A1c (HbA1c), Weeks 26-78
Groups [1] Liraglutide -> Liraglutide -> Liraglutide
Method [2] Paired t-test
P Value [3] <0.0001
Mean [4] 0.25
Standard Deviation ± 0.803
95% Confidence Interval ( 0.139 to 0.364 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  A paired t test was made within the treatment group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 – µ26 = 0 against HA: µ78 – µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change in Glycosylated A1c (HbA1c), Weeks 26-78
Groups [1] Exenatide -> Liraglutide -> Liraglutide
Method [2] Paired t-test
P Value [3] 0.9872
Mean [4] -0.00
Standard Deviation ± 0.924
95% Confidence Interval ( -1.36 to 0.134 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  A paired t test was made within the treatment group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 – µ26 = 0 against HA: µ78 – µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



3.  Secondary:   Change in Glycosylated A1c (HbA1c) at Week 78   [ Time Frame: week 0, week 78 ]

Measure Type Secondary
Measure Title Change in Glycosylated A1c (HbA1c) at Week 78
Measure Description Percentage point change in glycosylated A1c (HbA1c) from baseline (week 0) to 78 weeks (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group)
Time Frame week 0, week 78  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study drugs.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  198     183  
Change in Glycosylated A1c (HbA1c) at Week 78  
[units: percentage point of total HbA1c]
Mean ± Standard Deviation
  -0.98  ± 1.119     -0.85  ± 1.105  


Statistical Analysis 1 for Change in Glycosylated A1c (HbA1c) at Week 78
Groups [1] Liraglutide -> Liraglutide -> Liraglutide
Method [2] Paired t-test
P Value [3] <0.0001
Mean [4] -0.98
Standard Deviation ± 1.119
95% Confidence Interval ( -1.137 to -0.823 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analysis was made with a paired t test within the treatment group and 95% confidence intervals for the difference between Weeks 0 and 78 were constructed. H0 was µ78 – µ0 = 0 against HA: µ78 – µ0 ≠ 0. A difference between the two means (Weeks 0 and 78) was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change in Glycosylated A1c (HbA1c) at Week 78
Groups [1] Exenatide -> Liraglutide -> Liraglutide
Method [2] Paired t-test
P Value [3] <0.0001
Mean [4] -0.85
Standard Deviation ± 1.105
95% Confidence Interval ( -1.010 to -0.687 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analysis was made with a paired t test within the exenatide→liraglutide group and 95% confidence intervals for the difference between Weeks 0 and 78 were constructed. H0 was µ78 – µ0 = 0 against HA: µ78 – µ0 ≠ 0. A difference between the two means (Weeks 0 and 78) was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



4.  Secondary:   Percentage of Subjects Achieving Treatment Target of Either HbA1c < 7.0% or =< 6.5% at Week 26   [ Time Frame: week 0, week 26 ]

Measure Type Secondary
Measure Title Percentage of Subjects Achieving Treatment Target of Either HbA1c < 7.0% or =< 6.5% at Week 26
Measure Description Percentage of subjects achieving treatment target of HbA1c less than 7.0% or less than or equal to 6.5% at Week 26 (end of randomisation)
Time Frame week 0, week 26  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects exposed to study drug.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  233     231  
Percentage of Subjects Achieving Treatment Target of Either HbA1c < 7.0% or =< 6.5% at Week 26  
[units: percentage (%) of subjects]
   
Treatment target HbA1c < 7%     53     42  
Treatment target HbA1c =< 6.5%     34     20  

No statistical analysis provided for Percentage of Subjects Achieving Treatment Target of Either HbA1c < 7.0% or =< 6.5% at Week 26



5.  Secondary:   Percentage of Subjects Achieving Treatment Target of Either HbA1c < 7.0% or =< 6.5% at Week 78   [ Time Frame: week 0, week 78 ]

Measure Type Secondary
Measure Title Percentage of Subjects Achieving Treatment Target of Either HbA1c < 7.0% or =< 6.5% at Week 78
Measure Description Percentage of subjects achieving treatment target of HbA1c less than 7.0% or less than or equal to 6.5% at Week 78 (end of treatment)
Time Frame week 0, week 78  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study drugs.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  200     186  
Percentage of Subjects Achieving Treatment Target of Either HbA1c < 7.0% or =< 6.5% at Week 78  
[units: percentage (%) of subjects]
   
Treatment target HbA1c < 7%     47     48  
Treatment target HbA1c =< 6.5%     31     35  

No statistical analysis provided for Percentage of Subjects Achieving Treatment Target of Either HbA1c < 7.0% or =< 6.5% at Week 78



6.  Secondary:   Change in Body Weight at Week 26   [ Time Frame: week 0, week 26 ]

Measure Type Secondary
Measure Title Change in Body Weight at Week 26
Measure Description Change in body weight from baseline (week 0) to 26 weeks (end of randomisation)
Time Frame week 0, week 26  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects exposed to study drug.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  231     229  
Change in Body Weight at Week 26  
[units: kg]
Least Squares Mean ± Standard Error
  -3.24  ± 0.33     -2.87  ± 0.33  


Statistical Analysis 1 for Change in Body Weight at Week 26
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.2235
Estimated treatment difference, LS Mean [4] -0.38
95% Confidence Interval ( -0.99 to 0.23 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  ANCOVA model included treatment, country and previous treatment as fixed effects and baseline body weight as covariate. The objective was to demonstrate that treatment with liraglutide was different from treatment with exenatide. Thus the null hypothesis and its alternative were H0: µliraglutide = µexenatide against HA1:µliraglutide ≠ µexenatide where µliraglutide and µexenatide is the mean value of the body weight in the liraglutide arm and exenatide arm, respectively.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  There were no multiplicity concerns.
[4] Other relevant estimation information:
  No text entered.



7.  Secondary:   Change in Body Weight, Weeks 26-78   [ Time Frame: week 26, week 78 ]

Measure Type Secondary
Measure Title Change in Body Weight, Weeks 26-78
Measure Description Change in body weight from Week 26 (end of randomisation) to Week 78 (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group)
Time Frame week 26, week 78  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study drugs.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  199     184  
Change in Body Weight, Weeks 26-78  
[units: kg]
Mean ± Standard Deviation
  -0.4  ± 3.24     -0.7  ± 3.67  


Statistical Analysis 1 for Change in Body Weight, Weeks 26-78
Groups [1] Liraglutide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] 0.0793
Mean [4] -0.4
Standard Deviation ± 3.24
95% Confidence Interval ( -0.86 to 0.05 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 26 and 78 were constructed. H0 was µ78 – µ26=0 against HA: µ78 – µ26 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change in Body Weight, Weeks 26-78
Groups [1] Exenatide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] 0.0075
Mean [4] -0.7
Standard Deviation ± 3.67
95% Confidence Interval ( -1.26 to -0.20 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  A paired t test was made within the group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 – µ26 = 0 against HA: µ78 – µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



8.  Secondary:   Change in Body Weight at Week 78   [ Time Frame: week 0, week 78 ]

Measure Type Secondary
Measure Title Change in Body Weight at Week 78
Measure Description Change in body weight from baseline (Week 0) to 78 weeks (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group)
Time Frame week 0, week 78  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study drugs.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  199     184  
Change in Body Weight at Week 78  
[units: kg]
Mean ± Standard Deviation
  -3.3  ± 4.63     -3.2  ± 4.44  


Statistical Analysis 1 for Change in Body Weight at Week 78
Groups [1] Liraglutide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] <0.0001
Mean [4] -3.3
Standard Deviation ± 4.63
95% Confidence Interval ( -3.90 to -2.61 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78– µ0=0 against HA: µ78 – µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change in Body Weight at Week 78
Groups [1] Exenatide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] <0.0001
Mean [4] -3.2
Standard Deviation ± 4.44
95% Confidence Interval ( -3.85 to -2.55 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78– µ0=0 against HA: µ78 – µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



9.  Secondary:   Change in Fasting Plasma Glucose at Week 26   [ Time Frame: week 0, week 26 ]

Measure Type Secondary
Measure Title Change in Fasting Plasma Glucose at Week 26
Measure Description Change in fasting plasma glucose (FPG) from baseline (week 0) to 26 weeks (end of randomisation)
Time Frame week 0, week 26  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects exposed to study drug.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  225     219  
Change in Fasting Plasma Glucose at Week 26  
[units: mmol/L]
Least Squares Mean ± Standard Error
  -1.61  ± 0.20     -0.60  ± 0.20  


Statistical Analysis 1 for Change in Fasting Plasma Glucose at Week 26
Groups [1] All groups
Method [2] ANCOVA
P Value [3] <0.0001
Estimated treatment difference, LS Mean [4] -1.01
95% Confidence Interval ( -1.37 to -0.65 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  ANCOVA model included treatment, country and previous treatment as fixed effects and baseline fasting plasma glucose as covariate. The objective was to demonstrate that treatment with liraglutide was different from treatment with exenatide. Thus the null hypothesis and its alternative were H0: µliraglutide = µexenatide against HA1:µliraglutide ≠ µexenatide where µliraglutide and µexenatide is the mean value of the fasting plasma glucose in the liraglutide and exenatide arm, respectively.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  There were no multiplicity concerns.
[4] Other relevant estimation information:
  No text entered.



