Trial Outcomes & Findings for Exenatide Compared With Twice-Daily Biphasic Insulin Aspart in Patients With Type 2 Diabetes Using Sulfonylurea and Metformin (NCT NCT00082407)
NCT ID: NCT00082407
Last Updated: 2015-04-07
Results Overview
Change in HbA1c from baseline to week 52
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
505 participants
Primary outcome timeframe
baseline, week 52
Results posted on
2015-04-07
Participant Flow
Four patients withdrew from the study prior to receiving study drug.
Participant milestones
| Measure |
Exenatide Arm
subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 48 weeks
|
Biphasic Insulin Aspart Arm
subcutaneous injection, twice daily; titration to target blood glucose level
|
|---|---|---|
|
Overall Study
STARTED
|
255
|
250
|
|
Overall Study
Received Treatment (Intent to Treat)
|
253
|
248
|
|
Overall Study
COMPLETED
|
199
|
223
|
|
Overall Study
NOT COMPLETED
|
56
|
27
|
Reasons for withdrawal
| Measure |
Exenatide Arm
subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 48 weeks
|
Biphasic Insulin Aspart Arm
subcutaneous injection, twice daily; titration to target blood glucose level
|
|---|---|---|
|
Overall Study
Adverse Event
|
20
|
0
|
|
Overall Study
Protocol Violation
|
14
|
12
|
|
Overall Study
Patient Decision
|
13
|
6
|
|
Overall Study
Physician Decision
|
5
|
3
|
|
Overall Study
Loss of Glucose Control
|
2
|
2
|
|
Overall Study
Death
|
2
|
1
|
|
Overall Study
Lost to Follow-up
|
0
|
3
|
Baseline Characteristics
Exenatide Compared With Twice-Daily Biphasic Insulin Aspart in Patients With Type 2 Diabetes Using Sulfonylurea and Metformin
Baseline characteristics by cohort
| Measure |
Exenatide Arm
n=253 Participants
subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 48 weeks
|
Biphasic Insulin Aspart Arm
n=248 Participants
subcutaneous injection, twice daily; titration to target blood glucose level
|
Total
n=501 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
|
184 Participants
n=5 Participants
|
174 Participants
n=7 Participants
|
358 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
69 Participants
n=5 Participants
|
74 Participants
n=7 Participants
|
143 Participants
n=5 Participants
|
|
Age, Continuous
|
58.8 years
STANDARD_DEVIATION 8.7 • n=5 Participants
|
58.5 years
STANDARD_DEVIATION 9.2 • n=7 Participants
|
58.7 years
STANDARD_DEVIATION 9.0 • n=5 Participants
|
|
Sex: Female, Male
Female
|
135 Participants
n=5 Participants
|
122 Participants
n=7 Participants
|
257 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
118 Participants
n=5 Participants
|
126 Participants
n=7 Participants
|
244 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: baseline, week 52Population: Last Observation Carried Forward; Intent to Treat, computed from the patients having both baseline and post-baseline data.
Change in HbA1c from baseline to week 52
Outcome measures
| Measure |
Exenatide Arm
n=248 Participants
subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 48 weeks
|
Biphasic Insulin Aspart Arm
n=246 Participants
subcutaneous injection, twice daily; titration to target blood glucose level
|
|---|---|---|
|
Change in Glcosylated Hemoglobin (HbA1c)
Baseline HbA1c
|
8.59 percentage
Standard Error 0.07
|
8.65 percentage
Standard Error 0.07
|
|
Change in Glcosylated Hemoglobin (HbA1c)
Change in HbA1c at week 52
|
-0.98 percentage
Standard Error 0.07
|
-0.88 percentage
Standard Error 0.07
|
SECONDARY outcome
Timeframe: 52 weeksPopulation: Last Observation Carried Forward; Intent to Treat
Percentage of patients in each arm who had HbA1c \>7% at baseline and had HbA1c \<=7% at week 52 (percentage = \[number of subjects with HbA1c \<=7% at week 52 divided by number of subjects with HbA1c \>7% at baseline\] \* 100%).
