Trial Outcomes & Findings for Effect of AC2993 Compared With Insulin Glargine in Patients With Type 2 Diabetes Also Using Combination Therapy With Sulfonylurea and Metformin (NCT NCT00082381)
NCT ID: NCT00082381
Last Updated: 2015-04-07
Results Overview
Change in HbA1c from baseline to week 26
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
551 participants
Primary outcome timeframe
Baseline, week 26
Results posted on
2015-04-07
Participant Flow
Two patients were lost to follow-up after receiving study drug, and it is not known if they took at least one dose of the drug. For purposes of data analysis, these patients were classified as untreated.
Participant milestones
| Measure |
Exenatide Arm
Exenatide subcutaneous injection twice daily for 26 weeks (5mcg for 4 weeks followed by 10mcg for 22 weeks)
|
Insulin Glargine Arm
Insulin glargine subcutaneous injection once daily for 26 weeks (forced titration to target blood glucose level)
|
|---|---|---|
|
Overall Study
STARTED
|
283
|
268
|
|
Overall Study
Received Treatment (Intent to Treat)
|
282
|
267
|
|
Overall Study
COMPLETED
|
228
|
242
|
|
Overall Study
NOT COMPLETED
|
55
|
26
|
Reasons for withdrawal
| Measure |
Exenatide Arm
Exenatide subcutaneous injection twice daily for 26 weeks (5mcg for 4 weeks followed by 10mcg for 22 weeks)
|
Insulin Glargine Arm
Insulin glargine subcutaneous injection once daily for 26 weeks (forced titration to target blood glucose level)
|
|---|---|---|
|
Overall Study
Adverse Event
|
27
|
2
|
|
Overall Study
Lost to Follow-up
|
5
|
7
|
|
Overall Study
Patient Decision
|
8
|
4
|
|
Overall Study
Physician Decision
|
1
|
2
|
|
Overall Study
Protocol Violation
|
10
|
11
|
|
Overall Study
Loss of Glucose Control
|
4
|
0
|
Baseline Characteristics
Effect of AC2993 Compared With Insulin Glargine in Patients With Type 2 Diabetes Also Using Combination Therapy With Sulfonylurea and Metformin
Baseline characteristics by cohort
| Measure |
Exenatide Arm
n=282 Participants
Exenatide subcutaneous injection twice daily for 26 weeks (5mcg for 4 weeks followed by 10mcg for 22 weeks)
|
Insulin Glargine Arm
n=267 Participants
Insulin glargine subcutaneous injection once daily for 26 weeks (forced titration to target blood glucose level)
|
Total
n=549 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
59.80 years
STANDARD_DEVIATION 8.82 • n=5 Participants
|
57.96 years
STANDARD_DEVIATION 9.46 • n=7 Participants
|
58.91 years
STANDARD_DEVIATION 9.13 • n=5 Participants
|
|
Sex: Female, Male
Female
|
127 Participants
n=5 Participants
|
116 Participants
n=7 Participants
|
243 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
155 Participants
n=5 Participants
|
151 Participants
n=7 Participants
|
306 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, week 26Population: 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 26
Outcome measures
| Measure |
Exenatide Arm
n=275 Participants
Exenatide subcutaneous injection twice daily for 26 weeks (5mcg for 4 weeks followed by 10mcg for 22 weeks)
|
Insulin Glargine Arm
n=260 Participants
Insulin glargine subcutaneous injection once daily for 26 weeks (forced titration to target blood glucose level)
|
|---|---|---|
|
Change in Glycosylated Hemoglobin (HbA1c)
Baseline HbA1c
|
8.13 percentage
Standard Error 0.07
|
8.19 percentage
Standard Error 0.07
|
|
Change in Glycosylated Hemoglobin (HbA1c)
Change in HbA1c at week 26
|
-1.00 percentage
Standard Error 0.06
|
-1.05 percentage
Standard Error 0.06
|
SECONDARY outcome
Timeframe: 26 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 26 (percentage = \[number of subjects with HbA1c \<=7% at week 26 divided by number of subjects with HbA1c \>7% at baseline\] \* 100%).
