Efficacy of Once-Weekly Exenatide Versus Once or Twice Daily Insulin Detemir in Patients With Type 2 Diabetes

This study has been completed.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01003184
First received: October 15, 2009
Last updated: September 18, 2013
Last verified: September 2013
Results First Received: November 20, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Type 2 Diabetes Mellitus
Interventions: Drug: exenatide once weekly
Drug: insulin detemir

  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
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
6 patients who were enrolled and randomized, subsequently discontinued the study before receiving study drug. These patients were not included in analysis.

Reporting Groups
  Description
Exenatide Once Weekly Exenatide once weekly : subcutaneous injection, 2mg, once a week
Insulin Detemir Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day

Participant Flow:   Overall Study
    Exenatide Once Weekly     Insulin Detemir  
STARTED     111     111  
Full Analysis Set (FAS)     111     105  
COMPLETED     92     99  
NOT COMPLETED     19     12  
Adverse Event                 12                 5  
Lost to Follow-up                 1                 0  
Loss of glucose control                 1                 1  
Protocol Violation                 3                 0  
Withdrawal by Subject                 1                 6  
Physician Decision                 1                 0  



  Baseline Characteristics
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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
Exenatide Once Weekly Exenatide once weekly : subcutaneous injection, 2mg, once a week
Insulin Detemir Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day
Total Total of all reporting groups

Baseline Measures
    Exenatide Once Weekly     Insulin Detemir     Total  
Number of Participants  
[units: participants]
  111     105     216  
Age  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     74     78     152  
>=65 years     37     27     64  
Age  
[units: years]
Mean ± Standard Deviation
  59.2  ± 9.86     57.8  ± 9.48     58.5  ± 9.68  
Gender  
[units: participants]
     
Female     40     33     73  
Male     71     72     143  
HbA1c [1]
[units: Percentage of total hemoglobin]
Mean ± Standard Deviation
  8.4  ± 0.85     8.4  ± 0.88     8.4  ± 0.86  
Weight  
[units: Kilograms]
Mean ± Standard Deviation
  96.7  ± 17.03     97.9  ± 15.82     97.3  ± 16.42  
[1] At visit 3 (week 0).



  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   Percentage of Patients Achieving Glycosylated Hemoglobin (HbA1c) Concentration ≤7.0% With Weight Loss (≥1.0 kg) at Endpoint (Week 26)   [ Time Frame: Baseline, Week 26 ]

Measure Type Primary
Measure Title Percentage of Patients Achieving Glycosylated Hemoglobin (HbA1c) Concentration ≤7.0% With Weight Loss (≥1.0 kg) at Endpoint (Week 26)
Measure Description The primary endpoint is the percentage of patients achieving HbA1c concentration ≤7.0% with weight loss (≥1.0 kg) at endpoint. The last post-baseline measurement set of both non-missing HbA1c concentration and weight (measured at the same time point, i.e. visit) is used as endpoint value. Patients who do not have a baseline weight measurement, have a protocol violation of baseline HbA1c <=7.0%, and/or have missing post-baseline measurements for HbA1c concentration and/or weight, are included in the analysis as non-responders regarding the primary objective.
Time Frame Baseline, 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.
The full analysis set (FAS) includes all data from all randomised patients receiving at least one dose of the study drug according to the treatment the patients were assigned.

Reporting Groups
  Description
Exenatide Once Weekly Exenatide once weekly : subcutaneous injection, 2mg, once a week
Insulin Detemir Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day

Measured Values
    Exenatide Once Weekly     Insulin Detemir  
Number of Participants Analyzed  
[units: participants]
  111     105  
Percentage of Patients Achieving Glycosylated Hemoglobin (HbA1c) Concentration ≤7.0% With Weight Loss (≥1.0 kg) at Endpoint (Week 26)  
[units: Percentage]
Number ( 95% Confidence Interval )
  44.1  
  ( 34.7 to 53.9 )  
  11.4  
  ( 6.0 to 19.1 )  


Statistical Analysis 1 for Percentage of Patients Achieving Glycosylated Hemoglobin (HbA1c) Concentration ≤7.0% With Weight Loss (≥1.0 kg) at Endpoint (Week 26)
Groups [1] All groups
Method [2] Regression, Logistic
P Value [3] <.0001
Odds Ratio (OR) [4] 6.60
95% Confidence Interval ( 3.17 to 13.73 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Primary objective: to test hypothesis that the percentage of patients with HbA1c ≤7.0% with weight loss (≥1.0 kg) after exenatide QW is superior to insulin detemir.