10.  Secondary:   Change in Fasting Plasma Glucose, Weeks 26-78   [ Time Frame: week 26, week 78 ]

Measure Type Secondary
Measure Title Change in Fasting Plasma Glucose, Weeks 26-78
Measure Description Change in fasting plasma glucose from Week 26 (end of randomisation) to Week 78 (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group)
Time Frame week 26, week 78  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study drugs.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  197     182  
Change in Fasting Plasma Glucose, Weeks 26-78  
[units: mmol/L]
Mean ± Standard Deviation
  0.7  ± -1.84     -0.1  ± 2.42  


Statistical Analysis 1 for Change in Fasting Plasma Glucose, Weeks 26-78
Groups [1] Liraglutide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] <0.0001
Mean [4] 0.7
Standard Deviation ± 1.84
95% Confidence Interval ( 0.48 to 1.00 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 26 and 78 were constructed. H0 was µ78– µ26=0 against HA: µ78 – µ26 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change in Fasting Plasma Glucose, Weeks 26-78
Groups [1] Exenatide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] 0.4864
Mean [4] -0.1
Standard Deviation ± 2.42
95% Confidence Interval ( -0.48 to 0.23 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  A paired t test was made within the group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 – µ26 = 0 against HA: µ78 – µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



11.  Secondary:   Change in Fasting Plasma Glucose at Week 78   [ Time Frame: week 0, week 78 ]

Measure Type Secondary
Measure Title Change in Fasting Plasma Glucose at Week 78
Measure Description Change in fasting plasma glucose from baseline (week 0) to 78 weeks (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group)
Time Frame week 0, week 78  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study drugs.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  197     182  
Change in Fasting Plasma Glucose at Week 78  
[units: mmol/L]
Mean ± Standard Deviation
  -1.3  ± 2.50     -0.8  ± 2.76  


Statistical Analysis 1 for Change in Fasting Plasma Glucose at Week 78
Groups [1] Liraglutide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] <0.0001
Mean [4] -1.3
Standard Deviation ± 2.50
95% Confidence Interval ( -1.62 to -0.92 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78 – µ0=0 against HA: µ78 – µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change in Fasting Plasma Glucose at Week 78
Groups [1] Exenatide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] <0.0001
Mean [4] -0.8
Standard Deviation ± 2.76
95% Confidence Interval ( -1.23 to -0.42 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78 – µ0=0 against HA: µ78 – µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



12.  Secondary:   Change in Mean Prandial Increment of Plasma Glucose After Breakfast at Week 26   [ Time Frame: week 0, week 26 ]

Measure Type Secondary
Measure Title Change in Mean Prandial Increment of Plasma Glucose After Breakfast at Week 26
Measure Description Change in mean prandial increment of plasma glucose after breakfast from baseline (week 0) to 26 weeks (end of randomisation). Prandial increments of plasma glucose were calculated as the difference between glucose values measured before and after breakfast.
Time Frame week 0, week 26  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects exposed to study drug.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  207     196  
Change in Mean Prandial Increment of Plasma Glucose After Breakfast at Week 26  
[units: mmol/L]
Least Squares Mean ± Standard Error
  -0.83  ± 0.28     -2.16  ± 0.28  


Statistical Analysis 1 for Change in Mean Prandial Increment of Plasma Glucose After Breakfast at Week 26
Groups [1] All groups
Method [2] ANCOVA
P Value [3] <.0001
Estimated treatment difference, LS Mean [4] 1.33
95% Confidence Interval ( 0.80 to 1.86 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  ANCOVA model included treatment, country and previous treatment as fixed effects and baseline value of the endpoint as covariate. The objective was to demonstrate that treatment with liraglutide was different from treatment with exenatide. Thus the null hypothesis and its alternative were H0: µliraglutide = µexenatide against HA1:µliraglutide ≠ µexenatide where µliraglutide and µexenatide is the mean value of the endpoint in the liraglutide arm and exenatide arm, respectively.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  There were no multiplicity concerns.
[4] Other relevant estimation information:
  No text entered.



13.  Secondary:   Change in Mean Prandial Increment of Plasma Glucose After Lunch at Week 26   [ Time Frame: week 0, week 26 ]

Measure Type Secondary
Measure Title Change in Mean Prandial Increment of Plasma Glucose After Lunch at Week 26
Measure Description Change in mean prandial increment of plasma glucose after lunch from baseline (week 0) to 26 weeks (end of randomisation). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after lunch.
Time Frame week 0, week 26  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects exposed to study drug.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  207     196  
Change in Mean Prandial Increment of Plasma Glucose After Lunch at Week 26  
[units: mmol/L]
Least Squares Mean ± Standard Error
  0.06  ± 0.28     0.06  ± 0.28  


Statistical Analysis 1 for Change in Mean Prandial Increment of Plasma Glucose After Lunch at Week 26
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.9849
Estimated treatment difference, LS Mean [4] 0.01
95% Confidence Interval ( -0.52 to 0.53 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  ANCOVA model included treatment, country and previous treatment as fixed effects and baseline value of the endpoint as covariate. The objective was to demonstrate that treatment with liraglutide was different from treatment with exenatide. Thus the null hypothesis and its alternative were H0: µliraglutide = µexenatide against HA1:µliraglutide ≠ µexenatide where µliraglutide and µexenatide is the mean value of the endpoint in the liraglutide arm and exenatide arm, respectively.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  There were no multiplicity concerns.
[4] Other relevant estimation information:
  No text entered.



14.  Secondary:   Change in Mean Prandial Increment of Plasma Glucose After Dinner at Week 26   [ Time Frame: week 0, week 26 ]

Measure Type Secondary
Measure Title Change in Mean Prandial Increment of Plasma Glucose After Dinner at Week 26
Measure Description Change in mean prandial increment of plasma glucose after dinner from baseline (week 0) to 26 weeks (end of randomisation). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after dinner.
Time Frame week 0, week 26  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects exposed to study drug.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  204     196  
Change in Mean Prandial Increment of Plasma Glucose After Dinner at Week 26  
[units: mmol/L]
Least Squares Mean ± Standard Error
  -1.10  ± 0.31     -2.11  ± 0.31  


Statistical Analysis 1 for Change in Mean Prandial Increment of Plasma Glucose After Dinner at Week 26
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.0005
LS Mean [4] 1.01
95% Confidence Interval ( 0.44 to 1.57 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  ANCOVA model included treatment, country and previous treatment as fixed effects and baseline value of the endpoint as covariate. The objective was to demonstrate that treatment with liraglutide was different from treatment with exenatide. Thus the null hypothesis and its alternative were H0: µliraglutide = µexenatide against HA1:µliraglutide ≠ µexenatide where µliraglutide and µexenatide is the mean value of the endpoint in the liraglutide arm and exenatide arm, respectively.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  There were no multiplicity concerns.
[4] Other relevant estimation information:
  No text entered.



15.  Secondary:   Change in Mean Prandial Increment of Plasma Glucose After Breakfast, Weeks 26-78   [ Time Frame: week 26, week 78 ]

Measure Type Secondary
Measure Title Change in Mean Prandial Increment of Plasma Glucose After Breakfast, Weeks 26-78
Measure Description Change in mean prandial increment of plasma glucose after breakfast from Week 26 (end of randomisation) to Week 78 (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after breakfast.
Time Frame week 26, week 78  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study drugs.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  191     173  
Change in Mean Prandial Increment of Plasma Glucose After Breakfast, Weeks 26-78  
[units: mmol/L]
Mean ± Standard Deviation
  -0.22  ± 2.866     1.15  ± 3.253  


Statistical Analysis 1 for Change in Mean Prandial Increment of Plasma Glucose After Breakfast, Weeks 26-78
Groups [1] Liraglutide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] 0.2972
Mean [4] -0.22
Standard Deviation ± 2.866
95% Confidence Interval ( -0.626 to 0.192 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  A paired t test was made within the group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 – µ26 = 0 against HA: µ78 – µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change in Mean Prandial Increment of Plasma Glucose After Breakfast, Weeks 26-78
Groups [1] Exenatide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] <0.0001
Mean [4] 1.15
Standard Deviation ± 3.253
95% Confidence Interval ( 0.660 to 1.637 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  A paired t test was made within the group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 – µ26 = 0 against HA: µ78 – µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



16.  Secondary:   Change in Mean Prandial Increment of Plasma Glucose After Lunch, Weeks 26-78   [ Time Frame: week 26, week 78 ]

Measure Type Secondary
Measure Title Change in Mean Prandial Increment of Plasma Glucose After Lunch, Weeks 26-78
Measure Description Change in mean prandial increment of plasma glucose after lunch from Week 26 (end of randomisation) to Week 78 (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after a lunch.
Time Frame week 26, week 78  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study drugs.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  191     173  
Change in Mean Prandial Increment of Plasma Glucose After Lunch, Weeks 26-78  
[units: mmol/L]
Mean ± Standard Deviation
  0.05  ± 3.307     -0.09  ± 3.419  


