Trial Outcomes & Findings for Safety and Efficacy of Exenatide Once Weekly Versus Liraglutide in Subjects With Type 2 Diabetes (NCT NCT01029886)
NCT ID: NCT01029886
Last Updated: 2015-04-09
Results Overview
Change in HbA1c from baseline to the treatment endpoint at Week 26.
COMPLETED
PHASE3
912 participants
Baseline, Week 26
2015-04-09
Participant Flow
Participant milestones
| Measure |
Exenatide Once Weekly
Subcutaneous injection, 2mg, once weekly
|
Liraglutide Once Daily
Subcutaneous injection, forced titration to 1.8mg, once daily
|
|---|---|---|
|
Overall Study
STARTED
|
461
|
451
|
|
Overall Study
Intent to Treat (ITT)
|
461
|
450
|
|
Overall Study
COMPLETED
|
400
|
391
|
|
Overall Study
NOT COMPLETED
|
61
|
60
|
Reasons for withdrawal
| Measure |
Exenatide Once Weekly
Subcutaneous injection, 2mg, once weekly
|
Liraglutide Once Daily
Subcutaneous injection, forced titration to 1.8mg, once daily
|
|---|---|---|
|
Overall Study
Adverse Event
|
12
|
25
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
Physician Decision
|
2
|
6
|
|
Overall Study
Protocol Violation
|
17
|
5
|
|
Overall Study
Withdrawal by Subject
|
8
|
18
|
|
Overall Study
Entry Criteria Not Met
|
13
|
5
|
|
Overall Study
Sponsor Decision
|
1
|
0
|
|
Overall Study
Loss Glucose Control
|
7
|
1
|
Baseline Characteristics
Safety and Efficacy of Exenatide Once Weekly Versus Liraglutide in Subjects With Type 2 Diabetes
Baseline characteristics by cohort
| Measure |
Exenatide Once Weekly
n=461 Participants
Subcutaneous injection, 2mg, once weekly
|
Liraglutide Once Daily
n=450 Participants
Subcutaneous injection, forced titration to 1.8mg, once daily
|
Total
n=911 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
386 Participants
n=5 Participants
|
360 Participants
n=7 Participants
|
746 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
75 Participants
n=5 Participants
|
90 Participants
n=7 Participants
|
165 Participants
n=5 Participants
|
|
Age, Continuous
|
56.6 years
STANDARD_DEVIATION 9.43 • n=5 Participants
|
56.7 years
STANDARD_DEVIATION 9.59 • n=7 Participants
|
56.6 years
STANDARD_DEVIATION 9.51 • n=5 Participants
|
|
Sex: Female, Male
Female
|
207 Participants
n=5 Participants
|
205 Participants
n=7 Participants
|
412 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
254 Participants
n=5 Participants
|
245 Participants
n=7 Participants
|
499 Participants
n=5 Participants
|
|
Glycosylated hemoglobin (HbA1c)
|
8.45 percentage of total hemoglobin
STANDARD_DEVIATION 1.014 • n=5 Participants
|
8.43 percentage of total hemoglobin
STANDARD_DEVIATION 0.996 • n=7 Participants
|
8.44 percentage of total hemoglobin
STANDARD_DEVIATION 1.004 • n=5 Participants
|
|
Weight
|
90.88 kg
STANDARD_DEVIATION 19.472 • n=5 Participants
|
91.13 kg
STANDARD_DEVIATION 19.118 • n=7 Participants
|
91.00 kg
STANDARD_DEVIATION 19.288 • n=5 Participants
|
|
Background Oral Antidiabetic Agent (OAD)
Metformin (MET)
|
150 participants
n=5 Participants
|
136 participants
n=7 Participants
|
286 participants
n=5 Participants
|
|
Background Oral Antidiabetic Agent (OAD)
Sulfonylurea (SU)
|
18 participants
n=5 Participants
|
18 participants
n=7 Participants
|
36 participants
n=5 Participants
|
|
Background Oral Antidiabetic Agent (OAD)
Pioglitazone (PIO)
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Background Oral Antidiabetic Agent (OAD)
MET+SU
|
275 participants
n=5 Participants
|
277 participants
n=7 Participants
|
552 participants
n=5 Participants
|
|
Background Oral Antidiabetic Agent (OAD)
MET+SU+PIO
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Background Oral Antidiabetic Agent (OAD)
MET+PIO
|
16 participants
n=5 Participants
|
18 participants
n=7 Participants
|
34 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 26Population: ITT Population: all patients who were randomized and received study drug. All observed data from all scheduled visits (including early termination visits) were included in the mixed-model repeated measures (MMRM) analysis. Data collected at the early termination visits were mapped into the following scheduled visits.