Sample size estimation: based on the test for difference in percentage between Exenatide QW and insulin detemir. Assuming: common drop-out rate 20%, response rate at endpoint 50% in the exenatide QW group and 25% in the insulin detemir group; 5% significance. 214 patients will provide 90% power to detect a difference.

[2] Other relevant method information, such as adjustments or degrees of freedom:
  Logistic regression model includes treatment group, use of SU (yes/no), baseline HbA1c and baseline weight as main factors.
[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.



2.  Secondary:   Percentage of Patients Who Have Achieved HbA1c ≤7.4% With Weight Loss (≥1.0 kg) at Endpoint (Week 26)   [ Time Frame: Baseline, Week 26 ]

Measure Type Secondary
Measure Title Percentage of Patients Who Have Achieved HbA1c ≤7.4% With Weight Loss (≥1.0 kg) at Endpoint (Week 26)
Measure Description Percentage of patients who have achieved HbA1c ≤7.4% with weight loss (≥1.0 kg) at endpoint (Week 26)
Time Frame Baseline, 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.
The analysis was done for the FAS population (as randomised). For secondary analyses including both final HbA1c concentration and change in weight the last post-baseline measurement set of both non-missing HbA1c and weight was used as endpoint value.

Reporting Groups
  Description
Exenatide Once Weekly Exenatide once weekly : subcutaneous injection, 2mg, once a week
Insulin Detemir Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day

Measured Values
    Exenatide Once Weekly     Insulin Detemir  
Number of Participants Analyzed  
[units: participants]
  107     101  
Percentage of Patients Who Have Achieved HbA1c ≤7.4% With Weight Loss (≥1.0 kg) at Endpoint (Week 26)  
[units: Percentage]
Number ( 95% Confidence Interval )
  58.9  
  ( 49.0 to 68.3 )  
  17.8  
  ( 10.9 to 26.7 )  


Statistical Analysis 1 for Percentage of Patients Who Have Achieved HbA1c ≤7.4% With Weight Loss (≥1.0 kg) at Endpoint (Week 26)
Groups [1] All groups
Method [2] Regression, Logistic
P Value [3] <.0001
Odds Ratio (OR) [4] 7.06
95% Confidence Interval ( 3.64 to 13.70 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Logistic regression model includes the independent variables treatment group, use of SU (yes/no), baseline HbA1c and baseline weight.
[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 HbA1c From Baseline to Week 26   [ Time Frame: Baseline, Week 26 ]

Measure Type Secondary
Measure Title Change in HbA1c From Baseline to Week 26
Measure Description Change in HbA1c from baseline to week 26
Time Frame Baseline, 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.
The analysis was done for the FAS population (as randomised).

Reporting Groups
  Description
Exenatide Once Weekly Exenatide once weekly : subcutaneous injection, 2mg, once a week
Insulin Detemir Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day

Measured Values
    Exenatide Once Weekly     Insulin Detemir  
Number of Participants Analyzed  
[units: participants]
  95     96  
Change in HbA1c From Baseline to Week 26  
[units: Percentage of total hemoglobin]
Least Squares Mean ± Standard Error
  -1.32  ± 0.076     -0.91  ± 0.077  


Statistical Analysis 1 for Change in HbA1c From Baseline to Week 26
Groups [1] All groups
Method [2] Mixed Models Analysis
P Value [3] 0.0001
Least Squares Mean Difference [4] -0.41
Standard Error of the mean ± 0.104
95% Confidence Interval ( -0.62 to -0.20 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Mixed model repeated measures (MMRM) includes baseline value as covariate, study treatment, use of SU (yes/no), week of visit and treatment-by-week interaction as fixed effects and patient and error as random effects.
[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:   Change in Body Weight From Baseline to Week 26   [ Time Frame: Baseline, Week 26 ]

Measure Type Secondary
Measure Title Change in Body Weight From Baseline to Week 26
Measure Description Change in body weight from baseline to week 26
Time Frame Baseline, 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.
The analysis was done for the FAS population (as randomised).