Statistical Analysis 1 for Change in Mean Prandial Increment of Plasma Glucose After Lunch, Weeks 26-78
Groups [1] Liraglutide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] 0.8396
Mean [4] 0.05
Standard Deviation ± 3.307
95% Confidence Interval ( -0.424 to 0.521 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  A paired t test was made within the group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 – µ26 = 0 against HA: µ78 – µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change in Mean Prandial Increment of Plasma Glucose After Lunch, Weeks 26-78
Groups [1] Exenatide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] 0.7278
Mean [4] -0.09
Standard Deviation ± 3.419
95% Confidence Interval ( -0.604 to 0.423 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  A paired t test was made within the group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 – µ26 = 0 against HA: µ78 – µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



17.  Secondary:   Change in Mean Prandial Increment of Plasma Glucose After Dinner, Weeks 26-78   [ Time Frame: week 26, week 78 ]

Measure Type Secondary
Measure Title Change in Mean Prandial Increment of Plasma Glucose After Dinner, Weeks 26-78
Measure Description Change in mean prandial increment of plasma glucose after dinner from Week 26 (end of randomisation) to Week 78 (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after dinner.
Time Frame week 26, week 78  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study drugs.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  190     172  
Change in Mean Prandial Increment of Plasma Glucose After Dinner, Weeks 26-78  
[units: mmol/L]
Mean ± Standard Deviation
  0.22  ± 3.053     1.07  ± 3.775  


Statistical Analysis 1 for Change in Mean Prandial Increment of Plasma Glucose After Dinner, Weeks 26-78
Groups [1] Liraglutide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] 0.3271
Mean [4] 0.22
Standard Deviation ± 3.053
95% Confidence Interval ( -0.219 to 0.654 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  A paired t test was made within the group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 – µ26 = 0 against HA: µ78 – µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change in Mean Prandial Increment of Plasma Glucose After Dinner, Weeks 26-78
Groups [1] Exenatide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] 0.0003
Mean [4] 1.07
Standard Deviation ± 3.775
95% Confidence Interval ( 0.497 to 1.634 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  A paired t test was made within the group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 – µ26 = 0 against HA: µ78 – µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  .
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



18.  Secondary:   Change in Mean Prandial Increment of Plasma Glucose After Breakfast at Week 78   [ Time Frame: week 0, week 78 ]

Measure Type Secondary
Measure Title Change in Mean Prandial Increment of Plasma Glucose After Breakfast at Week 78
Measure Description Change in mean prandial increment of plasma glucose after breakfast from baseline (week 0) to 78 weeks (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after breakfast.
Time Frame week 0, week 78  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study drugs.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  192     167  
Change in Mean Prandial Increment of Plasma Glucose After Breakfast at Week 78  
[units: mmol/L]
Mean ± Standard Deviation
  -1.08  ± 3.662     -0.99  ± 3.467  


Statistical Analysis 1 for Change in Mean Prandial Increment of Plasma Glucose After Breakfast at Week 78
Groups [1] Liraglutide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] <0.0001
Mean [4] -1.08
Standard Deviation ± 3.662
95% Confidence Interval ( -1.605 to -0.562 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78– µ0=0 against HA: µ78 – µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change in Mean Prandial Increment of Plasma Glucose After Breakfast at Week 78
Groups [1] Exenatide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] 0.0003
Mean [4] -0.99
Standard Deviation ± 3.467
95% Confidence Interval ( -1.517 to -0.458 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78– µ0=0 against HA: µ78 – µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



19.  Secondary:   Change in Mean Prandial Increment of Plasma Glucose After Lunch at Week 78   [ Time Frame: week 0, week 78 ]

Measure Type Secondary
Measure Title Change in Mean Prandial Increment of Plasma Glucose After Lunch at Week 78
Measure Description Change in mean prandial increment of plasma glucose after lunch from baseline (week 0) to 78 weeks (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after lunch.
Time Frame week 0, week 78  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study drugs.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  192     168  
Change in Mean Prandial Increment of Plasma Glucose After Lunch at Week 78  
[units: mmol/L]
Mean ± Standard Deviation
  0.26  ± 4.158     -0.37  ± 3.838  


Statistical Analysis 1 for Change in Mean Prandial Increment of Plasma Glucose After Lunch at Week 78
Groups [1] Liraglutide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] 0.3859
Mean [4] 0.26
Standard Deviation ± 4.158
95% Confidence Interval ( -0.331 to 0.853 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78– µ0=0 against HA: µ78 – µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change in Mean Prandial Increment of Plasma Glucose After Lunch at Week 78
Groups [1] Exenatide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] 0.2119
Mean [4] -0.37
Standard Deviation ± 3.838
95% Confidence Interval ( -0.956 to 0.214 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78– µ0=0 against HA: µ78 – µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



20.  Secondary:   Change in Mean Prandial Increment of Plasma Glucose After Dinner at Week 78   [ Time Frame: week 0, week 78 ]

Measure Type Secondary
Measure Title Change in Mean Prandial Increment of Plasma Glucose After Dinner at Week 78
Measure Description Change in mean prandial increment of plasma glucose after dinner from baseline (week 0) to 78 weeks (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after dinner.
Time Frame week 0, week 78  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study drugs.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  190     166  
Change in Mean Prandial Increment of Plasma Glucose After Dinner at Week 78  
[units: mmol/L]
Mean ± Standard Deviation
  -0.35  ± 3.975     -0.95  ± 3.230  


Statistical Analysis 1 for Change in Mean Prandial Increment of Plasma Glucose After Dinner at Week 78
Groups [1] Liraglutide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] 0.2290
Mean [4] -0.35
Standard Deviation ± 3.975
95% Confidence Interval ( -0.917 to 0.2211 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78– µ0=0 against HA: µ78 – µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change in Mean Prandial Increment of Plasma Glucose After Dinner at Week 78
Groups [1] Exenatide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] 0.0002
Mean [4] -0.95
Standard Deviation ± 3.230
95% Confidence Interval ( -1.449 to -0.459 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78– µ0=0 against HA: µ78 – µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



21.  Secondary:   Change in Mean Postprandial Increment of Plasma Glucose After Breakfast at Week 26   [ Time Frame: week 0, week 26 ]

Measure Type Secondary
Measure Title Change in Mean Postprandial Increment of Plasma Glucose After Breakfast at Week 26
Measure Description Change in mean postprandial increment of plasma glucose after breakfast from baseline (week 0) to 26 weeks (end of randomisation). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after breakfast.
Time Frame week 0, week 26  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects exposed to study drug.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  207     197  
Change in Mean Postprandial Increment of Plasma Glucose After Breakfast at Week 26  
[units: mmol/L]
Least Squares Mean ± Standard Error
  -3.20  ± 0.31     -3.93  ± 0.30  


Statistical Analysis 1 for Change in Mean Postprandial Increment of Plasma Glucose After Breakfast at Week 26
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.0124
Estimated treatment difference, LS Mean [4] 0.73
95% Confidence Interval ( 0.16 to 1.31 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  ANCOVA model included treatment, country and previous treatment as fixed effects and baseline value of the endpoint as covariate. The objective was to demonstrate that treatment with liraglutide was different from treatment with exenatide. Thus the null hypothesis and its alternative were H0: µliraglutide = µexenatide against HA1:µliraglutide ≠ µexenatide where µliraglutide and µexenatide is the mean value of the endpoint in the liraglutide arm and exenatide arm, respectively.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  There were no multiplicity concerns.
[4] Other relevant estimation information:
  No text entered.



22.  Secondary:   Change in Mean Postprandial Increment of Plasma Glucose After Lunch at Week 26   [ Time Frame: week 0. week 26 ]

Measure Type Secondary
Measure Title Change in Mean Postprandial Increment of Plasma Glucose After Lunch at Week 26
Measure Description Change in mean postprandial increment of plasma glucose after lunch from baseline (week 0) to 26 weeks (end of randomisation). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after lunch.
Time Frame week 0. week 26  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects exposed to study drug.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  208     196  
Change in Mean Postprandial Increment of Plasma Glucose After Lunch at Week 26  
[units: mmol/L]
Least Squares Mean ± Standard Error
  -2.74  ± 0.28     -2.35  ± 0.28  


Statistical Analysis 1 for Change in Mean Postprandial Increment of Plasma Glucose After Lunch at Week 26
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.1430
Estimated treatment difference, LS Mean [4] -0.39
95% Confidence Interval ( -0.91 to 0.13 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  ANCOVA model included treatment, country and previous treatment as fixed effects and baseline value of the endpoint as covariate. The objective was to demonstrate that treatment with liraglutide was different from treatment with exenatide. Thus the null hypothesis and its alternative were H0: µliraglutide = µexenatide against HA1:µliraglutide ≠ µexenatide where µliraglutide and µexenatide is the mean value of the endpoint in the liraglutide arm and exenatide arm, respectively.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  There were no multiplicity concerns.
[4] Other relevant estimation information:
  No text entered.