Outcome measures
| Measure |
Exenatide Arm
n=227 Participants
subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 48 weeks
|
Biphasic Insulin Aspart Arm
n=237 Participants
subcutaneous injection, twice daily; titration to target blood glucose level
|
|---|---|---|
|
Percentage of Patients Achieving HbA1c <=7%
|
31.7 percentage of participants
|
24.1 percentage of participants
|
SECONDARY outcome
Timeframe: baseline, week 52Population: Intent to Treat, computed from the patients having both baseline and week 52 data.
Change in body weight from baseline to week 52.
Outcome measures
| Measure |
Exenatide Arm
n=205 Participants
subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 48 weeks
|
Biphasic Insulin Aspart Arm
n=223 Participants
subcutaneous injection, twice daily; titration to target blood glucose level
|
|---|---|---|
|
Change in Body Weight
Baseline body weight
|
85.51 kg
Standard Error 0.99
|
83.38 kg
Standard Error 0.99
|
|
Change in Body Weight
Change in body weight at week 52
|
-2.54 kg
Standard Error 0.17
|
2.92 kg
Standard Error 0.17
|
SECONDARY outcome
Timeframe: baseline, week 52Population: Intent to Treat, computed from the patients having both baseline and week 52 data.
Change in fasting serum glucose from baseline to week 52
Outcome measures
| Measure |
Exenatide Arm
n=198 Participants
subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 48 weeks
|
Biphasic Insulin Aspart Arm
n=218 Participants
subcutaneous injection, twice daily; titration to target blood glucose level
|
|---|---|---|
|
Change in Fasting Serum Glucose
Baseline fasting serum glucose
|
11.00 mmol/L
Standard Error 0.18
|
11.30 mmol/L
Standard Error 0.18
|
|
Change in Fasting Serum Glucose
Change in fasting serum glucose at week 52
|
-1.75 mmol/L
Standard Error 0.19
|
-1.64 mmol/L
Standard Error 0.19
|
SECONDARY outcome
Timeframe: baseline, week 52Population: Last Observation Carried Forward; Intent to Treat
Change in 7-point (pre-breakfast, after breakfast, pre-lunch, after lunch, pre-dinner, after dinner, 0300 hours) SMBG profile from baseline to week 52
Outcome measures
| Measure |
Exenatide Arm
n=253 Participants
subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 48 weeks
|
Biphasic Insulin Aspart Arm
n=248 Participants
subcutaneous injection, twice daily; titration to target blood glucose level
|
|---|---|---|
|
Change in 7-point Self-monitored Blood Glucose (SMBG) Profile
Pre-breakfast: Baseline SMBG
|
9.57 mmol/L
Standard Deviation 2.34
|
9.86 mmol/L
Standard Deviation 2.65
|
|
Change in 7-point Self-monitored Blood Glucose (SMBG) Profile
Pre-breakfast: Change in SMBG at week 52
|
-1.15 mmol/L
Standard Deviation 2.60
|
-1.68 mmol/L
Standard Deviation 2.33
|
|
Change in 7-point Self-monitored Blood Glucose (SMBG) Profile
After breakfast: Baseline SMBG
|
12.30 mmol/L
Standard Deviation 3.02
|
12.71 mmol/L
Standard Deviation 3.03
|
|
Change in 7-point Self-monitored Blood Glucose (SMBG) Profile
After breakfast: Change in SMBG at week 52
|
-3.83 mmol/L
Standard Deviation 3.30
|
-3.06 mmol/L
Standard Deviation 3.26
|
|
Change in 7-point Self-monitored Blood Glucose (SMBG) Profile
Pre-lunch: Baseline SMBG
|
9.38 mmol/L
Standard Deviation 2.86
|
9.86 mmol/L
Standard Deviation 3.30
|
|
Change in 7-point Self-monitored Blood Glucose (SMBG) Profile
Pre-lunch: Change in SMBG at week 52
|
-1.47 mmol/L
Standard Deviation 3.01
|
-2.40 mmol/L
Standard Deviation 3.44
|
|
Change in 7-point Self-monitored Blood Glucose (SMBG) Profile
After lunch: Baseline SMBG
|
11.18 mmol/L
Standard Deviation 3.14
|
11.39 mmol/L
Standard Deviation 3.58
|
|