Change in HbA1c from baseline to the treatment endpoint at Week 26.
Outcome measures
| Measure |
Exenatide Once Weekly
n=390 Participants
Subcutaneous injection, 2mg, once weekly
|
Liraglutide Once Daily
n=386 Participants
Subcutaneous injection, forced titration to 1.8mg, once daily
|
Exenatide Once Weekly Without SU Use at Screening
Subcutaneous injection, 2mg, once weekly and without SU use at screening
|
Liraglutide Once Daily Without SU Use at Screening
Subcutaneous injection, forced titration to 1.8mg, once daily and without SU use at screening
|
|---|---|---|---|---|
|
Change in HbA1c From Baseline to Week 26
|
-1.28 percentage of total hemoglobin
Standard Error 0.05
|
-1.48 percentage of total hemoglobin
Standard Error 0.05
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: ITT Population. Missing data at endpoint was imputed using last observation carried forward approach.
Percentage of patients achieving HbA1c \<7.0% at treatment endpoint at Week 26.
Outcome measures
| Measure |
Exenatide Once Weekly
n=461 Participants
Subcutaneous injection, 2mg, once weekly
|
Liraglutide Once Daily
n=450 Participants
Subcutaneous injection, forced titration to 1.8mg, once daily
|
Exenatide Once Weekly Without SU Use at Screening
Subcutaneous injection, 2mg, once weekly and without SU use at screening
|
Liraglutide Once Daily Without SU Use at Screening
Subcutaneous injection, forced titration to 1.8mg, once daily and without SU use at screening
|
|---|---|---|---|---|
|
Percentage of Patients Achieving HbA1c <7.0% at Week 26
|
52.7 percentage of patients
|
60.2 percentage of patients
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: 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.
Change in fasting serum glucose from baseline to the treatment endpoint at Week 26.
Outcome measures
| Measure |
Exenatide Once Weekly
n=403 Participants
Subcutaneous injection, 2mg, once weekly
|
Liraglutide Once Daily
n=385 Participants
Subcutaneous injection, forced titration to 1.8mg, once daily
|
Exenatide Once Weekly Without SU Use at Screening
Subcutaneous injection, 2mg, once weekly and without SU use at screening
|
Liraglutide Once Daily Without SU Use at Screening
Subcutaneous injection, forced titration to 1.8mg, once daily and without SU use at screening
|
|---|---|---|---|---|
|
Change in Fasting Serum Glucose From Baseline to Week 26
|
-1.76 mmol/L
Standard Error 0.11
|
-2.12 mmol/L
Standard Error 0.12
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: 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.
Change in body weight from baseline to the treatment endpoint at Week 26.
Outcome measures
| Measure |
Exenatide Once Weekly
n=404 Participants
Subcutaneous injection, 2mg, once weekly
|
Liraglutide Once Daily
n=398 Participants
Subcutaneous injection, forced titration to 1.8mg, once daily
|
Exenatide Once Weekly Without SU Use at Screening
Subcutaneous injection, 2mg, once weekly and without SU use at screening
|
Liraglutide Once Daily Without SU Use at Screening
Subcutaneous injection, forced titration to 1.8mg, once daily and without SU use at screening
|
|---|---|---|---|---|
|
Change in Body Weight From Baseline to Week 26
|
-2.68 kg
Standard Error 0.18
|
-3.57 kg
Standard Error 0.18
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: 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.
Change in total cholesterol from baseline to the treatment endpoint at Week 26.
Outcome measures
| Measure |
Exenatide Once Weekly
n=402 Participants
Subcutaneous injection, 2mg, once weekly
|
Liraglutide Once Daily
n=386 Participants
Subcutaneous injection, forced titration to 1.8mg, once daily
|
Exenatide Once Weekly Without SU Use at Screening
Subcutaneous injection, 2mg, once weekly and without SU use at screening
|
Liraglutide Once Daily Without SU Use at Screening
Subcutaneous injection, forced titration to 1.8mg, once daily and without SU use at screening
|
|---|---|---|---|---|
|
Change in Total Cholesterol From Baseline to Week 26
|
-0.06 mmol/L
Standard Error 0.04
|
-0.15 mmol/L
Standard Error 0.04
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: 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.
Change in HDL-C from baseline to the treatment endpoint at Week 26.