23.  Secondary:   Change in Mean Postprandial Increment of Plasma Glucose After Dinner at Week 26   [ Time Frame: week 0, week 26 ]

Measure Type Secondary
Measure Title Change in Mean Postprandial Increment of Plasma Glucose After Dinner at Week 26
Measure Description Change in mean postprandial increment of plasma glucose after dinner from baseline (week 0) to 26 weeks (end of randomisation). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after dinner.
Time Frame week 0, week 26  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects exposed to study drug.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  206     197  
Change in Mean Postprandial Increment of Plasma Glucose After Dinner at Week 26  
[units: mmol/L]
Least Squares Mean ± Standard Error
  -3.05  ± 0.28     -3.59  ± 0.27  


Statistical Analysis 1 for Change in Mean Postprandial Increment of Plasma Glucose After Dinner at Week 26
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.0380
Estimated treatment difference, LS Mean [4] 0.54
95% Confidence Interval ( 0.03 to 1.05 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  ANCOVA model included treatment, country and previous treatment as fixed effects and baseline value of the endpoint as covariate. The objective was to demonstrate that treatment with liraglutide was different from treatment with exenatide. Thus the null hypothesis and its alternative were H0: µliraglutide = µexenatide against HA1:µliraglutide ≠ µexenatide where µliraglutide and µexenatide is the mean value of the endpoint in the liraglutide arm and exenatide arm, respectively.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  There were no multiplicity concerns.
[4] Other relevant estimation information:
  No text entered.



24.  Secondary:   Change in Mean Postprandial Increment of Plasma Glucose After Breakfast, Weeks 26-78   [ Time Frame: week 26, week 78 ]

Measure Type Secondary
Measure Title Change in Mean Postprandial Increment of Plasma Glucose After Breakfast, Weeks 26-78
Measure Description Change in mean postprandial increment of plasma glucose after breakfast from Week 26 (end of randomisation) to Week 78 (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after breakfast.
Time Frame week 26, week 78  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study drugs.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  191     173  
Change in Mean Postprandial Increment of Plasma Glucose After Breakfast, Weeks 26-78  
[units: mmol/L]
Mean ± Standard Deviation
  0.06  ± 2.827     0.72  ± 3.270  


Statistical Analysis 1 for Change in Mean Postprandial Increment of Plasma Glucose After Breakfast, Weeks 26-78
Groups [1] Liraglutide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] 0.7700
Mean [4] 0.06
Standard Deviation ± 2.827
95% Confidence Interval ( -0.344 to 0.463 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  A paired t test was made within the group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 – µ26 = 0 against HA: µ78 – µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change in Mean Postprandial Increment of Plasma Glucose After Breakfast, Weeks 26-78
Groups [1] Exenatide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] 0.0042
Mean [4] 0.72
Standard Deviation ± 3.270
95% Confidence Interval ( 0.230 to 1.212 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78– µ0=0 against HA: µ78 – µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



25.  Secondary:   Change in Mean Postprandial Increment of Plasma Glucose After Lunch, Weeks 26-78   [ Time Frame: week 26, week 78 ]

Measure Type Secondary
Measure Title Change in Mean Postprandial Increment of Plasma Glucose After Lunch, Weeks 26-78
Measure Description Change in mean postprandial increment of plasma glucose after lunch from Week 26 (end of randomisation) to Week 78 (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after lunch.
Time Frame week 26, week 78  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study drugs.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  191     173  
Change in Mean Postprandial Increment of Plasma Glucose After Lunch, Weeks 26-78  
[units: mmol/L]
Mean ± Standard Deviation
  0.67  ± 3.041     -0.09  ± 2.989  


Statistical Analysis 1 for Change in Mean Postprandial Increment of Plasma Glucose After Lunch, Weeks 26-78
Groups [1] Liraglutide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] 0.0026
Mean [4] 0.67
Standard Deviation ± 3.041
95% Confidence Interval ( 0.238 to 1.106 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  A paired t test was made within the group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 – µ26 = 0 against HA: µ78 – µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change in Mean Postprandial Increment of Plasma Glucose After Lunch, Weeks 26-78
Groups [1] Exenatide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] 0.6845
Mean [4] -0.09
Standard Deviation ± 2.989
95% Confidence Interval ( -0.541 to 0.356 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  A paired t test was made within the treatment group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 – µ26 = 0 against HA: µ78 – µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



26.  Secondary:   Change in Mean Postprandial Increment of Plasma Glucose After Dinner, Weeks 26-78   [ Time Frame: week 26, week 78 ]

Measure Type Secondary
Measure Title Change in Mean Postprandial Increment of Plasma Glucose After Dinner, Weeks 26-78
Measure Description Change in mean postprandial increment of plasma glucose after dinner from Week 26 (end of randomisation) to Week 78 (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after dinner.
Time Frame week 26, week 78  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study drugs.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  191     172  
Change in Mean Postprandial Increment of Plasma Glucose After Dinner, Weeks 26-78  
[units: mmol/L]
Mean ± Standard Deviation
  0.32  ± 2.705     0.58  ± 3.114  


Statistical Analysis 1 for Change in Mean Postprandial Increment of Plasma Glucose After Dinner, Weeks 26-78
Groups [1] Liraglutide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] 0.1041
Mean [4] 0.32
Standard Deviation ± 2.705
95% Confidence Interval ( -0.066 to 0.706 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  A paired t test was made within the group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 – µ26 = 0 against HA: µ78 – µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change in Mean Postprandial Increment of Plasma Glucose After Dinner, Weeks 26-78
Groups [1] Exenatide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] 0.0151
Mean [4] 0.58
Standard Deviation ± 3.114
95% Confidence Interval ( 0.114 to 1.052 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  A paired t test was made within the treatment group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 – µ26 = 0 against HA: µ78 – µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



27.  Secondary:   Change in Mean Postprandial Increment of Plasma Glucose After Breakfast at Week 78   [ Time Frame: week 0, week 78 ]

Measure Type Secondary
Measure Title Change in Mean Postprandial Increment of Plasma Glucose After Breakfast at Week 78
Measure Description Change in mean postprandial increment of plasma glucose after breakfast from baseline (week 0) to 78 weeks (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after breakfast.
Time Frame week 0, week 78  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study drugs.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  192     168  
Change in Mean Postprandial Increment of Plasma Glucose After Breakfast at Week 78  
[units: mmol/L]
Mean ± Standard Deviation
  -3.31  ± 3.857     -3.13  ± 3.560  


Statistical Analysis 1 for Change in Mean Postprandial Increment of Plasma Glucose After Breakfast at Week 78
Groups [1] Liraglutide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] <0.0001
Mean [4] -3.31
Standard Deviation ± 3.857
95% Confidence Interval ( -3.861 to -2.763 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78– µ0=0 against HA: µ78 – µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change in Mean Postprandial Increment of Plasma Glucose After Breakfast at Week 78
Groups [1] Exenatide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] <0.0001
Mean [4] -3.13
Standard Deviation ± 3.560
95% Confidence Interval ( -3.673 to -2.589 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78– µ0=0 against HA: µ78 – µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



28.  Secondary:   Change in Mean Postprandial Increment of Plasma Glucose After Lunch at Week 78   [ Time Frame: week 0, week 78 ]

Measure Type Secondary
Measure Title Change in Mean Postprandial Increment of Plasma Glucose After Lunch at Week 78
Measure Description Change in mean postprandial increment of plasma glucose after lunch from baseline (week 0) to 78 weeks (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after lunch.
Time Frame week 0, week 78  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study drugs.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  192     168  
Change in Mean Postprandial Increment of Plasma Glucose After Lunch at Week 78  
[units: mmol/L]
Mean ± Standard Deviation
  -1.93  ± 3.703     -2.17  ± 3.654  


Statistical Analysis 1 for Change in Mean Postprandial Increment of Plasma Glucose After Lunch at Week 78
Groups [1] Liraglutide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] <0.0001
Mean [4] -1.93
Standard Deviation ± 3.703
95% Confidence Interval ( -2.457 to -1.403 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78– µ0=0 against HA: µ78 – µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change in Mean Postprandial Increment of Plasma Glucose After Lunch at Week 78
Groups [1] Exenatide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] <0.0001
Mean [4] -2.17
Standard Deviation ± 3.654
95% Confidence Interval ( -2.731 to -1.618 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78– µ0=0 against HA: µ78 – µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



29.  Secondary:   Change in Mean Postprandial Increment of Plasma Glucose After Dinner at Week 78   [ Time Frame: week 0, week 78 ]