Change in 7-point Self-monitored Blood Glucose (SMBG) Profile
After lunch: Change in SMBG at week 52
|
-1.72 mmol/L
Standard Deviation 3.48
|
-1.76 mmol/L
Standard Deviation 3.74
|
|
Change in 7-point Self-monitored Blood Glucose (SMBG) Profile
Pre-dinner: Baseline SMBG
|
9.35 mmol/L
Standard Deviation 2.86
|
9.57 mmol/L
Standard Deviation 3.03
|
|
Change in 7-point Self-monitored Blood Glucose (SMBG) Profile
Pre-dinner: Change in SMBG at week 52
|
-1.06 mmol/L
Standard Deviation 3.25
|
-1.52 mmol/L
Standard Deviation 3.42
|
|
Change in 7-point Self-monitored Blood Glucose (SMBG) Profile
After dinner: Baseline SMBG
|
11.25 mmol/L
Standard Deviation 3.04
|
11.68 mmol/L
Standard Deviation 3.27
|
|
Change in 7-point Self-monitored Blood Glucose (SMBG) Profile
After dinner: Change in SMBG at week 52
|
-3.11 mmol/L
Standard Deviation 3.76
|
-2.44 mmol/L
Standard Deviation 3.69
|
|
Change in 7-point Self-monitored Blood Glucose (SMBG) Profile
3:00 AM: Baseline SMBG
|
9.08 mmol/L
Standard Deviation 2.63
|
9.58 mmol/L
Standard Deviation 3.14
|
|
Change in 7-point Self-monitored Blood Glucose (SMBG) Profile
3:00 AM: Change in SMBG at week 52
|
-0.96 mmol/L
Standard Deviation 3.14
|
-1.95 mmol/L
Standard Deviation 3.13
|
SECONDARY outcome
Timeframe: 52 weeksPopulation: Intent to Treat
Percentage of patients who experienced at least one episode of hypoglycemia at any point during the 52 week Parent Study (incidence of hypoglycemia = number of patients who experienced at least one episode of hypoglycemia at any point during the 52 week Parent Study divided by the total number of patients who particiapted in the 52 week Parent Study
Outcome measures
| Measure |
Exenatide Arm
n=253 Participants
subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 48 weeks
|
Biphasic Insulin Aspart Arm
n=248 Participants
subcutaneous injection, twice daily; titration to target blood glucose level
|
|---|---|---|
|
Percentage of Patients With Hypoglycemic Events
|
53.0 percentage of participants
|
51.6 percentage of participants
|
SECONDARY outcome
Timeframe: baseline, week 52Population: Last Observation Carried Forward; Intent to Treat
Change in rate of hypoglycemic events per 30 days per patient from baseline to week 52
Outcome measures
| Measure |
Exenatide Arm
n=253 Participants
subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 48 weeks
|
Biphasic Insulin Aspart Arm
n=248 Participants
subcutaneous injection, twice daily; titration to target blood glucose level
|
|---|---|---|
|
Change in Rate of Hypoglycemic Events
Change in event rate at week 52
|
0.19 events per 30 days per patient
Standard Error 0.06
|
0.26 events per 30 days per patient
Standard Error 0.06
|
|
Change in Rate of Hypoglycemic Events
Baseline event rate
|
0.22 events per 30 days per patient
Standard Error 0.07
|
0.18 events per 30 days per patient
Standard Error 0.07
|
Adverse Events
Exenatide Arm
Serious events: 19 serious events
Other events: 179 other events
Deaths: 0 deaths
Biphasic Insulin Aspart Arm
Serious events: 11 serious events
Other events: 128 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Exenatide Arm
subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 48 weeks
|
Biphasic Insulin Aspart Arm
subcutaneous injection, twice daily; titration to target blood glucose level
|
|---|---|---|
|
Blood and lymphatic system disorders
Anemia
|
0.79%
2/253
|
0.00%
0/248
|
|
Cardiac disorders
Angina pectoris
|
0.79%
2/253
|
0.00%
0/248
|
|
Cardiac disorders
Myocardial infarction
|
0.79%
2/253
|
0.00%
0/248
|
|
Cardiac disorders
Atrial fibrillation
|
0.40%
1/253
|
0.00%
0/248
|
|
Cardiac disorders
Coronary artery disease
|
0.40%