Reporting Groups
  Description
Exenatide Once Weekly Exenatide once weekly : subcutaneous injection, 2mg, once a week
Insulin Detemir Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day

Measured Values
    Exenatide Once Weekly     Insulin Detemir  
Number of Participants Analyzed  
[units: participants]
  96     98  
Change in Body Weight From Baseline to Week 26  
[units: kilograms]
Least Squares Mean ± Standard Error
  -2.79  ± 0.347     0.88  ± 0.351  


Statistical Analysis 1 for Change in Body Weight From Baseline to Week 26
Groups [1] All groups
Method [2] Mixed Models Analysis
P Value [3] <.0001
Least Squares Mean Difference [4] -3.67
Standard Error of the mean ± 0.488
95% Confidence Interval ( -4.63 to -2.71 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Mixed model repeated measures MMRM) includes baseline value as covariate, study treatment, use of SU (yes/no), baseline HbA1c stratum, week of visit and treatment-by-week interaction as fixed effects and patient and error as random effects.
[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.



5.  Secondary:   Percentage of Patients Achieving HbA1c ≤7.4% at Endpoint   [ Time Frame: Week 26 ]

Measure Type Secondary
Measure Title Percentage of Patients Achieving HbA1c ≤7.4% at Endpoint
Measure Description Percentage of patients who have achieved HbA1c ≤.7.4% at endpoint
Time Frame 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.
The analysis was done for the FAS population (as randomised). Patients with baseline HbA1c ≤7.0% and/or no post-baseline HbA1c measurement were regarded as non-responders.

Reporting Groups
  Description
Exenatide Once Weekly Exenatide once weekly : subcutaneous injection, 2mg, once a week
Insulin Detemir Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day

Measured Values
    Exenatide Once Weekly     Insulin Detemir  
Number of Participants Analyzed  
[units: participants]
  111     105  
Percentage of Patients Achieving HbA1c ≤7.4% at Endpoint  
[units: Percentage]
Number ( 95% Confidence Interval )
  66.7  
  ( 57.1 to 75.3 )  
  54.3  
  ( 44.3 to 64.0 )  


Statistical Analysis 1 for Percentage of Patients Achieving HbA1c ≤7.4% at Endpoint
Groups [1] All groups
Method [2] Regression, Logistic
P Value [3] 0.0497
Odds Ratio (OR) [4] 1.79
95% Confidence Interval ( 1.00 to 3.18 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Logistic regression model includes independent variables treatment group, use of SU (yes/no), and baseline HbA1c.
[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.



6.  Secondary:   Percentage of Patients Achieving ≤7.0% at Endpoint   [ Time Frame: Week 26 ]

Measure Type Secondary
Measure Title Percentage of Patients Achieving ≤7.0% at Endpoint
Measure Description Percentage of patients achieving ≤7.0% at endpoint.
Time Frame 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.
The analysis was done for the FAS population (as randomised). Patients with baseline HbA1c ≤7.0% and/or no post-baseline HbA1c measurement were regarded as non-responders.

Reporting Groups
  Description
Exenatide Once Weekly Exenatide once weekly : subcutaneous injection, 2mg, once a week
Insulin Detemir Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day

Measured Values
    Exenatide Once Weekly     Insulin Detemir  
Number of Participants Analyzed  
[units: participants]
  111     105  
Percentage of Patients Achieving ≤7.0% at Endpoint  
[units: Percentage]
Number ( 95% Confidence Interval )
  51.4  
  ( 41.7 to 61.0 )  
  34.3  
  ( 25.3 to 44.2 )  


Statistical Analysis 1 for Percentage of Patients Achieving ≤7.0% at Endpoint
Groups [1] All groups
Method [2] Regression, Logistic
P Value [3] 0.0074
Odds Ratio (OR) [4] 2.21
95% Confidence Interval ( 1.24 to 3.96 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Logistic regression model includes independent variables treatment group, use of SU (yes/no), and baseline HbA1c.
[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.



