Trial Outcomes & Findings for Study to Evaluate the Efficacy and Safety of Exenatide Once-Weekly Injection Compared to Once-Daily Insulin in Type 2 Diabetes Mellitus (NCT NCT00935532)
NCT ID: NCT00935532
Last Updated: 2015-06-15
Results Overview
Change in HbA1c from baseline to endpoint (Week 26).
COMPLETED
PHASE3
427 participants
Baseline, Week 26
2015-06-15
Participant Flow
Participant milestones
| Measure |
Exenatide Once Weekly
Subcutaneous injection, 2.0mg, once a week.
|
Insulin Glargine
Subcutaneous injection, titrated to achieve fasting serum glucose target, once a day
|
|---|---|---|
|
Overall Study
STARTED
|
215
|
212
|
|
Overall Study
COMPLETED
|
193
|
201
|
|
Overall Study
NOT COMPLETED
|
22
|
11
|
Reasons for withdrawal
| Measure |
Exenatide Once Weekly
Subcutaneous injection, 2.0mg, once a week.
|
Insulin Glargine
Subcutaneous injection, titrated to achieve fasting serum glucose target, once a day
|
|---|---|---|
|
Overall Study
Adverse Event
|
11
|
6
|
|
Overall Study
Death
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
Physician Decision
|
1
|
2
|
|
Overall Study
Protocol Violation
|
2
|
1
|
|
Overall Study
Subject Decision
|
2
|
1
|
|
Overall Study
Sponsor Decision
|
0
|
1
|
|
Overall Study
Loss Glucose Control
|
4
|
0
|
Baseline Characteristics
Study to Evaluate the Efficacy and Safety of Exenatide Once-Weekly Injection Compared to Once-Daily Insulin in Type 2 Diabetes Mellitus
Baseline characteristics by cohort
| Measure |
Exenatide Once Weekly
n=215 Participants
Subcutaneous injection, 2.0mg, once a week.
|
Insulin Glargine
n=212 Participants
Subcutaneous injection, titrated to achieve fasting serum glucose target, once a day
|
Total
n=427 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
|
160 Participants
n=5 Participants
|
156 Participants
n=7 Participants
|
316 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
55 Participants
n=5 Participants
|
56 Participants
n=7 Participants
|
111 Participants
n=5 Participants
|
|
Age, Continuous
|
57.1 years
STANDARD_DEVIATION 10.44 • n=5 Participants
|
56.4 years
STANDARD_DEVIATION 11.16 • n=7 Participants
|
56.8 years
STANDARD_DEVIATION 10.80 • n=5 Participants
|
|
Sex: Female, Male
Female
|
73 Participants
n=5 Participants
|
64 Participants
n=7 Participants
|
137 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
142 Participants
n=5 Participants
|
148 Participants
n=7 Participants
|
290 Participants
n=5 Participants
|
|
Glycosylated hemoglobin (HbA1c)
|
8.51 percentage of total hemoglobin
STANDARD_DEVIATION 0.823 • n=5 Participants
|
8.50 percentage of total hemoglobin
STANDARD_DEVIATION 0.791 • n=7 Participants
|
8.50 percentage of total hemoglobin
STANDARD_DEVIATION 0.806 • n=5 Participants
|
|
Weight
|
69.95 kg
STANDARD_DEVIATION 13.246 • n=5 Participants
|
71.03 kg
STANDARD_DEVIATION 13.932 • n=7 Participants
|
70.49 kg
STANDARD_DEVIATION 13.586 • n=5 Participants
|
|
Background Oral Antidiabetic Agent (OAD)
Biguanide (BG)
|
145 participants
n=5 Participants
|
142 participants
n=7 Participants
|
287 participants
n=5 Participants
|
|
Background Oral Antidiabetic Agent (OAD)
BG+Thiazolidine Derivative (TZD)
|
70 participants
n=5 Participants
|
70 participants
n=7 Participants
|
140 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 26Population: Statistical analysis of this study was performed for the full analysis set (FAS). FAS consisted of randomized patients who received administration of the study drug at least once and had measurement values after administration. Missing data at endpoint was imputed using last observation carried forward (LOCF) approach.
Change in HbA1c from baseline to endpoint (Week 26).
Outcome measures
| Measure |
Exenatide Once Weekly
n=214 Participants
Subcutaneous injection, 2.0mg, once a week.
|
Insulin Glargine
n=212 Participants
Subcutaneous injection, titrated to achieve fasting serum glucose target, once a day
|
|---|---|---|
|
Change in HbA1c From Baseline to Endpoint (Week 26)
|
-1.11 percentage of total hemoglobin
Standard Error 0.06
|
-0.68 percentage of total hemoglobin
Standard Error 0.06
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: FAS Population. Only subjects with baseline HbA1c \> target were included in calculation. Missing data at endpoint was imputed using LOCF approach.