Outcome measures
| Measure |
Exenatide Once Weekly
n=402 Participants
Subcutaneous injection, 2mg, once weekly
|
Liraglutide Once Daily
n=386 Participants
Subcutaneous injection, forced titration to 1.8mg, once daily
|
Exenatide Once Weekly Without SU Use at Screening
Subcutaneous injection, 2mg, once weekly and without SU use at screening
|
Liraglutide Once Daily Without SU Use at Screening
Subcutaneous injection, forced titration to 1.8mg, once daily and without SU use at screening
|
|---|---|---|---|---|
|
Change in High-Density Lipoprotein Cholesterol (HDL-C) From Baseline to Week 26
|
0.02 mmol/L
Standard Error 0.01
|
0.02 mmol/L
Standard Error 0.01
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: 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.
Ratio of fasting triglycerides (measured in mmol/L) treatment endpoint at Week 26 to baseline. Log(Postbaseline fasting triglycerides) - log(Baseline fasting triglycerides); change from baseline to the treatment endpoint at Week 26 is presented as ratio of Week 26 to baseline.
Outcome measures
| Measure |
Exenatide Once Weekly
n=395 Participants
Subcutaneous injection, 2mg, once weekly
|
Liraglutide Once Daily
n=385 Participants
Subcutaneous injection, forced titration to 1.8mg, once daily
|
Exenatide Once Weekly Without SU Use at Screening
Subcutaneous injection, 2mg, once weekly and without SU use at screening
|
Liraglutide Once Daily Without SU Use at Screening
Subcutaneous injection, forced titration to 1.8mg, once daily and without SU use at screening
|
|---|---|---|---|---|
|
Ratio of Fasting Triglycerides at Week 26 to Baseline
|
0.97 ratio
Standard Error 0.02
|
0.89 ratio
Standard Error 0.02
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: 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.
Change in SBP from baseline to the treatment endpoint at Week 26.
Outcome measures
| Measure |
Exenatide Once Weekly
n=404 Participants
Subcutaneous injection, 2mg, once weekly
|
Liraglutide Once Daily
n=398 Participants
Subcutaneous injection, forced titration to 1.8mg, once daily
|
Exenatide Once Weekly Without SU Use at Screening
Subcutaneous injection, 2mg, once weekly and without SU use at screening
|
Liraglutide Once Daily Without SU Use at Screening
Subcutaneous injection, forced titration to 1.8mg, once daily and without SU use at screening
|
|---|---|---|---|---|
|
Change in Systolic Blood Pressure (SBP) From Baseline to Week 26
|
-2.48 mmHg
Standard Error 0.56
|
-3.45 mmHg
Standard Error 0.57
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: 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.
Change in DBP from baseline to the treatment endpoint at Week 26.
Outcome measures
| Measure |
Exenatide Once Weekly
n=404 Participants
Subcutaneous injection, 2mg, once weekly
|
Liraglutide Once Daily
n=398 Participants
Subcutaneous injection, forced titration to 1.8mg, once daily
|
Exenatide Once Weekly Without SU Use at Screening
Subcutaneous injection, 2mg, once weekly and without SU use at screening
|
Liraglutide Once Daily Without SU Use at Screening
Subcutaneous injection, forced titration to 1.8mg, once daily and without SU use at screening
|
|---|---|---|---|---|
|
Change in Diastolic Blood Pressure (DBP) From Baseline to Week 26
|
-0.49 mmHg
Standard Error 0.37
|
-0.51 mmHg
Standard Error 0.37
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline to Week 26Population: ITT Population.
Major hypoglycemia: any episode with symptoms consistent with hypoglycemia that resulted in loss of consciousness or seizure with prompt recovery in response to administration of glucagon or glucose OR documented hypoglycemia (blood glucose \<3.0 mmol/L \[54 mg/dL\]) and required the assistance of another person. Minor hypoglycemia: any sign or symptom associated with hypoglycemia that is either self-treated by the patient or resolves on its own AND has a concurrent finger stick blood glucose \<3.0 mmol/L (54 mg/dL) and not classified as major hypoglycemia. Event rate per subject year was calculated for each subject: (number of events observed from a subject/exposure from a subject)\*365.25 where exposure = last post-baseline visit date - baseline visit date. Mean and Standard Error were then derived from ITT.