7.  Secondary:   Percentage of Patients Achieving ≤6.5% at Endpoint   [ Time Frame: Week 26 ]

Measure Type Secondary
Measure Title Percentage of Patients Achieving ≤6.5% at Endpoint
Measure Description Percentage of patients achieving HbA1c ≤6.5% at endpoint
Time Frame 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.
The analysis was done for the FAS population (as randomised). Patients with baseline HbA1c ≤7.0% and/or no post-baseline HbA1c measurement were regarded as non-responders.

Reporting Groups
  Description
Exenatide Once Weekly Exenatide once weekly : subcutaneous injection, 2mg, once a week
Insulin Detemir Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day

Measured Values
    Exenatide Once Weekly     Insulin Detemir  
Number of Participants Analyzed  
[units: participants]
  111     105  
Percentage of Patients Achieving ≤6.5% at Endpoint  
[units: Percentage]
Number ( 95% Confidence Interval )
  27.9  
  ( 19.8 to 37.2 )  
  7.6  
  ( 3.3 to 14.5 )  


Statistical Analysis 1 for Percentage of Patients Achieving ≤6.5% at Endpoint
Groups [1] All groups
Method [2] Regression, Logistic
P Value [3] 0.0002
Odds Ratio (OR) [4] 4.89
95% Confidence Interval ( 2.10 to 11.35 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Logistic regression model includes independent variables treatment group, use of SU (yes/no), and baseline HbA1c.
[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 Fasting Serum Glucose From Baseline to Endpoint (Week 26).   [ Time Frame: Baseline, Week 26 ]

Measure Type Secondary
Measure Title Change in Fasting Serum Glucose From Baseline to Endpoint (Week 26).
Measure Description Change in fasting serum glucose from baseline to endpoint (Week 26).
Time Frame Baseline, 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.

The analysis was done for the FAS population (as randomised).

The last observation carried forward (LOCF) of post baseline values was used for this analysis.


Reporting Groups
  Description
Exenatide Once Weekly Exenatide once weekly : subcutaneous injection, 2mg, once a week
Insulin Detemir Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day

Measured Values
    Exenatide Once Weekly     Insulin Detemir  
Number of Participants Analyzed  
[units: participants]
  108     104  
Change in Fasting Serum Glucose From Baseline to Endpoint (Week 26).  
[units: mmol/L]
Least Squares Mean ± Standard Error
  -2.33  ± 0.191     -2.43  ± 0.196  


Statistical Analysis 1 for Change in Fasting Serum Glucose From Baseline to Endpoint (Week 26).
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.6993
Least Squares Mean Difference [4] 0.10
Standard Error of the mean ± 0.257
95% Confidence Interval ( -0.41 to 0.61 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  ANCOVA model includes treatment group, baseline value, use of SU (yes/no) and baseline HbA1c stratum as factors.
[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:   Changes in Systolic Blood Pressure From Baseline to Week 26   [ Time Frame: Baseline, Week 26 ]

Measure Type Secondary
Measure Title Changes in Systolic Blood Pressure From Baseline to Week 26
Measure Description Change in systolic blood pressure from baseline to Week 26
Time Frame Baseline, 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.
The analysis was done for the FAS population (as randomised).

Reporting Groups
  Description
Exenatide Once Weekly Exenatide once weekly : subcutaneous injection, 2mg, once a week
Insulin Detemir Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day

Measured Values
    Exenatide Once Weekly     Insulin Detemir  
Number of Participants Analyzed  
[units: participants]
  95     98  
Changes in Systolic Blood Pressure From Baseline to Week 26  
[units: mmHg]
Least Squares Mean ± Standard Error
  -7.37  ± 1.342     -2.65  ± 1.339  


Statistical Analysis 1 for Changes in Systolic Blood Pressure From Baseline to Week 26
Groups [1] All groups
Method [2] Mixed Models Analysis
P Value [3] 0.0116
Least Squares Mean Difference [4] -4.72
Standard Error of the mean ± 1.853
95% Confidence Interval ( -8.37 to -1.07 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Mixed model repeated measures (MMRM) includes baseline value as covariate, study treatment, use of SU (yes/no), baseline HbA1c stratum, week of visit and treatment-by-week interaction as fixed effects and patient and error as random effects.
[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.