Percentage of subjects achieving HbA1c \<=7.0% (for subjects with HbA1c \>7% at baseline)
Outcome measures
| Measure |
Exenatide Once Weekly
n=211 Participants
Subcutaneous injection, 2.0mg, once a week.
|
Insulin Glargine
n=210 Participants
Subcutaneous injection, titrated to achieve fasting serum glucose target, once a day
|
|---|---|---|
|
Percentage of Subjects Achieving HbA1c<=7%
|
42.2 percentage of subjects
|
21.0 percentage of subjects
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: FAS Population. Only subjects with baseline HbA1c \> target were included in calculation. Missing data at endpoint was imputed using LOCF approach.
Percentage of subjects achieving HbA1c \<=6.5% (for subjects with HbA1c \>6.5% at baseline)
Outcome measures
| Measure |
Exenatide Once Weekly
n=214 Participants
Subcutaneous injection, 2.0mg, once a week.
|
Insulin Glargine
n=212 Participants
Subcutaneous injection, titrated to achieve fasting serum glucose target, once a day
|
|---|---|---|
|
Percentage of Subjects Achieving HbA1c<=6.5%
|
20.6 percentage of subjects
|
4.2 percentage of subjects
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: FAS Population. Missing data at endpoint was imputed using LOCF approach.
Change in FSG (centralized measurement) from baseline to endpoint (Week 26)
Outcome measures
| Measure |
Exenatide Once Weekly
n=212 Participants
Subcutaneous injection, 2.0mg, once a week.
|
Insulin Glargine
n=211 Participants
Subcutaneous injection, titrated to achieve fasting serum glucose target, once a day
|
|---|---|---|
|
Change in Fasting Serum Glucose (FSG) From Baseline to Endpoint (Week 26)
|
-46.09 mg/dL
Standard Error 2.40
|
-40.82 mg/dL
Standard Error 2.39
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: FAS Population. Missing data at endpoint was imputed using LOCF approach.
Change in Body Weight from baseline to endpoint (Week 26)
Outcome measures
| Measure |
Exenatide Once Weekly
n=214 Participants
Subcutaneous injection, 2.0mg, once a week.
|
Insulin Glargine
n=212 Participants
Subcutaneous injection, titrated to achieve fasting serum glucose target, once a day
|
|---|---|---|
|
Change in Body Weight From Baseline to Endpoint (Week 26)
|
-1.67 kg
Standard Error 0.17
|
0.34 kg
Standard Error 0.17
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: FAS Population. Missing data at endpoint was imputed using LOCF approach.
Change in Total Cholesterol from baseline to endpoint (Week 26)
Outcome measures
| Measure |
Exenatide Once Weekly
n=213 Participants
Subcutaneous injection, 2.0mg, once a week.
|
Insulin Glargine
n=212 Participants
Subcutaneous injection, titrated to achieve fasting serum glucose target, once a day
|
|---|---|---|
|
Change in Total Cholesterol From Baseline to Endpoint (Week 26)
|
-14.21 mg/dL
Standard Error 1.67
|
-6.32 mg/dL
Standard Error 1.67
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: FAS Population. Missing data at endpoint was imputed using LOCF approach.
Change in HDL-C from baseline to endpoint (Week 26)
Outcome measures
| Measure |
Exenatide Once Weekly
n=213 Participants
Subcutaneous injection, 2.0mg, once a week.
|
Insulin Glargine
n=212 Participants
Subcutaneous injection, titrated to achieve fasting serum glucose target, once a day
|
|---|---|---|
|
Change in High-density Lipoprotein Cholesterol (HDL-C) From Baseline to Endpoint (Week 26)
|
-0.99 mg/dL
Standard Error 0.52
|
-0.71 mg/dL
Standard Error 0.51
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: FAS Population. Missing data at endpoint was imputed using LOCF approach.
Ratio of Triglycerides (measured in mg/dL) at endpoint (Week 26) to Baseline. Log(Postbaseline Triglycerides) - log(Baseline Triglycerides); change from baseline to endpoint is presented as ratio of endpoint to baseline.
Outcome measures
| Measure |
Exenatide Once Weekly
n=213 Participants
Subcutaneous injection, 2.0mg, once a week.
|
Insulin Glargine
n=212 Participants
Subcutaneous injection, titrated to achieve fasting serum glucose target, once a day
|
|---|---|---|
|
Ratio of Fasting Triglycerides at Endpoint (Week 26) to Baseline
|
1.00 ratio
Standard Error 1.02
|
1.00 ratio
Standard Error 1.02
|
SECONDARY outcome
Timeframe: Baseline, Week 26Population: FAS Population. Missing data at endpoint was imputed using LOCF approach.
Change in Blood Pressure from baseline to endpoint (Week 26)
Outcome measures
| Measure |
Exenatide Once Weekly
n=214 Participants
Subcutaneous injection, 2.0mg, once a week.
|
Insulin Glargine
n=212 Participants
Subcutaneous injection, titrated to achieve fasting serum glucose target, once a day
|
|---|---|---|
|
Change in Blood Pressure From Baseline to Endpoint (Week 26)
Systolic Blood Pressure
|
-4.5 mmHg
Standard Deviation 14.04
|
-2.6 mmHg
Standard Deviation 14.29
|
|
Change in Blood Pressure From Baseline to Endpoint (Week 26)
Diastolic Blood Pressure
|
-1.1 mmHg
Standard Deviation 9.25
|
-2.5 mmHg
Standard Deviation 8.88
|
SECONDARY outcome
Timeframe: Baseline to Week 26Population: FAS Population.
