Trial Outcomes & Findings for Efficacy of Once-Weekly Exenatide Versus Once or Twice Daily Insulin Detemir in Patients With Type 2 Diabetes (NCT NCT01003184)
NCT ID: NCT01003184
Last Updated: 2015-04-07
Results Overview
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.
COMPLETED
PHASE3
222 participants
Baseline, Week 26
2015-04-07
Participant Flow
6 patients who were enrolled and randomized, subsequently discontinued the study before receiving study drug. These patients were not included in analysis.
Participant milestones
| Measure |
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
|
|---|---|---|
|
Overall Study
STARTED
|
111
|
111
|
|
Overall Study
Full Analysis Set (FAS)
|
111
|
105
|
|
Overall Study
COMPLETED
|
92
|
99
|
|
Overall Study
NOT COMPLETED
|
19
|
12
|
Reasons for withdrawal
| Measure |
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
|
|---|---|---|
|
Overall Study
Adverse Event
|
12
|
5
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
Loss of glucose control
|
1
|
1
|
|
Overall Study
Protocol Violation
|
3
|
0
|
|
Overall Study
Withdrawal by Subject
|
1
|
6
|
|
Overall Study
Physician Decision
|
1
|
0
|
Baseline Characteristics
Efficacy of Once-Weekly Exenatide Versus Once or Twice Daily Insulin Detemir in Patients With Type 2 Diabetes
Baseline characteristics by cohort
| Measure |
Exenatide Once Weekly
n=111 Participants
Exenatide once weekly : subcutaneous injection, 2mg, once a week
|
Insulin Detemir
n=105 Participants
Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day
|
Total
n=216 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
|
74 Participants
n=5 Participants
|
78 Participants
n=7 Participants
|
152 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
37 Participants
n=5 Participants
|
27 Participants
n=7 Participants
|
64 Participants
n=5 Participants
|
|
Age, Continuous
|
59.2 years
STANDARD_DEVIATION 9.86 • n=5 Participants
|
57.8 years
STANDARD_DEVIATION 9.48 • n=7 Participants
|
58.5 years
STANDARD_DEVIATION 9.68 • n=5 Participants
|
|
Sex: Female, Male
Female
|
40 Participants
n=5 Participants
|
33 Participants
n=7 Participants
|
73 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
71 Participants
n=5 Participants
|
72 Participants
n=7 Participants
|
143 Participants
n=5 Participants
|
|
HbA1c
|
8.4 Percentage of total hemoglobin
STANDARD_DEVIATION 0.85 • n=5 Participants
|
8.4 Percentage of total hemoglobin
STANDARD_DEVIATION 0.88 • n=7 Participants
|
8.4 Percentage of total hemoglobin
STANDARD_DEVIATION 0.86 • n=5 Participants
|
|
Weight
|
96.7 Kilograms
STANDARD_DEVIATION 17.03 • n=5 Participants
|
97.9 Kilograms
STANDARD_DEVIATION 15.82 • n=7 Participants
|
97.3 Kilograms
STANDARD_DEVIATION 16.42 • n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 26Population: 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.
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.
Outcome measures
| Measure |
Exenatide Once Weekly
n=111 Participants
Exenatide once weekly : subcutaneous injection, 2mg, once a week
|
Insulin Detemir
n=105 Participants
Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day
|
|---|---|---|
|
Percentage of Patients Achieving Glycosylated Hemoglobin (HbA1c) Concentration ≤7.0% With Weight Loss (≥1.0 kg) at Endpoint (Week 26)
|
44.1 Percentage
Interval 34.7 to 53.9
|
11.4 Percentage
Interval 6.0 to 19.1
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: 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.
Percentage of patients who have achieved HbA1c ≤7.4% with weight loss (≥1.0 kg) at endpoint (Week 26)
Outcome measures
| Measure |
Exenatide Once Weekly
n=107 Participants
Exenatide once weekly : subcutaneous injection, 2mg, once a week
|
Insulin Detemir
n=101 Participants
Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day
|
|---|---|---|
|
Percentage of Patients Who Have Achieved HbA1c ≤7.4% With Weight Loss (≥1.0 kg) at Endpoint (Week 26)
|
58.9 Percentage
Interval 49.0 to 68.3
|
17.8 Percentage
Interval 10.9 to 26.7
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: The analysis was done for the FAS population (as randomised).
Change in HbA1c from baseline to week 26
Outcome measures
| Measure |
Exenatide Once Weekly
n=95 Participants
Exenatide once weekly : subcutaneous injection, 2mg, once a week
|
Insulin Detemir
n=96 Participants
Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day
|
|---|---|---|
|
Change in HbA1c From Baseline to Week 26
|
-1.32 Percentage of total hemoglobin
Standard Error 0.076
|
-0.91 Percentage of total hemoglobin
Standard Error 0.077
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: The analysis was done for the FAS population (as randomised).