Outcome measures
| Measure |
Exenatide Arm
n=282 Participants
Exenatide subcutaneous injection twice daily for 26 weeks (5mcg for 4 weeks followed by 10mcg for 22 weeks)
|
Insulin Glargine Arm
n=267 Participants
Insulin glargine subcutaneous injection once daily for 26 weeks (forced titration to target blood glucose level)
|
|---|---|---|
|
Percentage of Patients Achieving HbA1c <=7%
|
46.43 percentage of participants
|
48.03 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, week 26Population: Intent to Treat
Change in body weight from baseline to week 26
Outcome measures
| Measure |
Exenatide Arm
n=231 Participants
Exenatide subcutaneous injection twice daily for 26 weeks (5mcg for 4 weeks followed by 10mcg for 22 weeks)
|
Insulin Glargine Arm
n=244 Participants
Insulin glargine subcutaneous injection once daily for 26 weeks (forced titration to target blood glucose level)
|
|---|---|---|
|
Change in Body Weight
Baseline body weight
|
88.42 kg
Standard Error 1.16
|
89.25 kg
Standard Error 1.20
|
|
Change in Body Weight
Change in body weight at week 26
|
-2.32 kg
Standard Error 0.21
|
1.75 kg
Standard Error 0.21
|
SECONDARY outcome
Timeframe: Baseline, week 26Population: Last Observation Carried Forward; Intent to Treat
Change in fasting serum glucose from baseline to week 26
Outcome measures
| Measure |
Exenatide Arm
n=258 Participants
Exenatide subcutaneous injection twice daily for 26 weeks (5mcg for 4 weeks followed by 10mcg for 22 weeks)
|
Insulin Glargine Arm
n=245 Participants
Insulin glargine subcutaneous injection once daily for 26 weeks (forced titration to target blood glucose level)
|
|---|---|---|
|
Change in Fasting Serum Glucose
Baseline fasting serum glucose
|
10.27 mmol/L
Standard Error 0.21
|
10.46 mmol/L
Standard Error 0.21
|
|
Change in Fasting Serum Glucose
Change in fasting serum glucose at week 26
|
-1.22 mmol/L
Standard Error 0.19
|
-2.86 mmol/L
Standard Error 0.19
|
SECONDARY outcome
Timeframe: Baseline, week 26Population: Last Observation Carried Forward; Intent to Treat
Change in 7-point (pre-breakfast, 2 hour post breakfast, pre-lunch, 2 hour post lunch, pre-dinner, 2 hour post dinner, 0300 hours) SMBG profile from baseline to week 26
Outcome measures
| Measure |
Exenatide Arm
n=282 Participants
Exenatide subcutaneous injection twice daily for 26 weeks (5mcg for 4 weeks followed by 10mcg for 22 weeks)
|
Insulin Glargine Arm
n=267 Participants
Insulin glargine subcutaneous injection once daily for 26 weeks (forced titration to target blood glucose level)
|
|---|---|---|
|
Change in 7-point Self-monitored Blood Glucose (SMBG) Profile
Pre-breakfast: Change in SMBG at week 26
|
-1.25 mmol/L
Standard Error 0.130
|
-2.56 mmol/L
Standard Error 0.132
|
|
Change in 7-point Self-monitored Blood Glucose (SMBG) Profile
2hr post breatfast: Baseline SMBG
|
12.51 mmol/L
Standard Error 0.220
|
12.36 mmol/L
Standard Error 0.226
|
|
Change in 7-point Self-monitored Blood Glucose (SMBG) Profile
2hr post breakfast: Change in SMBG at week 26
|
-3.77 mmol/L
Standard Error 0.171
|
-2.86 mmol/L
Standard Error 0.174
|
|
Change in 7-point Self-monitored Blood Glucose (SMBG) Profile
Pre-lunch: Baseline SMBG
|
9.61 mmol/L
Standard Error 0.218
|
9.47 mmol/L
Standard Error 0.224
|
|
