Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

Safety and Efficacy of Exenatide Once Weekly Versus Liraglutide in Subjects With Type 2 Diabetes

This study has been completed.
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01029886
First received: December 8, 2009
Last updated: March 20, 2015
Last verified: March 2015
Results First Received: February 14, 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: liraglutide

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups
  Description
Exenatide Once Weekly Subcutaneous injection, 2mg, once weekly
Liraglutide Once Daily Subcutaneous injection, forced titration to 1.8mg, once daily

Participant Flow:   Overall Study
    Exenatide Once Weekly   Liraglutide Once Daily
STARTED   461   451 
Intent to Treat (ITT)   461   450 
COMPLETED   400   391 
NOT COMPLETED   61   60 
Adverse Event                12                25 
Lost to Follow-up                1                0 
Physician Decision                2                6 
Protocol Violation                17                5 
Withdrawal by Subject                8                18 
Entry Criteria Not Met                13                5 
Sponsor Decision                1                0 
Loss Glucose Control                7                1 



  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.
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Reporting Groups
  Description
Exenatide Once Weekly Subcutaneous injection, 2mg, once weekly
Liraglutide Once Daily Subcutaneous injection, forced titration to 1.8mg, once daily
Total Total of all reporting groups

Baseline Measures
   Exenatide Once Weekly   Liraglutide Once Daily   Total 
Overall Participants Analyzed 
[Units: Participants]
 461   450   911 
Age 
[Units: Participants]
     
<=18 years   0   0   0 
Between 18 and 65 years   386   360   746 
>=65 years   75   90   165 
Age 
[Units: Years]
Mean (Standard Deviation)
 56.6  (9.43)   56.7  (9.59)   56.6  (9.51) 
Gender 
[Units: Participants]
     
Female   207   205   412 
Male   254   245   499 
Glycosylated hemoglobin (HbA1c) 
[Units: Percentage of total hemoglobin]
Mean (Standard Deviation)
 8.45  (1.014)   8.43  (0.996)   8.44  (1.004) 
Weight 
[Units: Kg]
Mean (Standard Deviation)
 90.88  (19.472)   91.13  (19.118)   91.00  (19.288) 
Background Oral Antidiabetic Agent (OAD) 
[Units: Participants]
     
Metformin (MET)   150   136   286 
Sulfonylurea (SU)   18   18   36 
Pioglitazone (PIO)   1   0   1 
MET+SU   275   277   552 
MET+PIO   16   18   34 
MET+SU+PIO   1   1   2 


  Outcome Measures
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1.  Primary:   Change in HbA1c From Baseline to Week 26   [ Time Frame: Baseline, Week 26 ]

2.  Secondary:   Percentage of Patients Achieving HbA1c <7.0% at Week 26   [ Time Frame: Baseline, Week 26 ]

3.  Secondary:   Change in Fasting Serum Glucose From Baseline to Week 26   [ Time Frame: Baseline, Week 26 ]

4.  Secondary:   Change in Body Weight From Baseline to Week 26   [ Time Frame: Baseline, Week 26 ]
  Hide Outcome Measure 4

Measure Type Secondary
Measure Title Change in Body Weight From Baseline to Week 26
Measure Description Change in body weight from baseline to the treatment endpoint at 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.
ITT Population. All observed data from all scheduled visits (including early termination visits) were included in the MMRM analysis. Data collected at the early termination visits were mapped into the following scheduled visits.

Reporting Groups
  Description
Exenatide Once Weekly Subcutaneous injection, 2mg, once weekly
Liraglutide Once Daily Subcutaneous injection, forced titration to 1.8mg, once daily

Measured Values
   Exenatide Once Weekly   Liraglutide Once Daily 
Participants Analyzed 
[Units: Participants]
 404   398 
Change in Body Weight From Baseline to Week 26 
[Units: Kg]
Least Squares Mean (Standard Error)
 -2.68  (0.18)   -3.57  (0.18) 


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] <.001
Least Squares Mean Difference [4] 0.90
Standard Error of the mean (0.26)
95% Confidence Interval 0.39 to 1.40
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  MMRM model includes treatment, baseline body weight, HbA1c stratum, country, background OAD, week of visit, and treatment-by-week interaction as fixed effects and subject and error as random effects.
[2] Other relevant method information, such as adjustments or degrees of freedom:
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[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:
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5.  Secondary:   Change in Total Cholesterol From Baseline to Week 26   [ Time Frame: Baseline, Week 26 ]