Change in body weight from baseline to week 26
Outcome measures
| Measure |
Exenatide Once Weekly
n=96 Participants
Exenatide once weekly : subcutaneous injection, 2mg, once a week
|
Insulin Detemir
n=98 Participants
Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day
|
|---|---|---|
|
Change in Body Weight From Baseline to Week 26
|
-2.79 kilograms
Standard Error 0.347
|
0.88 kilograms
Standard Error 0.351
|
SECONDARY outcome
Timeframe: Week 26Population: 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.
Percentage of patients who have achieved HbA1c ≤.7.4% at endpoint
Outcome measures
| Measure |
Exenatide Once Weekly
n=111 Participants
Exenatide once weekly : subcutaneous injection, 2mg, once a week
|
Insulin Detemir
n=105 Participants
Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day
|
|---|---|---|
|
Percentage of Patients Achieving HbA1c ≤7.4% at Endpoint
|
66.7 Percentage
Interval 57.1 to 75.3
|
54.3 Percentage
Interval 44.3 to 64.0
|
SECONDARY outcome
Timeframe: Week 26Population: 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.
Percentage of patients achieving ≤7.0% at endpoint.
Outcome measures
| Measure |
Exenatide Once Weekly
n=111 Participants
Exenatide once weekly : subcutaneous injection, 2mg, once a week
|
Insulin Detemir
n=105 Participants
Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day
|
|---|---|---|
|
Percentage of Patients Achieving ≤7.0% at Endpoint
|
51.4 Percentage
Interval 41.7 to 61.0
|
34.3 Percentage
Interval 25.3 to 44.2
|
SECONDARY outcome
Timeframe: Week 26Population: 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.
Percentage of patients achieving HbA1c ≤6.5% at endpoint
Outcome measures
| Measure |
Exenatide Once Weekly
n=111 Participants
Exenatide once weekly : subcutaneous injection, 2mg, once a week
|
Insulin Detemir
n=105 Participants
Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day
|
|---|---|---|
|
Percentage of Patients Achieving ≤6.5% at Endpoint
|
27.9 Percentage
Interval 19.8 to 37.2
|
7.6 Percentage
Interval 3.3 to 14.5
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: 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.
Change in fasting serum glucose from baseline to endpoint (Week 26).
Outcome measures
| Measure |
Exenatide Once Weekly
n=108 Participants
Exenatide once weekly : subcutaneous injection, 2mg, once a week
|
Insulin Detemir
n=104 Participants
Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day
|
|---|---|---|
|
Change in Fasting Serum Glucose From Baseline to Endpoint (Week 26).
|
-2.33 mmol/L
Standard Error 0.191
|
-2.43 mmol/L
Standard Error 0.196
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: The analysis was done for the FAS population (as randomised).
Change in systolic blood pressure from baseline to Week 26
Outcome measures
| Measure |
Exenatide Once Weekly
n=95 Participants
Exenatide once weekly : subcutaneous injection, 2mg, once a week
|
Insulin Detemir
n=98 Participants
Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day
|
|---|---|---|
|
Changes in Systolic Blood Pressure From Baseline to Week 26
|
-7.37 mmHg
Standard Error 1.342
|
-2.65 mmHg
Standard Error 1.339
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: The analysis was done for the FAS population (as randomised).
Change in diastolic blood pressure from baseline to week 26.
Outcome measures
| Measure |
Exenatide Once Weekly
n=95 Participants
Exenatide once weekly : subcutaneous injection, 2mg, once a week
|
Insulin Detemir
n=98 Participants
Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day
|
|---|---|---|
|
Change in Diastolic Blood Pressure From Baseline to Week 26.
|
-0.79 mmHg
Standard Error 0.855 • Interval -1.79 to 0.56
|
-0.34 mmHg
Standard Error 0.859 • Interval -2.05 to 0.39
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: 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.
Change in total cholesterol from baseline to endpoint (week 26).
Outcome measures
| Measure |
Exenatide Once Weekly
n=105 Participants
Exenatide once weekly : subcutaneous injection, 2mg, once a week
|
Insulin Detemir
n=100 Participants
Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day
|
|---|---|---|
|
Change in Total Cholesterol From Baseline to Endpoint (Week 26).
|
-0.09 mmol/L
Standard Error 0.067 • Interval -0.22 to 0.04
|
0.06 mmol/L
Standard Error 0.068 • Interval -0.08 to 0.19
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: 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.
Change in High-density lipoprotein (HDL) cholesterol from baseline to endpoint (week 26).
Outcome measures
| Measure |
Exenatide Once Weekly
n=105 Participants
Exenatide once weekly : subcutaneous injection, 2mg, once a week
|
Insulin Detemir
n=100 Participants
Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day
|
|---|---|---|
|
Change in High-density Lipoprotein (HDL) Cholesterol From Baseline to Endpoint (Week 26).
|
0.02 mmol/L
Standard Error 0.014 • Interval -0.01 to 0.05
|
0.04 mmol/L
Standard Error 0.015 • Interval 0.01 to 0.06
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: 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.