Measure Type Secondary
Measure Title Change in Mean Postprandial Increment of Plasma Glucose After Dinner at Week 78
Measure Description Change in mean postprandial increment of plasma glucose after dinner from baseline (week 0) to 78 weeks (end of treatment). Prandial increments of plasma glucose were calculated as the difference between plasma glucose values measured before and after dinner.
Time Frame week 0, week 78  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study drugs.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  191     167  
Change in Mean Postprandial Increment of Plasma Glucose After Dinner at Week 78  
[units: mmol/L]
Mean ± Standard Deviation
  -2.21  ± 3.752     -2.55  ± 3.625  


Statistical Analysis 1 for Change in Mean Postprandial Increment of Plasma Glucose After Dinner at Week 78
Groups [1] Liraglutide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] <0.0001
Mean [4] -2.21
Standard Deviation ± 3.752
95% Confidence Interval ( -2.747 to -1.676 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78– µ0=0 against HA: µ78 – µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change in Mean Postprandial Increment of Plasma Glucose After Dinner at Week 78
Groups [1] Exenatide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] <0.0001
Mean [4] -2.55
Standard Deviation ± 3.625
95% Confidence Interval ( -3.104 to -1.997 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78– µ0=0 against HA: µ78 – µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



30.  Secondary:   Change in Beta-cell Function at Week 26   [ Time Frame: week 0, week 26 ]

Measure Type Secondary
Measure Title Change in Beta-cell Function at Week 26
Measure Description

Change in Beta-cell function from baseline (week 0) to 26 weeks (end of randomisation). Beta-cell function was derived from fasting plasma glucose (FPG) and fasting insulin concentrations using the homeostasic model assessment (HOMA) method which uses the assumption that normal-weight normal subjects aged under 35 years have a 100% beta-cell function (HOMA-B).

Beta-cell function: HOMA-B (%) = 20∙fasting insulin[uU/mL] divided by (FPG mmol/L]‑3.5).

Time Frame week 0, week 26  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects exposed to study drug.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  214     214  
Change in Beta-cell Function at Week 26  
[units: percentage point (%point)]
Least Squares Mean ± Standard Error
  32.12  ± 6.75     2.74  ± 6.75  


Statistical Analysis 1 for Change in Beta-cell Function at Week 26
Groups [1] All groups
Method [2] ANCOVA
P Value [3] <.0001
Estimated treatment difference, LS Mean [4] 29.37
95% Confidence Interval ( 16.81 to 41.93 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  ANCOVA model included treatment, country and previous treatment as fixed effects and baseline value of the endpoint as covariate. The objective was to demonstrate that treatment with liraglutide was different from treatment with exenatide. Thus the null hypothesis and its alternative were H0: µliraglutide = µexenatide against HA1:µliraglutide ≠ µexenatide where µliraglutide and µexenatide is the mean value of the endpoint in the liraglutide arm and exenatide arm, respectively.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  There were no multiplicity concerns.
[4] Other relevant estimation information:
  No text entered.



31.  Secondary:   Change in Beta-cell Function, Weeks 26-78   [ Time Frame: week 26, week 78 ]

Measure Type Secondary
Measure Title Change in Beta-cell Function, Weeks 26-78
Measure Description

Change in Beta-cell function from Week 26 (end of randomisation) to Week 78 (end of treatment). Beta-cell function was derived from fasting plasma glucose (FPG) and fasting insulin concentrations using the homeostasic model assessment (HOMA) method which uses the assumption that normal-weight normal subjects aged under 35 years have a 100% beta-cell function (HOMA-B).

Beta-cell function: HOMA-B (%) = 20∙fasting insulin[uU/mL] divided by (FPG mmol/L]‑3.5).

Time Frame week 26, week 78  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study drugs.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  198     179  
Change in Beta-cell Function, Weeks 26-78  
[units: percentage point (%point)]
Mean ± Standard Deviation
  -18.18  ± 62.811     2.29  ± 52.997  


Statistical Analysis 1 for Change in Beta-cell Function, Weeks 26-78
Groups [1] Liraglutide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] <0.0001
Mean [4] -18.18
Standard Deviation ± 62.811
95% Confidence Interval ( -26.988 to -9.382 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  A paired t test was made within the group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 – µ26 = 0 against HA: µ78 – µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change in Beta-cell Function, Weeks 26-78
Groups [1] Exenatide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] 0.5304
Mean [4] 2.49
Standard Deviation ± 52.997
95% Confidence Interval ( -5.327 to 10.307 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  A paired t test was made within the treatment group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 – µ26 = 0 against HA: µ78 – µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



32.  Secondary:   Change in Beta-cell Function at Week 78   [ Time Frame: week 0, week 78 ]

Measure Type Secondary
Measure Title Change in Beta-cell Function at Week 78
Measure Description

Change in Beta-cell function from baseline (week 0) to 78 weeks (end of treatment). Beta-cell function was derived from fasting plasma glucose (FPG) and fasting insulin concentrations using the homeostasic model assessment (HOMA) method which uses the assumption that normal-weight normal subjects aged under 35 years have a 100% beta-cell function (HOMA-B).

Beta-cell function: HOMA-B (%) = 20∙fasting insulin[uU/mL] divided by (FPG mmol/L]‑3.5).

Time Frame week 0, week 78  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study drugs.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  189     176  
Change in Beta-cell Function at Week 78  
[units: percentage point (%point)]
Mean ± Standard Deviation
  24.86  ± 59.326     11.13  ± 87.145  


Statistical Analysis 1 for Change in Beta-cell Function at Week 78
Groups [1] Liraglutide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] <0.0001
Mean [4] 24.86
Standard Deviation ± 59.326
95% Confidence Interval ( 16.348 to 33.374 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78– µ0=0 against HA: µ78 – µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change in Beta-cell Function at Week 78
Groups [1] Exenatide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] 0.0920
Mean [4] 11.13
Standard Deviation ± 87.145
95% Confidence Interval ( -1.835 to 24.093 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78– µ0=0 against HA: µ78 – µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



33.  Secondary:   Change in Total Cholesterol at Week 26   [ Time Frame: week 0, week 26 ]

Measure Type Secondary
Measure Title Change in Total Cholesterol at Week 26
Measure Description Change in total cholesterol (TC) from baseline (week 0) to 26 weeks (end of randomisation)
Time Frame week 0, week 26  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects exposed to study drug.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  226     220  
Change in Total Cholesterol at Week 26  
[units: mmol/L]
Least Squares Mean ± Standard Error
  -0.20  ± 0.07     -0.09  ± 0.07  


Statistical Analysis 1 for Change in Total Cholesterol at Week 26
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.0946
Estimated treatment difference, LS Mean [4] -0.11
95% Confidence Interval ( -0.23 to 0.02 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  ANCOVA model included treatment, country and previous treatment as fixed effects and baseline value of the endpoint as covariate. The objective was to demonstrate that treatment with liraglutide was different from treatment with exenatide. Thus the null hypothesis and its alternative were H0: µliraglutide = µexenatide against HA1:µliraglutide ≠ µexenatide where µliraglutide and µexenatide is the mean value of the endpoint in the liraglutide arm and exenatide arm, respectively.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  There were no multiplicity concerns.
[4] Other relevant estimation information:
  No text entered.



34.  Secondary:   Change in Total Cholesterol, Weeks 26-78   [ Time Frame: week 26, week 78 ]

Measure Type Secondary
Measure Title Change in Total Cholesterol, Weeks 26-78
Measure Description Change in total cholesterol (TC) from Week 26 (end of randomisation) to Week 78 (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group).
Time Frame week 26, week 78  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the trial products.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  199     184  
Change in Total Cholesterol, Weeks 26-78  
[units: mmol/L]
Mean ± Standard Deviation
  0.11  ± 0.774     0.12  ± 0.804  


Statistical Analysis 1 for Change in Total Cholesterol, Weeks 26-78
Groups [1] Liraglutide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] 0.0513
Mean [4] 0.11
Standard Deviation ± 0.774
95% Confidence Interval ( -0.001 to 0.216 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  A paired t test was made within the group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 – µ26 = 0 against HA: µ78 – µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change in Total Cholesterol, Weeks 26-78
Groups [1] Exenatide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] 0.0513
Mean [4] 0.12
Standard Deviation ± 0.804
95% Confidence Interval ( -0.001 to 0.233 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  A paired t test was made within the group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 – µ26 = 0 against HA: µ78 – µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



35.  Secondary:   Change in Total Cholesterol at Week 78   [ Time Frame: week 0, week 78 ]

Measure Type Secondary
Measure Title Change in Total Cholesterol at Week 78
Measure Description Change in total cholesterol (TC) from baseline (week 0) to 78 weeks (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group).
Time Frame week 0, week 78  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study products.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  198     183  
Change in Total Cholesterol at Week 78  
[units: mmol/L]
Mean ± Standard Deviation
  -0.07  ± 0.859     0.09  ± 0.890  


Statistical Analysis 1 for Change in Total Cholesterol at Week 78
Groups [1] Liraglutide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] 0.2764
Mean [4] -0.07
Standard Deviation ± 0.859
95% Confidence Interval ( -0.187 to 0.054 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78– µ0=0 against HA: µ78 – µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change in Total Cholesterol at Week 78
Groups [1] Exenatide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] 0.1911
Mean [4] 0.09
Standard Deviation ± 0.890
95% Confidence Interval ( -0.043 to 0.216 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78– µ0=0 against HA: µ78 – µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