Change in 7-point Self-monitored Blood Glucose (SMBG) Profile
Pre-lunch: Change in SMBG at week 26
|
-1.50 mmol/L
Standard Error 0.156
|
-1.93 mmol/L
Standard Error 0.158
|
|
Change in 7-point Self-monitored Blood Glucose (SMBG) Profile
2hr post lunch: Baseline SMBG
|
11.15 mmol/L
Standard Error 0.222
|
10.96 mmol/L
Standard Error 0.226
|
|
Change in 7-point Self-monitored Blood Glucose (SMBG) Profile
2hr post lunch: Change in SMBG at week 26
|
-1.68 mmol/L
Standard Error 0.173
|
-1.69 mmol/L
Standard Error 0.176
|
|
Change in 7-point Self-monitored Blood Glucose (SMBG) Profile
Pre-dinner: Baseline SMBG
|
9.46 mmol/L
Standard Error 0.211
|
9.35 mmol/L
Standard Error 0.216
|
|
Change in 7-point Self-monitored Blood Glucose (SMBG) Profile
Pre-dinner: Change in SMBG at week 26
|
-1.15 mmol/L
Standard Error 0.156
|
-1.72 mmol/L
Standard Error 0.159
|
|
Change in 7-point Self-monitored Blood Glucose (SMBG) Profile
2hr post dinner: Baseline SMBG
|
11.17 mmol/L
Standard Error 0.206
|
11.49 mmol/L
Standard Error 0.211
|
|
Change in 7-point Self-monitored Blood Glucose (SMBG) Profile
2hr post dinner: Change in SMBG at week 26
|
-3.06 mmol/L
Standard Error 0.172
|
-1.65 mmol/L
Standard Error 0.175
|
|
Change in 7-point Self-monitored Blood Glucose (SMBG) Profile
3:00 AM: Baseline SMBG
|
9.02 mmol/L
Standard Error 0.189
|
9.36 mmol/L
Standard Error 0.192
|
|
Change in 7-point Self-monitored Blood Glucose (SMBG) Profile
3:00 AM: Change in SMBG at week 26
|
-1.05 mmol/L
Standard Error 0.169
|
-1.97 mmol/L
Standard Error 0.169
|
|
Change in 7-point Self-monitored Blood Glucose (SMBG) Profile
Pre-breakfast: Baseline SMBG
|
9.47 mmol/L
Standard Error 0.169
|
9.50 mmol/L
Standard Error 0.173
|
SECONDARY outcome
Timeframe: 26 weeksPopulation: Intent to Treat
Percentage of patients who experienced at least one episode of hypoglycemia at any point during the 26 week Parent Study (incidence of hypoglycemia = number of patients who experienced at least one episode of hypoglycemia at any point during the 26 week Parent Study divided by the total number of patients who participated in the 26 week Parent Study
Outcome measures
| Measure |
Exenatide Arm
n=282 Participants
Exenatide subcutaneous injection twice daily for 26 weeks (5mcg for 4 weeks followed by 10mcg for 22 weeks)
|
Insulin Glargine Arm
n=267 Participants
Insulin glargine subcutaneous injection once daily for 26 weeks (forced titration to target blood glucose level)
|
|---|---|---|
|
Percentage of Patients With Hypoglycemic Events
|
55.32 percentage of participants
|
59.93 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, week 26Population: Intent to Treat
Change in rate of hypoglycemic events per 30 days per patient from baseline to week 26
Outcome measures
| Measure |
Exenatide Arm
n=282 Participants
Exenatide subcutaneous injection twice daily for 26 weeks (5mcg for 4 weeks followed by 10mcg for 22 weeks)
|
Insulin Glargine Arm
n=267 Participants
Insulin glargine subcutaneous injection once daily for 26 weeks (forced titration to target blood glucose level)
|
|---|---|---|
|
Change in Rate of Hypoglycemic Events
Baseline event rate
|
0.09 events per 30 days per patient
Standard Error 0.04
|
0.11 events per 30 days per patient
Standard Error 0.04
|