Major confirmed hypoglycemia was defined as (1) any event accompanying symptoms consistent with hypoglycemia that resulted in loss of consciousness or seizure but resolved promptly in response to administration of glucagon or (2) glucose, or documented hypoglycemia (blood glucose \<3.0 mmol/L \[54 mg/dL\]) requiring assistance because of severe impairment in consciousness or motor activity whether or not symptoms of hypoglycemia were felt by the patient. 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 postbaseline visit date - baseline visit date. Mean and SE were then derived from FAS.
Outcome measures
| Measure |
Exenatide Once Weekly
n=215 Participants
Subcutaneous injection, 2.0mg, once a week.
|
Insulin Glargine
n=212 Participants
Subcutaneous injection, titrated to achieve fasting serum glucose target, once a day
|
|---|---|---|
|
Assessment on Event Rate of Treatment-emergent Major Hypoglycemic Events
|
0.00 events per subject-year
Standard Error 0.00
|
0.00 events per subject-year
Standard Error 0.00
|
SECONDARY outcome
Timeframe: Baseline to Week 26Population: FAS Population.
Minor confirmed hypoglycemia was defined as any event a patient felt that he or she was experiencing a sign or symptom associated with hypoglycemia that resolved by self-treatment or on its own, and a concurrent self-monitoring fingerstick 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 postbaseline visit date - baseline visit date. Mean and SE were then derived from FAS.
Outcome measures
| Measure |
Exenatide Once Weekly
n=215 Participants
Subcutaneous injection, 2.0mg, once a week.
|
Insulin Glargine
n=212 Participants
Subcutaneous injection, titrated to achieve fasting serum glucose target, once a day
|
|---|---|---|
|
Assessment on Event Rate of Treatment-emergent Minor Hypoglycemic Events
|
0.01 events per subject-year
Standard Error 0.01
|
0.16 events per subject-year
Standard Error 0.13
|
Adverse Events
Exenatide Once Weekly
Insulin Glargine
Serious adverse events
| Measure |
Exenatide Once Weekly
n=215 participants at risk
Subcutaneous injection, 2.0mg, once a week.
|
Insulin Glargine
n=212 participants at risk
Subcutaneous injection, titrated to achieve fasting serum glucose target, once a day
|
|---|---|---|
|
Cardiac disorders
Atrial fibrillation
|
0.47%
1/215
|
0.00%
0/212
|
|
Cardiac disorders
Cardiac failure
|
0.47%
1/215
|
0.00%
0/212
|
|
Injury, poisoning and procedural complications
Fibula fracture
|
0.47%
1/215
|
0.00%
0/212
|
|
Hepatobiliary disorders
Jaundice cholestatic
|
0.47%
1/215
|
0.00%
0/212
|
|
Nervous system disorders
Lacunar infarction
|
0.47%
1/215
|
0.00%
0/212
|
|
Respiratory, thoracic and mediastinal disorders
Status asthmaticus
|
0.47%
1/215
|
0.00%
0/212
|
|
Injury, poisoning and procedural complications
Tibia fracture
|
0.47%
1/215
|
0.00%
0/212
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/215
|
0.47%
1/212
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.00%
0/215
|
0.47%
1/212
|
|
Gastrointestinal disorders
Diverticulitis intestinal haemorrhagic
|
0.00%
0/215
|
0.47%
1/212
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/215
|
0.47%
1/212
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/215
|
0.47%
1/212
|
Other adverse events
| Measure |
Exenatide Once Weekly
n=215 participants at risk
Subcutaneous injection, 2.0mg, once a week.
|
Insulin Glargine
n=212 participants at risk
Subcutaneous injection, titrated to achieve fasting serum glucose target, once a day
|
|---|---|---|
|
General disorders
Injection site induration
|
27.0%
58/215
|
1.4%
3/212
|
|
Infections and infestations
Nasopharyngitis
|
25.6%
55/215
|
21.2%
45/212
|
|
Gastrointestinal disorders
Nausea
|
12.6%
27/215
|
2.8%
6/212
|
|
Gastrointestinal disorders
Constipation
|
11.2%
24/215
|
3.3%
7/212
|
|
Gastrointestinal disorders
Diarrhoea
|
8.8%
19/215
|
2.4%
5/212
|
|
General disorders
Induration
|
8.4%
18/215
|
0.00%
0/212
|
|
Gastrointestinal disorders
Vomiting
|
8.4%
18/215
|
2.4%
5/212
|
|
General disorders
Injection site pruritus
|
6.5%
14/215
|
0.00%
0/212
|
|
Gastrointestinal disorders
Abdominal discomfort
|
5.1%
11/215
|
0.94%
2/212
|
|
Metabolism and nutrition disorders
Decreased appetite
|
5.1%
11/215
|
0.47%
1/212
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60