10.  Secondary:   Change in Diastolic Blood Pressure From Baseline to Week 26.   [ Time Frame: Baseline, Week 26 ]

Measure Type Secondary
Measure Title Change in Diastolic Blood Pressure From Baseline to Week 26.
Measure Description Change in diastolic blood pressure from baseline to week 26.
Time Frame Baseline, 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.
The analysis was done for the FAS population (as randomised).

Reporting Groups
  Description
Exenatide Once Weekly Exenatide once weekly : subcutaneous injection, 2mg, once a week
Insulin Detemir Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day

Measured Values
    Exenatide Once Weekly     Insulin Detemir  
Number of Participants Analyzed  
[units: participants]
  95     98  
Change in Diastolic Blood Pressure From Baseline to Week 26.  
[units: mmHg]
Least Squares Mean ± Standard Error
  -0.79  ± 0.855     -0.34  ± 0.859  


Statistical Analysis 1 for Change in Diastolic Blood Pressure From Baseline to Week 26.
Groups [1] All groups
Method [2] Mixed Models Analysis
P Value [3] 0.7034
Least Squares Mean Difference [4] -0.45
Standard Error of the mean ± 1.179
95% Confidence Interval ( -2.77 to 1.88 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Mixed model repeated measures (MMRM) includes baseline value as covariate, study treatment, use of SU (yes/no), baseline HbA1c stratum, week of visit and treatment-by-week interaction as fixed effects and patient and error as random effects.
[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 Total Cholesterol From Baseline to Endpoint (Week 26).   [ Time Frame: Baseline, Week 26 ]

Measure Type Secondary
Measure Title Change in Total Cholesterol From Baseline to Endpoint (Week 26).
Measure Description Change in total cholesterol from baseline to endpoint (week 26).
Time Frame Baseline, 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.

The analysis was done for the FAS population (as randomised).

The last observation carried forward (LOCF) of post baseline values was used for this analysis.


Reporting Groups
  Description
Exenatide Once Weekly Exenatide once weekly : subcutaneous injection, 2mg, once a week
Insulin Detemir Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day

Measured Values
    Exenatide Once Weekly     Insulin Detemir  
Number of Participants Analyzed  
[units: participants]
  105     100  
Change in Total Cholesterol From Baseline to Endpoint (Week 26).  
[units: mmol/L]
Least Squares Mean ± Standard Error
  -0.09  ± 0.067     0.06  ± 0.068  


Statistical Analysis 1 for Change in Total Cholesterol From Baseline to Endpoint (Week 26).
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.1061
Least Squares Mean Difference [4] -0.15
Standard Error of the mean ± 0.090
95% Confidence Interval ( -0.32 to 0.03 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  ANCOVA model includes treatment group, baseline value, use of SU (yes/no) and baseline HbA1c stratum as factors.
[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 High-density Lipoprotein (HDL) Cholesterol From Baseline to Endpoint (Week 26).   [ Time Frame: Baseline, Week 26 ]

Measure Type Secondary
Measure Title Change in High-density Lipoprotein (HDL) Cholesterol From Baseline to Endpoint (Week 26).
Measure Description Change in High-density lipoprotein (HDL) cholesterol from baseline to endpoint (week 26).
Time Frame Baseline, 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.
The analysis was done for the FAS population (as randomised). The last observation carried forward (LOCF) of post baseline values was used for this analysis.