|
Change in Rate of Hypoglycemic Events
Change in event rate at week 26
|
0.23 events per 30 days per patient
Standard Error 0.06
|
0.29 events per 30 days per patient
Standard Error 0.06
|
Adverse Events
Exenatide Arm
Serious events: 8 serious events
Other events: 226 other events
Deaths: 0 deaths
Insulin Glargine Arm
Serious events: 10 serious events
Other events: 160 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Exenatide Arm
Exenatide subcutaneous injection twice daily for 26 weeks (5mcg for 4 weeks followed by 10mcg for 22 weeks)
|
Insulin Glargine Arm
Insulin glargine subcutaneous injection once daily for 26 weeks (forced titration to target blood glucose level)
|
|---|---|---|
|
Vascular disorders
Hypertension
|
0.71%
2/282
|
0.00%
0/267
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/282
|
0.37%
1/267
|
|
Skin and subcutaneous tissue disorders
Angioneurotic edema
|
0.00%
0/282
|
0.37%
1/267
|
|
Cardiac disorders
Atrial fibrillation
|
0.35%
1/282
|
0.00%
0/267
|
|
Renal and urinary disorders
Calculus ureteric
|
0.00%
0/282
|
0.37%
1/267
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.35%
1/282
|
0.00%
0/267
|
|
Cardiac disorders
Coronary artery atherosclerosis
|
0.35%
1/282
|
0.00%
0/267
|
|
Cardiac disorders
Coronary artery disease
|
0.35%
1/282
|
0.00%
0/267
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Dermatofibrosarcoma
|
0.35%
1/282
|
0.00%
0/267
|
|
Infections and infestations
Erysipelas
|
0.00%
0/282
|
0.37%
1/267
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.00%
0/282
|
0.37%
1/267
|
|
Psychiatric disorders
Major depression
|
0.00%
0/282
|
0.37%
1/267
|
|
Reproductive system and breast disorders
Metrorrhagia
|
0.00%
0/282
|
0.37%
1/267
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/282
|
0.37%
1/267
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.00%
0/282
|
0.37%
1/267
|
|
Injury, poisoning and procedural complications
Seroma
|
0.35%
1/282
|
0.00%
0/267
|
|
Nervous system disorders
Syncope
|
0.00%
0/282
|
0.37%
1/267
|
|
Cardiac disorders
Tachyarrhythmia
|
0.35%
1/282
|
0.00%
0/267
|
|
Gastrointestinal disorders
Vomiting
|
0.35%
1/282
|
0.00%
0/267
|
Other adverse events
| Measure |
Exenatide Arm
Exenatide subcutaneous injection twice daily for 26 weeks (5mcg for 4 weeks followed by 10mcg for 22 weeks)
|
Insulin Glargine Arm
Insulin glargine subcutaneous injection once daily for 26 weeks (forced titration to target blood glucose level)
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
57.1%
161/282
|
8.6%
23/267
|
|
Gastrointestinal disorders
Vomiting
|
17.4%
49/282
|
3.7%
10/267
|
|
Nervous system disorders
Headache
|
8.9%
25/282
|
8.6%
23/267
|
|
Infections and infestations
Nasopharyngitis
|
7.8%
22/282
|
9.0%
24/267
|
|
Gastrointestinal disorders
Diarrhea
|
8.5%
24/282
|
3.0%
8/267
|
|
Infections and infestations
Upper respiratory tract infection
|
5.3%
15/282
|
4.9%
13/267
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
6.0%
17/282
|
3.0%
8/267
|
|
Infections and infestations
Influenza
|
2.5%
7/282
|
5.6%
15/267
|
|
Nervous system disorders
Dizziness
|
5.3%
15/282
|
2.2%
6/267
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
55.3%
156/282
|
59.9%
160/267
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60