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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
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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
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
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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
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
  Show All Outcome Measures

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

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

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

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 ]

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 ]

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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


  Serious Adverse Events


  Other Adverse Events
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Time Frame The adverse events were collected in a time span of 78 weeks.
Additional Description The safety analysis set included all subjects who had been exposed to at least one dose of the study products.

Frequency Threshold
Threshold above which other adverse events are reported   5%  

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)

Other Adverse Events
    Liraglutide -> Liraglutide -> Liraglutide     Exenatide -> Liraglutide -> Liraglutide  
Total, other (not including serious) adverse events      
# participants affected / at risk     162/235     167/232  
Gastrointestinal disorders      
Constipation † 1    
# participants affected / at risk     18/235 (7.66%)     10/232 (4.31%)  
# events     18     13  
Diarrhoea † 1    
# participants affected / at risk     35/235 (14.89%)     37/232 (15.95%)  
# events     47     50  
Dyspepsia † 1    
# participants affected / at risk     25/235 (10.64%)     14/232 (6.03%)  
# events     35     17  
Nausea † 1    
# participants affected / at risk     64/235 (27.23%)     68/232 (29.31%)  
# events     87     92  
Vomiting † 1    
# participants affected / at risk     19/235 (8.09%)     26/232 (11.21%)  
# events     20     31  
Infections and infestations      
Bronchitis † 1    
# participants affected / at risk     15/235 (6.38%)     20/232 (8.62%)  
# events     18     22  
Influenza † 1    
# participants affected / at risk     13/235 (5.53%)     11/232 (4.74%)  
# events     14     11  
Nasopharyngitis † 1    
# participants affected / at risk     43/235 (18.30%)     42/232 (18.10%)  
# events     59     71  
Sinusitis † 1    
# participants affected / at risk     12/235 (5.11%)     9/232 (3.88%)  
# events     14     13  
Upper respiratory tract infection † 1    
# participants affected / at risk     26/235 (11.06%)     28/232 (12.07%)  
# events     33     30  
Metabolism and nutrition disorders      
Anorexia † 1    
# participants affected / at risk     10/235 (4.26%)     12/232 (5.17%)  
# events     10     12  
Musculoskeletal and connective tissue disorders      
Back pain † 1    
# participants affected / at risk     22/235 (9.36%)     12/232 (5.17%)  
# events     30     13  
Nervous system disorders      
Dizziness † 1    
# participants affected / at risk     14/235 (5.96%)     9/232 (3.88%)  
# events     16     9  
Headache † 1    
# participants affected / at risk     29/235 (12.34%)     28/232 (12.07%)  
# events     38     40  
Vascular disorders      
Hypertension † 1    
# participants affected / at risk     10/235 (4.26%)     12/232 (5.17%)  
# events     10     12  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA (12.0)



  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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