1/253
|
0.00%
0/248
|
|
Cardiac disorders
Acute coronary syndrome
|
0.00%
0/253
|
0.40%
1/248
|
|
Cardiac disorders
Atrial flutter
|
0.00%
0/253
|
0.40%
1/248
|
|
Cardiac disorders
Bundle branch block left
|
0.00%
0/253
|
0.40%
1/248
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/253
|
0.40%
1/248
|
|
Gastrointestinal disorders
Gastrointestinal hemorrhage
|
0.40%
1/253
|
0.00%
0/248
|
|
Gastrointestinal disorders
Nausea
|
0.40%
1/253
|
0.00%
0/248
|
|
Gastrointestinal disorders
Anal fistula
|
0.00%
0/253
|
0.40%
1/248
|
|
General disorders
Asthenia
|
0.40%
1/253
|
0.00%
0/248
|
|
General disorders
Calcinosis
|
0.40%
1/253
|
0.00%
0/248
|
|
General disorders
Gait disturbance
|
0.40%
1/253
|
0.00%
0/248
|
|
Infections and infestations
Abdominal wall abscess
|
0.40%
1/253
|
0.00%
0/248
|
|
Infections and infestations
Appendicitis
|
0.40%
1/253
|
0.00%
0/248
|
|
Infections and infestations
Cellulitus
|
0.40%
1/253
|
0.00%
0/248
|
|
Infections and infestations
Injection site cellulitus
|
0.40%
1/253
|
0.00%
0/248
|
|
Infections and infestations
Lobar pneumonia
|
0.00%
0/253
|
0.40%
1/248
|
|
Injury, poisoning and procedural complications
Fall
|
0.40%
1/253
|
0.00%
0/248
|
|
Injury, poisoning and procedural complications
Radius fracture
|
0.40%
1/253
|
0.00%
0/248
|
|
Investigations
Weight decreased
|
0.40%
1/253
|
0.00%
0/248
|
|
Metabolism and nutrition disorders
Anorexia
|
0.40%
1/253
|
0.00%
0/248
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.79%
2/253
|
0.00%
0/248
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.40%
1/253
|
0.00%
0/248
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/253
|
0.40%
1/248
|
|
Musculoskeletal and connective tissue disorders
Spinal osteoarthritis
|
0.00%
0/253
|
0.40%
1/248
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Fibroadenoma of breast
|
0.00%
0/253
|
0.40%
1/248
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.00%
0/253
|
0.40%
1/248
|
|
Nervous system disorders
Cognitive disorder
|
0.40%
1/253
|
0.00%
0/248
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/253
|
0.40%
1/248
|
|
Psychiatric disorders
Major depression
|
0.40%
1/253
|
0.00%
0/248
|
|
Renal and urinary disorders
Urinary incontinence
|
0.00%
0/253
|
0.40%
1/248
|
|
Reproductive system and breast disorders
Benign prostatic hyperplasia
|
0.40%
1/253
|
0.00%
0/248
|
|
Reproductive system and breast disorders
Breast microcalcification
|
0.00%
0/253
|
0.40%
1/248
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngeal mass
|
0.40%
1/253
|
0.00%
0/248
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary edema
|
0.00%
0/253
|
0.40%
1/248
|
|
Vascular disorders
Hematoma
|
0.40%
1/253
|
0.00%
0/248
|
|
Vascular disorders
Hypertension
|
0.40%
1/253
|
0.00%
0/248
|
|
Vascular disorders
Peripheral ischemia
|
0.40%
1/253
|
0.00%
0/248
|
Other adverse events
| Measure |
Exenatide Arm
subcutaneous injection, twice daily; 5 mcg for 4 weeks followed by 10 mcg for 48 weeks
|
Biphasic Insulin Aspart Arm
subcutaneous injection, twice daily; titration to target blood glucose level
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
33.2%
84/253
|
0.40%
1/248
|
|
Gastrointestinal disorders
Vomiting
|
15.0%
38/253
|
3.2%
8/248
|
|
Infections and infestations
Nasopharyngitis
|
11.1%
28/253
|
9.7%
24/248
|
|
Gastrointestinal disorders
Diarrhea
|
9.5%
24/253
|
2.0%
5/248
|
|
Infections and infestations
Influenza
|
7.1%
18/253
|
6.5%
16/248
|
|
Nervous system disorders
Headache
|
4.7%
12/253
|
5.2%
13/248
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
53.0%
134/253
|
51.6%
128/248
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60