Reporting Groups
  Description
Exenatide Once Weekly Exenatide once weekly : subcutaneous injection, 2mg, once a week
Insulin Detemir Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day

Measured Values
    Exenatide Once Weekly     Insulin Detemir  
Number of Participants Analyzed  
[units: participants]
  105     100  
Change in High-density Lipoprotein (HDL) Cholesterol From Baseline to Endpoint (Week 26).  
[units: mmol/L]
Least Squares Mean ± Standard Error
  0.02  ± 0.014     0.04  ± 0.015  


Statistical Analysis 1 for Change in High-density Lipoprotein (HDL) Cholesterol From Baseline to Endpoint (Week 26).
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.4638
Least Squares Mean Difference [4] -0.01
Standard Error of the mean ± 0.020
95% Confidence Interval ( -0.05 to 0.02 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  ANCOVA model includes treatment group, baseline value, use of SU (yes/no) and baseline HbA1c stratum as factors.
[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.



13.  Secondary:   Change in Triglycerides From Baseline to Endpoint (Week 26).   [ Time Frame: Baseline, Week 26 ]

Measure Type Secondary
Measure Title Change in Triglycerides From Baseline to Endpoint (Week 26).
Measure Description Change in triglycerides from baseline to endpoint (week 26).
Time Frame Baseline, 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.
The analysis was done for the FAS population (as randomised). The last observation carried forward (LOCF) of post baseline values was used for this analysis.

Reporting Groups
  Description
Exenatide Once Weekly Exenatide once weekly : subcutaneous injection, 2mg, once a week
Insulin Detemir Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day

Measured Values
    Exenatide Once Weekly     Insulin Detemir  
Number of Participants Analyzed  
[units: participants]
  105     100  
Change in Triglycerides From Baseline to Endpoint (Week 26).  
[units: mmol/L]
Least Squares Mean ± Standard Error
  -0.01  ± 0.079     -0.08  ± 0.081  


Statistical Analysis 1 for Change in Triglycerides From Baseline to Endpoint (Week 26).
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.4967
Least Squares Mean Difference [4] 0.07
Standard Error of the mean ± 0.107
95% Confidence Interval ( -0.14 to 0.28 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  ANCOVA model includes treatment group, baseline value, use of SU (yes/no) and baseline HbA1c stratum as factors.
[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.



14.  Secondary:   Hypoglycemia Rate Per Year   [ Time Frame: Baseline, Week 26 ]

Measure Type Secondary
Measure Title Hypoglycemia Rate Per Year
Measure Description All confirmed hypoglycemia episodes defined as either minor (any time a patient feels that he or she is experiencing a sign or symptom associated with hypoglycaemia and blood glucose (BG) <3.0 mmol/L (54 mg/dL)) or major (any hypoglycaemic episode with symptoms consistent with hypoglycaemia, resulting in loss of consciousness or seizure, and shows prompt recovery in response to administration of glucagon or glucose, or BG measurement < 3.0mmol/L is available and the patient is not capable of self-treating were taken into account.
Time Frame Baseline, Week 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.
Full analysis set (as randomized).

Reporting Groups
  Description
Exenatide Once Weekly Exenatide once weekly : subcutaneous injection, 2mg, once a week
Insulin Detemir Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day

Measured Values
    Exenatide Once Weekly     Insulin Detemir  
Number of Participants Analyzed  
[units: participants]
  111     105  
Hypoglycemia Rate Per Year  
[units: events per subject-year]
Number ( 95% Confidence Interval )
  0.06  
  ( 0.02 to 0.20 )  
  0.10  
  ( 0.03 to 0.30 )  


Statistical Analysis 1 for Hypoglycemia Rate Per Year
Groups [1] All groups
Method [2] Poisson regression
P Value [3] 0.3247
Ratio [4] 0.58
Standard Error of the mean ± 0.322
95% Confidence Interval ( 0.19 to 1.72 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The number of episodes by patient were compared between treatment groups using a poisson model with effects for treatment and baseline HbA1c and the logarithm of the days of exposure as the offset variable.
[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.




  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 NOT 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.


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: Chief Medical Officer
Organization: Eli Lilly and Company
phone: 1-877-285-4559
e-mail: clinicaltrials@amylin.com


No publications provided


Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01003184     History of Changes
Other Study ID Numbers: H8O-EW-GWDL
Study First Received: October 15, 2009
Results First Received: November 20, 2012
Last Updated: September 18, 2013
Health Authority: Ireland: Irish Medicines Board
United Kingdom: Medicines and Healthcare Products Regulatory Agency