Change in triglycerides from baseline to endpoint (week 26).
Outcome measures
| Measure |
Exenatide Once Weekly
n=105 Participants
Exenatide once weekly : subcutaneous injection, 2mg, once a week
|
Insulin Detemir
n=100 Participants
Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day
|
|---|---|---|
|
Change in Triglycerides From Baseline to Endpoint (Week 26).
|
-0.01 mmol/L
Standard Error 0.079 • Interval -0.17 to 0.15
|
-0.08 mmol/L
Standard Error 0.081 • Interval -0.24 to 0.08
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: Full analysis set (as randomized).
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.
Outcome measures
| Measure |
Exenatide Once Weekly
n=111 Participants
Exenatide once weekly : subcutaneous injection, 2mg, once a week
|
Insulin Detemir
n=105 Participants
Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day
|
|---|---|---|
|
Hypoglycemia Rate Per Year
|
0.06 events per subject-year
Interval 0.02 to 0.2
|
0.10 events per subject-year
Interval 0.03 to 0.3
|
Adverse Events
Exenatide Once Weekly
Insulin Detemir
Serious adverse events
| Measure |
Exenatide Once Weekly
n=111 participants at risk
Exenatide once weekly : subcutaneous injection, 2mg, once a week
|
Insulin Detemir
n=105 participants at risk
Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day
|
|---|---|---|
|
Cardiac disorders
Atrioventricular block second degree
|
0.90%
1/111
|
0.00%
0/105
|
|
Cardiac disorders
Ventricular extrasystoles
|
0.90%
1/111
|
0.00%
0/105
|
|
General disorders
Chest discomfort
|
0.90%
1/111
|
0.95%
1/105
|
|
General disorders
Chest pain
|
0.00%
0/111
|
1.9%
2/105
|
|
Infections and infestations
Pneumonia
|
0.00%
0/111
|
0.95%
1/105
|
|
Injury, poisoning and procedural complications
Joint sprain
|
0.90%
1/111
|
0.00%
0/105
|
|
Investigations
Blood amylase increased
|
0.90%
1/111
|
0.00%
0/105
|
|
Investigations
Lipase increased
|
0.90%
1/111
|
0.00%
0/105
|
|
Musculoskeletal and connective tissue disorders
Bursitis
|
0.90%
1/111
|
0.00%
0/105
|
|
Musculoskeletal and connective tissue disorders
Myositis
|
0.90%
1/111
|
0.00%
0/105
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Small cell lung cancer stage unspecified
|
0.00%
0/111
|
0.95%
1/105
|
|
Renal and urinary disorders
Renal injury
|
0.00%
0/111
|
0.95%
1/105
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/111
|
0.95%
1/105
|
Other adverse events
| Measure |
Exenatide Once Weekly
n=111 participants at risk
Exenatide once weekly : subcutaneous injection, 2mg, once a week
|
Insulin Detemir
n=105 participants at risk
Insulin detemir : subcutaneous injection, with dosage titrated according to the detemir label and published titration schedule, once or twice a day
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
47.7%
53/111
|
11.4%
12/105
|
|
Gastrointestinal disorders
Diarrhoea
|
17.1%
19/111
|
10.5%
11/105
|
|
Gastrointestinal disorders
Vomiting
|
14.4%
16/111
|
8.6%
9/105
|
|
Gastrointestinal disorders
Constipation
|
9.0%
10/111
|
2.9%
3/105
|
|
Gastrointestinal disorders
Dyspepsia
|
6.3%
7/111
|
0.95%
1/105
|
|
General disorders
Injection site nodule
|
19.8%
22/111
|
0.00%
0/105
|
|
General disorders
Injection site pruritus
|
10.8%
12/111
|
0.95%
1/105
|
|
General disorders
Malaise
|
5.4%
6/111
|
1.9%
2/105
|
|
Infections and infestations
Nasopharyngitis
|
20.7%
23/111
|
29.5%
31/105
|
|
Infections and infestations
Lower respiratory tract infection
|
4.5%
5/111
|
5.7%
6/105
|
|
Infections and infestations
Influenza
|
1.8%
2/111
|
5.7%
6/105
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
8.1%
9/111
|
6.7%
7/105
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal
|
6.3%
7/111
|
1.9%
2/105
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
5.4%
6/111
|
2.9%
3/105
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
4.5%
5/111
|
5.7%
6/105
|
|
Nervous system disorders
Headache
|
20.7%
23/111
|
14.3%
15/105
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.3%
7/111
|
8.6%
9/105
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
3.6%
4/111
|
7.6%
8/105
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place