6.  Secondary:   Change in High-Density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26   [ Time Frame: Baseline, Week 26 ]

7.  Secondary:   Ratio of Fasting Triglycerides at Week 26 to Baseline   [ Time Frame: Baseline, Week 26 ]

8.  Secondary:   Change in Systolic Blood Pressure (SBP) From Baseline to Week 26   [ Time Frame: Baseline, Week 26 ]

9.  Secondary:   Change in Diastolic Blood Pressure (DBP) From Baseline to Week 26   [ Time Frame: Baseline, Week 26 ]

10.  Secondary:   Assessment of Event Rate of Treatment-emergent Hypoglycemic Events   [ Time Frame: Baseline to Week 26 ]


  Serious Adverse Events
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Time Frame No text entered.
Additional Description No text entered.

Reporting Groups
  Description
Exenatide Once Weekly Subcutaneous injection, 2mg, once weekly
Liraglutide Once Daily Subcutaneous injection, forced titration to 1.8mg, once daily

Serious Adverse Events
    Exenatide Once Weekly   Liraglutide Once Daily
Total, serious adverse events     
# participants affected / at risk   13/461 (2.82%)   7/450 (1.56%) 
Cardiac disorders     
Coronary artery disease * 1     
# participants affected / at risk   1/461 (0.22%)   1/450 (0.22%) 
Myocardial infarction * 1     
# participants affected / at risk   1/461 (0.22%)   0/450 (0.00%) 
Atrial fibrillation * 1     
# participants affected / at risk   0/461 (0.00%)   1/450 (0.22%) 
Ear and labyrinth disorders     
Hearing impaired * 1     
# participants affected / at risk   1/461 (0.22%)   0/450 (0.00%) 
Gastrointestinal disorders     
Gastrointestinal disorder * 1     
# participants affected / at risk   1/461 (0.22%)   0/450 (0.00%) 
Gastrointestinal haemorrhage * 1     
# participants affected / at risk   1/461 (0.22%)   0/450 (0.00%) 
Pancreatitis acute * 1     
# participants affected / at risk   1/461 (0.22%)   0/450 (0.00%) 
Constipation * 1     
# participants affected / at risk   0/461 (0.00%)   1/450 (0.22%) 
Diarrhoea * 1     
# participants affected / at risk   0/461 (0.00%)   1/450 (0.22%) 
Vomiting * 1     
# participants affected / at risk   0/461 (0.00%)   1/450 (0.22%) 
General disorders     
Impaired healing * 1     
# participants affected / at risk   1/461 (0.22%)   0/450 (0.00%) 
Chest pain * 1     
# participants affected / at risk   0/461 (0.00%)   1/450 (0.22%) 
Hepatobiliary disorders     
Cholecystitis acute * 1     
# participants affected / at risk   1/461 (0.22%)   0/450 (0.00%) 
Cholelithiasis * 1     
# participants affected / at risk   1/461 (0.22%)   0/450 (0.00%) 
Immune system disorders     
Anaphylactic reaction * 1     
# participants affected / at risk   0/461 (0.00%)   1/450 (0.22%) 
Infections and infestations     
Appendicitis * 1     
# participants affected / at risk   2/461 (0.43%)   0/450 (0.00%) 
Injury, poisoning and procedural complications     
Joint dislocation * 1     
# participants affected / at risk   1/461 (0.22%)   0/450 (0.00%) 
Patella fracture * 1     
# participants affected / at risk   1/461 (0.22%)   0/450 (0.00%) 
Musculoskeletal and connective tissue disorders     
Intervertebral disc protrusion * 1     
# participants affected / at risk   1/461 (0.22%)   0/450 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Prostate cancer * 1     
# participants affected / at risk   1/461 (0.22%)   0/450 (0.00%) 
Spinal cord neoplasm * 1     
# participants affected / at risk   1/461 (0.22%)   0/450 (0.00%) 
Nervous system disorders     
Cerebrovascular accident * 1     
# participants affected / at risk   1/461 (0.22%)   1/450 (0.22%) 
Brain stem infarction * 1     
# participants affected / at risk   0/461 (0.00%)   1/450 (0.22%) 
Psychiatric disorders     
Depression * 1     
# participants affected / at risk   1/461 (0.22%)   0/450 (0.00%) 
* Events were collected by non-systematic assessment
1 Term from vocabulary, MedDRA 14.0




  Other Adverse Events


  Limitations and Caveats
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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
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  More Information