36.  Secondary:   Change in Low-density Lipoprotein-cholesterol at Week 26   [ Time Frame: week 0, week 26 ]

Measure Type Secondary
Measure Title Change in Low-density Lipoprotein-cholesterol at Week 26
Measure Description Change in Low-density Lipoprotein-cholesterol (LDL-C) from baseline (week 0) to 26 weeks (end of randomisation)
Time Frame week 0, week 26  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects exposed to study drug.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  219     215  
Change in Low-density Lipoprotein-cholesterol at Week 26  
[units: mmol/L]
Least Squares Mean ± Standard Error
  -0.44  ± 0.06     -0.40  ± 0.06  


Statistical Analysis 1 for Change in Low-density Lipoprotein-cholesterol at Week 26
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.4412
Estimated treatment difference, LS Mean [4] -0.04
95% Confidence Interval ( -0.15 to 0.06 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  ANCOVA model included treatment, country and previous treatment as fixed effects and baseline value of the endpoint as covariate. The objective was to demonstrate that treatment with liraglutide was different from treatment with exenatide. Thus the null hypothesis and its alternative were H0: µliraglutide = µexenatide against HA1:µliraglutide ≠ µexenatide where µliraglutide and µexenatide is the mean value of the endpoint in the liraglutide arm and exenatide arm, respectively.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  There were no multiplicity concerns.
[4] Other relevant estimation information:
  No text entered.



37.  Secondary:   Change in Low-density Lipoprotein-cholesterol, Weeks 26-78   [ Time Frame: week 26, week 78 ]

Measure Type Secondary
Measure Title Change in Low-density Lipoprotein-cholesterol, Weeks 26-78
Measure Description Change in low-density lipoprotein-cholesterol (LDL-C) from Week 26 (end of randomisation) to Week 78 (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group).
Time Frame week 26, week 78  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study products.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  199     180  
Change in Low-density Lipoprotein-cholesterol, Weeks 26-78  
[units: mmol/L]
Mean ± Standard Deviation
  0.03  ± 0.606     0.08  ± 0.720  


Statistical Analysis 1 for Change in Low-density Lipoprotein-cholesterol, Weeks 26-78
Groups [1] Liraglutide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] 0.4746
Mean [4] 0.03
Standard Deviation ± 0.606
95% Confidence Interval ( -0.054 to 0.115 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  A paired t test was made within the group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 – µ26 = 0 against HA: µ78 – µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change in Low-density Lipoprotein-cholesterol, Weeks 26-78
Groups [1] Exenatide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] 0.1281
Mean [4] 0.08
Standard Deviation ± 0.720
95% Confidence Interval ( -0.024 to 0.188 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  A paired t test was made within the treatment group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 – µ26 = 0 against HA: µ78 – µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



38.  Secondary:   Change in Low-density Lipoprotein-cholesterol at Week 78   [ Time Frame: week 0, week 78 ]

Measure Type Secondary
Measure Title Change in Low-density Lipoprotein-cholesterol at Week 78
Measure Description Change in Low-density Lipoprotein-cholesterol (LDL-C) from baseline (week 0) to 78 weeks (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group).
Time Frame week 0, week 78  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study products.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  183     176  
Change in Low-density Lipoprotein-cholesterol at Week 78  
[units: mmol/L]
Mean ± Standard Deviation
  -0.30  ± 0.604     -0.21  ± 0.647  


Statistical Analysis 1 for Change in Low-density Lipoprotein-cholesterol at Week 78
Groups [1] Liraglutide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] <0.0001
Mean [4] -0.30
Standard Deviation ± 0.604
95% Confidence Interval ( -0.390 to -0.214 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78– µ0=0 against HA: µ78 – µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change in Low-density Lipoprotein-cholesterol at Week 78
Groups [1] Exenatide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] <0.0001
Mean [4] -0.21
Standard Deviation ± 0.647
95% Confidence Interval ( -0.303 to -0.110 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78– µ0=0 against HA: µ78 – µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



39.  Secondary:   Change in Very Low-density Lipoprotein-cholesterol at Week 26   [ Time Frame: week 0, week 26 ]

Measure Type Secondary
Measure Title Change in Very Low-density Lipoprotein-cholesterol at Week 26
Measure Description Change in very low-density lipoprotein-cholesterol (VLDL-C) from baseline (week 0) to 26 weeks (end of randomisation)
Time Frame week 0, week 26  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects exposed to study drug.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  216     212  
Change in Very Low-density Lipoprotein-cholesterol at Week 26  
[units: mmol/L]
Least Squares Mean ± Standard Error
  0.20  ± 0.04     0.27  ± 0.04  


Statistical Analysis 1 for Change in Very Low-density Lipoprotein-cholesterol at Week 26
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.0277
Estimated treatment difference, LS Mean [4] -0.07
95% Confidence Interval ( -0.13 to -0.01 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  ANCOVA model included treatment, country and previous treatment as fixed effects and baseline value of the endpoint as covariate. The objective was to demonstrate that treatment with liraglutide was different from treatment with exenatide. Thus the null hypothesis and its alternative were H0: µliraglutide = µexenatide against HA1:µliraglutide ≠ µexenatide where µliraglutide and µexenatide is the mean value of the endpoint in the liraglutide arm and exenatide arm, respectively.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  There were no multiplicity concerns.
[4] Other relevant estimation information:
  No text entered.



40.  Secondary:   Change in Very Low-density Lipoprotein-cholesterol, Weeks 26-78   [ Time Frame: week 26, week 78 ]

Measure Type Secondary
Measure Title Change in Very Low-density Lipoprotein-cholesterol, Weeks 26-78
Measure Description Change in Very Low-density Lipoprotein-cholesterol (VLDL-C) from Week 26 (end of randomisation) to Week 78 (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group).
Time Frame week 26, week 78  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study products.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  199     180  
Change in Very Low-density Lipoprotein-cholesterol, Weeks 26-78  
[units: mmol/L]
Mean ± Standard Deviation
  0.06  ± 0.290     0.03  ± 0.307  


Statistical Analysis 1 for Change in Very Low-density Lipoprotein-cholesterol, Weeks 26-78
Groups [1] Liraglutide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] 0.0030
Mean [4] 0.06
Standard Deviation ± 0.290
95% Confidence Interval ( 0.021 to 0.102 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  A paired t test was made within the group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 – µ26 = 0 against HA: µ78 – µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change in Very Low-density Lipoprotein-cholesterol, Weeks 26-78
Groups [1] Exenatide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] 0.1452
Mean [4] 0.03
Standard Deviation ± 0.307
95% Confidence Interval ( -0.012 to 0.079 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  A paired t test was made within the treatment group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 – µ26 = 0 against HA: µ78 – µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



41.  Secondary:   Change in Very Low-density Lipoprotein-cholesterol at Week 78   [ Time Frame: week 0, week 78 ]

Measure Type Secondary
Measure Title Change in Very Low-density Lipoprotein-cholesterol at Week 78
Measure Description Change in Very Low-density Lipoprotein-cholesterol (VLDL-C) from baseline (week 0) to 78 weeks (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group).
Time Frame week 0, week 78  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study products.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  173     168  
Change in Very Low-density Lipoprotein-cholesterol at Week 78  
[units: mmol/L]
Mean ± Standard Deviation
  0.27  ± 0.306     0.31  ± 0.346  


Statistical Analysis 1 for Change in Very Low-density Lipoprotein-cholesterol at Week 78
Groups [1] Liraglutide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] <0.0001
Mean [4] 0.27
Standard Deviation ± 0.306
95% Confidence Interval ( 0.223 to 0.315 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78– µ0=0 against HA: µ78 – µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change in Very Low-density Lipoprotein-cholesterol at Week 78
Groups [1] Exenatide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] <0.0001
Mean [4] 0.31
Standard Deviation ± 0.346
95% Confidence Interval ( 0.259 to 0.364 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78– µ0=0 against HA: µ78 – µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



42.  Secondary:   Change in High-density Lipoprotein-cholesterol at Week 26   [ Time Frame: week 0, week 26 ]

Measure Type Secondary
Measure Title Change in High-density Lipoprotein-cholesterol at Week 26
Measure Description Change in High-density Lipoprotein-cholesterol (HDL-C) from baseline (week 0) to 26 weeks (end of randomisation)
Time Frame week 0, week 26  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects exposed to study drug.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  226     220  
Change in High-density Lipoprotein-cholesterol at Week 26  
[units: mmol/L]
Least Squares Mean ± Standard Error
  -0.04  ± 0.02     -0.05  ± 0.02  


Statistical Analysis 1 for Change in High-density Lipoprotein-cholesterol at Week 26
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.5105
Estimated treatment difference, LS Mean [4] 0.01
95% Confidence Interval ( -0.02 to 0.04 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  ANCOVA model included treatment, country and previous treatment as fixed effects and baseline value of the endpoint as covariate. The objective was to demonstrate that treatment with liraglutide was different from treatment with exenatide. Thus the null hypothesis and its alternative were H0: µliraglutide = µexenatide against HA1:µliraglutide ≠ µexenatide where µliraglutide and µexenatide is the mean value of the endpoint in the liraglutide arm and exenatide arm, respectively.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  There were no multiplicity concerns.
[4] Other relevant estimation information:
  No text entered.