Outcome measures
| Measure |
Exenatide Once Weekly
n=294 Participants
Subcutaneous injection, 2mg, once weekly
|
Liraglutide Once Daily
n=296 Participants
Subcutaneous injection, forced titration to 1.8mg, once daily
|
Exenatide Once Weekly Without SU Use at Screening
n=167 Participants
Subcutaneous injection, 2mg, once weekly and without SU use at screening
|
Liraglutide Once Daily Without SU Use at Screening
n=154 Participants
Subcutaneous injection, forced titration to 1.8mg, once daily and without SU use at screening
|
|---|---|---|---|---|
|
Assessment of Event Rate of Treatment-emergent Hypoglycemic Events
Major Hypoglycemia
|
0.00 events per subject-year
Standard Error 0.000
|
0.00 events per subject-year
Standard Error 0.000
|
0.00 events per subject-year
Standard Error 0.000
|
0.00 events per subject-year
Standard Error 0.000
|
|
Assessment of Event Rate of Treatment-emergent Hypoglycemic Events
Minor Hypoglycemia
|
0.76 events per subject-year
Standard Error 0.143
|
0.55 events per subject-year
Standard Error 0.126
|
0.67 events per subject-year
Standard Error 0.417
|
0.05 events per subject-year
Standard Error 0.026
|
Adverse Events
Exenatide Once Weekly
Liraglutide Once Daily
Serious adverse events
| Measure |
Exenatide Once Weekly
n=461 participants at risk
Subcutaneous injection, 2mg, once weekly
|
Liraglutide Once Daily
n=450 participants at risk
Subcutaneous injection, forced titration to 1.8mg, once daily
|
|---|---|---|
|
Infections and infestations
Appendicitis
|
0.43%
2/461
|
0.00%
0/450
|
|
Nervous system disorders
Cerebrovascular accident
|
0.22%
1/461
|
0.22%
1/450
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.22%
1/461
|
0.00%
0/450
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.22%
1/461
|
0.00%
0/450
|
|
Cardiac disorders
Coronary artery disease
|
0.22%
1/461
|
0.22%
1/450
|
|
Psychiatric disorders
Depression
|
0.22%
1/461
|
0.00%
0/450
|
|
Gastrointestinal disorders
Gastrointestinal disorder
|
0.22%
1/461
|
0.00%
0/450
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.22%
1/461
|
0.00%
0/450
|
|
Ear and labyrinth disorders
Hearing impaired
|
0.22%
1/461
|
0.00%
0/450
|
|
General disorders
Impaired healing
|
0.22%
1/461
|
0.00%
0/450
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.22%
1/461
|
0.00%
0/450
|
|
Injury, poisoning and procedural complications
Joint dislocation
|
0.22%
1/461
|
0.00%
0/450
|
|
Cardiac disorders
Myocardial infarction
|
0.22%
1/461
|
0.00%
0/450
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.22%
1/461
|
0.00%
0/450
|
|
Injury, poisoning and procedural complications
Patella fracture
|
0.22%
1/461
|
0.00%
0/450
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.22%
1/461
|
0.00%
0/450
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Spinal cord neoplasm
|
0.22%
1/461
|
0.00%
0/450
|
|
Immune system disorders
Anaphylactic reaction
|
0.00%
0/461
|
0.22%
1/450
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/461
|
0.22%
1/450
|
|
Nervous system disorders
Brain stem infarction
|
0.00%
0/461
|
0.22%
1/450
|
|
General disorders
Chest pain
|
0.00%
0/461
|
0.22%
1/450
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/461
|
0.22%
1/450
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/461
|
0.22%
1/450
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/461
|
0.22%
1/450
|
Other adverse events
| Measure |
Exenatide Once Weekly
n=461 participants at risk
Subcutaneous injection, 2mg, once weekly
|
Liraglutide Once Daily
n=450 participants at risk
Subcutaneous injection, forced titration to 1.8mg, once daily
|
|---|---|---|
|
General disorders
Injection site nodule
|
10.4%
48/461
|
1.1%
5/450
|
|
Gastrointestinal disorders
Nausea
|
9.3%
43/461
|
20.7%
93/450
|
|
Infections and infestations
Nasopharyngitis
|
6.7%
31/461
|
7.1%
32/450
|
|
Gastrointestinal disorders
Diarrhoea
|
6.1%
28/461
|
12.9%
58/450
|
|
Nervous system disorders
Headache
|
5.9%
27/461
|
8.4%
38/450
|
|
Metabolism and nutrition disorders
Decreased appetite
|
3.7%
17/461
|
6.4%
29/450
|
|
Gastrointestinal disorders
Vomiting
|
3.7%
17/461
|
10.4%
47/450
|
|
Gastrointestinal disorders
Dyspepsia
|
2.4%
11/461
|
6.0%
27/450
|
|
General disorders
Therapeutic response unexpected
|
2.4%
11/461
|
6.0%
27/450
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60