43.  Secondary:   Change in High-density Lipoprotein-cholesterol, Weeks 26-78   [ Time Frame: week 26, week 78 ]

Measure Type Secondary
Measure Title Change in High-density Lipoprotein-cholesterol, Weeks 26-78
Measure Description Change in High-density Lipoprotein-cholesterol (HDL-C) from Week 26 (end of randomisation) to Week 78 (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group).
Time Frame week 26, week 78  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study products.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  119     180  
Change in High-density Lipoprotein-cholesterol, Weeks 26-78  
[units: mmol/L]
Mean ± Standard Deviation
  -0.01  ± 0.150     0.00  ± 0.141  


Statistical Analysis 1 for Change in High-density Lipoprotein-cholesterol, Weeks 26-78
Groups [1] Liraglutide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] 0.2220
Mean [4] -0.01
Standard Deviation ± 0.150
95% Confidence Interval ( -0.034 to 0.008 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  A paired t test was made within the group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 – µ26 = 0 against HA: µ78 – µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change in High-density Lipoprotein-cholesterol, Weeks 26-78
Groups [1] Exenatide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] 0.7923
Mean [4] 0.00
Standard Deviation ± 0.141
95% Confidence Interval ( -0.018 to 0.024 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  A paired t test was made within the treatment group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 – µ26 = 0 against HA: µ78 – µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



44.  Secondary:   Change in High-density Lipoprotein-cholesterol at Week 78   [ Time Frame: week 0, week 78 ]

Measure Type Secondary
Measure Title Change in High-density Lipoprotein-cholesterol at Week 78
Measure Description Change in High-density Lipoprotein-cholesterol (HDL-C) from baseline (week 0) to 78 weeks (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group).
Time Frame week 0, week 78  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study products.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  183     176  
Change in High-density Lipoprotein-cholesterol at Week 78  
[units: mmol/L]
Mean ± Standard Deviation
  -0.03  ± 0.159     -0.02  ± 0.165  


Statistical Analysis 1 for Change in High-density Lipoprotein-cholesterol at Week 78
Groups [1] Liraglutide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] 0.0254
Mean [4] -0.03
Standard Deviation ± 0.159
95% Confidence Interval ( -0.050 to -0.003 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78– µ0=0 against HA: µ78 – µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change in High-density Lipoprotein-cholesterol at Week 78
Groups [1] Exenatide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] 0.2244
Mean [4] -0.02
Standard Deviation ± 0.165
95% Confidence Interval ( -0.040 to 0.009 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78– µ0=0 against HA: µ78 – µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



45.  Secondary:   Change in Triglyceride at Week 26   [ Time Frame: week 0, week 26 ]

Measure Type Secondary
Measure Title Change in Triglyceride at Week 26
Measure Description Change in triglyceride (TG) from from baseline (week 0) to 26 weeks (end of randomisation)
Time Frame week 0, week 26  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects exposed to study drug.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  225     220  
Change in Triglyceride at Week 26  
[units: mmol/L]
Least Squares Mean ± Standard Error
  -0.41  ± 0.10     -0.23  ± 0.10  


Statistical Analysis 1 for Change in Triglyceride at Week 26
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.0485
Estimated treatment difference, LS Mean [4] -0.18
95% Confidence Interval ( -0.37 to -0.00 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  ANCOVA model included treatment, country and previous treatment as fixed effects and baseline value of the endpoint as covariate. The objective was to demonstrate that treatment with liraglutide was different from treatment with exenatide. Thus the null hypothesis and its alternative were H0: µliraglutide = µexenatide against HA1:µliraglutide ≠ µexenatide where µliraglutide and µexenatide is the mean value of the endpoint in the liraglutide arm and exenatide arm, respectively.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  There were no multiplicity concerns.
[4] Other relevant estimation information:
  No text entered.



46.  Secondary:   Change in Triglyceride, Weeks 26-78   [ Time Frame: week 26, week 78 ]

Measure Type Secondary
Measure Title Change in Triglyceride, Weeks 26-78
Measure Description Change in Triglyceride (TG) from Week 26 (end of randomisation) to Week 78 (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group).
Time Frame week 26, week 78  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study products.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  198     184  
Change in Triglyceride, Weeks 26-78  
[units: mmol/L]
Mean ± Standard Deviation
  0.1  ± 0.82     -0.0  ± 0.96  


Statistical Analysis 1 for Change in Triglyceride, Weeks 26-78
Groups [1] Liraglutide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] 0.1161
Mean [4] 0.1
Standard Deviation ± 0.82
95% Confidence Interval ( -0.02 to 0.21 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  A paired t test was made within the group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 – µ26 = 0 against HA: µ78 – µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change in Triglyceride, Weeks 26-78
Groups [1] Exenatide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] 0.7888
Mean [4] -0.0
Standard Deviation ± 0.96
95% Confidence Interval ( -0.16 to 0.12 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  A paired t test was made within the treatment group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 – µ26 = 0 against HA: µ78 – µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



47.  Secondary:   Change in Triglyceride at Week 78   [ Time Frame: week 0, week 78 ]

Measure Type Secondary
Measure Title Change in Triglyceride at Week 78
Measure Description Change in triglyceride (TG) from baseline (week 0) to 78 weeks (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group).
Time Frame week 0, week 78  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study products.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  198     183  
Change in Triglyceride at Week 78  
[units: mmol/L]
Mean ± Standard Deviation
  -0.3  ± 1.07     -0.1  ± 1.47  


Statistical Analysis 1 for Change in Triglyceride at Week 78
Groups [1] Liraglutide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] 0.0003
Mean [4] -0.3
Standard Deviation ± 1.07
95% Confidence Interval ( -0.43 to -0.13 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78– µ0=0 against HA: µ78 – µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change in Triglyceride at Week 78
Groups [1] Exenatide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] 0.2078
Mean [4] -0.1
Standard Deviation ± 1.47
95% Confidence Interval ( -0.35 to 0.08 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78– µ0=0 against HA: µ78 – µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



48.  Secondary:   Change in Free Fatty Acid at Week 26   [ Time Frame: week 0, week 26 ]

Measure Type Secondary
Measure Title Change in Free Fatty Acid at Week 26
Measure Description Change in Free Fatty Acid (FFA) from baseline (week 0) to 26 weeks (end of randomisation)
Time Frame week 0, week 26  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects exposed to study drug.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  220     222  
Change in Free Fatty Acid at Week 26  
[units: mmol/L]
Least Squares Mean ± Standard Error
  -0.17  ± 0.02     -0.10  ± 0.02  


Statistical Analysis 1 for Change in Free Fatty Acid at Week 26
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.0014
Estimated treatment difference, LS Mean [4] -0.07
95% Confidence Interval ( -0.11 to -0.03 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  ANCOVA model included treatment, country and previous treatment as fixed effects and baseline value of the endpoint as covariate. The objective was to demonstrate that treatment with liraglutide was different from treatment with exenatide. Thus the null hypothesis and its alternative were H0: µliraglutide = µexenatide against HA1:µliraglutide ≠ µexenatide where µliraglutide and µexenatide is the mean value of the endpoint in the liraglutide arm and exenatide arm, respectively.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  There were no multiplicity concerns.
[4] Other relevant estimation information:
  No text entered.



49.  Secondary:   Change in Free Fatty Acid, Weeks 26-78   [ Time Frame: week 26, week 78 ]

Measure Type Secondary
Measure Title Change in Free Fatty Acid, Weeks 26-78
Measure Description Change in Free Fatty Acid (FFA) from Week 26 (end of randomisation) to Week 78 (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group).
Time Frame week 26, week 78  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study products.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  199     182  
Change in Free Fatty Acid, Weeks 26-78  
[units: mmol/L]
Mean ± Standard Deviation
  0.06  ± 0.269     0.01  ± 0.272  


Statistical Analysis 1 for Change in Free Fatty Acid, Weeks 26-78
Groups [1] Liraglutide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] 0.0018
Mean [4] 0.06
Standard Deviation ± 0.269
95% Confidence Interval ( 0.023 to 0.098 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  A paired t test was made within the group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 – µ26 = 0 against HA: µ78 – µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change in Free Fatty Acid, Weeks 26-78
Groups [1] Exenatide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] 0.5499
Mean [4] 0.01
Standard Deviation ± 0.272
95% Confidence Interval ( -0.028 to 0.052 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  A paired t test was made within the treatment group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 – µ26 = 0 against HA: µ78 – µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



50.  Secondary:   Change in Free Fatty Acid at Week 78   [ Time Frame: week 0, week 78 ]

Measure Type Secondary
Measure Title Change in Free Fatty Acid at Week 78
Measure Description Change in Free Fatty Acid (FFA) from baseline (week 0) to 78 weeks (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group).
Time Frame week 0, week 78  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study products.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  195     182  
Change in Free Fatty Acid at Week 78  
[units: mmol/L]
Mean ± Standard Deviation
  -0.10  ± 0.273     -0.07  ± 0.302  


Statistical Analysis 1 for Change in Free Fatty Acid at Week 78
Groups [1] Liraglutide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] <0.0001
Mean [4] -0.10
Standard Deviation ± 0.273
95% Confidence Interval ( -0.140 to -0.062 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78– µ0=0 against HA: µ78 – µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change in Free Fatty Acid at Week 78
Groups [1] Exenatide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] 0.0012
Mean [4] -0.07
Standard Deviation ± 0.302
95% Confidence Interval ( -0.118 to -0.030 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  A paired t test was made within the treatment group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 – µ26 = 0 against HA: µ78 – µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



51.  Secondary:   Change in Apolipoprotein B at Week 26   [ Time Frame: week 0, week 26 ]

Measure Type Secondary
Measure Title Change in Apolipoprotein B at Week 26
Measure Description Change in apolipoprotein B (ApoB) from baseline (week 0) to 26 weeks (end of randomisation)
Time Frame week 0, week 26  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects exposed to study drug.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  226     222  
Change in Apolipoprotein B at Week 26  
[units: g/L]
Least Squares Mean ± Standard Error
  -0.06  ± 0.02     -0.03  ± 0.02  


Statistical Analysis 1 for Change in Apolipoprotein B at Week 26
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.1119
Estimated treatment difference, LS Mean [4] -0.02
95% Confidence Interval ( -0.05 to 0.01 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  ANCOVA model included treatment, country and previous treatment as fixed effects and baseline value of the endpoint as covariate. The objective was to demonstrate that treatment with liraglutide was different from treatment with exenatide. Thus the null hypothesis and its alternative were H0: µliraglutide = µexenatide against HA1:µliraglutide ≠ µexenatide where µliraglutide and µexenatide is the mean value of the endpoint in the liraglutide arm and exenatide arm, respectively.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  There were no multiplicity concerns.
[4] Other relevant estimation information:
  No text entered.



52.  Secondary:   Change in Apolipoprotein B, Weeks 26-78   [ Time Frame: week 26, week 78 ]

Measure Type Secondary
Measure Title Change in Apolipoprotein B, Weeks 26-78
Measure Description Change in apolipoprotein B (ApoB) from Week 26 (end of randomisation) to Week 78 (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group).
Time Frame week 26, week 78  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study products.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  199     184  
Change in Apolipoprotein B, Weeks 26-78  
[units: g/L]
Mean ± Standard Deviation
  -0.02  ± 0.168     -0.03  ± 0.189  


Statistical Analysis 1 for Change in Apolipoprotein B, Weeks 26-78
Groups [1] Liraglutide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] 0.1342
Mean [4] -0.02
Standard Deviation ± 0.168
95% Confidence Interval ( -0.041 to 0.006 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  A paired t test was made within the group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 – µ26 = 0 against HA: µ78 – µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change in Apolipoprotein B, Weeks 26-78
Groups [1] Exenatide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] 0.0344
Mean [4] -0.03
Standard Deviation ± 0.189
95% Confidence Interval ( -0.057 to -0.002 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  A paired t test was made within the treatment group and 95% confidence intervals for the difference between Weeks 26 and 78 were constructed. H0 was µ78 – µ26 = 0 against HA: µ78 – µ26 ≠ 0. A difference between the two means (Week 26 and Week 78) was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



53.  Secondary:   Change in Apolipoprotein B at Week 78   [ Time Frame: week 0, week 78 ]

Measure Type Secondary
Measure Title Change in Apolipoprotein B at Week 78
Measure Description Change in apolipoprotein B (ApoB) from baseline (week 0) to 78 weeks (end of treatment) within each treatment group (the liraglutide -> liraglutide group and the exenatide -> liraglutide group).
Time Frame week 0, week 78  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intention to Treat (ITT) analysis set using LOCF (Last Observation Carried Forward) is all randomised subjects who entered the extension period and who had been exposed to at least one dose of the study products.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  198     184  
Change in Apolipoprotein B at Week 78  
[units: g/L]
Mean ± Standard Deviation
  -0.08  ± 0.176     -0.07  ± 0.192  


Statistical Analysis 1 for Change in Apolipoprotein B at Week 78
Groups [1] Liraglutide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] <0.0001
Mean [4] -0.08
Standard Deviation ± 0.176
95% Confidence Interval ( -0.105 to -0.056 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78– µ0=0 against HA: µ78 – µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change in Apolipoprotein B at Week 78
Groups [1] Exenatide -> Liraglutide -> Liraglutide
Method [2] Paired t test
P Value [3] <0.0001
Mean [4] -0.07
Standard Deviation ± 0.192
95% Confidence Interval ( -0.094 to -0.038 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analysis was made with a paired t test within the treatment group and 95% CIs for the difference between Weeks 0 and 78 were constructed. H0 was µ78– µ0=0 against HA: µ78 – µ0 ≠ 0. A difference between the two means was concluded when H0 was rejected at the 5% level.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



54.  Secondary:   Hypoglycaemic Episodes at Week 26   [ Time Frame: weeks 0-26 ]

Measure Type Secondary
Measure Title Hypoglycaemic Episodes at Week 26
Measure Description Total number of hypoglycaemic episodes occurring after baseline (week 0) and until week 26 (end of randomisation). Hypoglycaemic episodes were defined as major, minor, or symptoms only. Major if the subject was unable to treat her/himself. Minor if subject was able to treat her/himself and plasma glucose was below 3.1 mmol/L. Symptoms only if subject was able to treat her/himself and with no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L.
Time Frame weeks 0-26  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The safety analysis set is all subjects who had been exposed to at least one dose of the study products.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  235     232  
Hypoglycaemic Episodes at Week 26  
[units: episodes]
   
Major     0     2  
Minor     208     264  
Symptoms only     79     93  

No statistical analysis provided for Hypoglycaemic Episodes at Week 26



55.  Secondary:   Hypoglyceamic Episodes, Weeks 26-78   [ Time Frame: weeks 26-78 ]

Measure Type Secondary
Measure Title Hypoglyceamic Episodes, Weeks 26-78
Measure Description Total number of hypoglycaemic episodes occurring after end of randomisation (week 26) and until week 78 (end of treatment). Hypoglycaemic episodes were defined as major, minor, or symptoms only. Major if the subject was unable to treat her/himself. Minor if subject was able to treat her/himself and plasma glucose was below 3.1 mmol/L. Symptoms only if subject was able to treat her/himself and with no plasma glucose measurement or plasma glucose higher than or equal to 3.1 mmol/L.
Time Frame weeks 26-78  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The safety analysis set is all subjects who had been exposed to at least one dose of the study products.

Reporting Groups
  Description
Liraglutide -> Liraglutide -> Liraglutide Liraglutide 1.8 mg once daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) continued to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)
Exenatide -> Liraglutide -> Liraglutide Exenatide 10 mcg twice daily + OAD (metformin monotherapy, sulphonylurea (SU) monotherapy or a combination), Weeks 0-26 (double-blinded) switched to receive liraglutide 1.8 mg once daily + OAD in extension period (weeks 26-52 and 52-78)

Measured Values
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Number of Participants Analyzed  
[units: participants]
  202     187  
Hypoglyceamic Episodes, Weeks 26-78  
[units: episodes]
   
Major     1     0  
Minor     140     172  
Symptoms only     37     32  

No statistical analysis provided for Hypoglyceamic Episodes, Weeks 26-78




  Serious Adverse Events


  Other Adverse Events


  More Information
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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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Public Access to Clinical Trials
Organization: Novo Nordisk A/S
e-mail: clinicaltrials@novonordisk.com


No publications provided by Novo Nordisk A/S

Publications automatically indexed to this study:


Responsible Party: Public Access to Clinical Trials, Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT00518882     History of Changes
Other Study ID Numbers: NN2211-1797, 2006-006092-21
Study First Received: August 20, 2007
Results First Received: February 23, 2010
Last Updated: June 19, 2012
Health Authority: United States: Food and Drug Administration
Finland: Finnish Medicines Agency
Switzerland: Swissmedic
Germany: Federal Institute for Drugs and Medical Devices
Ireland: Irish Medicines Board
Austria: Federal Ministry for Health and Women
Poland: The Office for Registration of Medicinal Products, Medical Devices; and Biocides, Central Evidence of Clinical Trials
Denmark: Danish Medicines Agency
Macedonia, The Former Yugoslav Republic of: Drug Agency, Ministry of Health
Slovenia: Agency of Drugs and Medicinal Products of the Slovenian Republic
Romania: National Medicines Agency
Sweden: Medical Products Agency