Trial Outcomes & Findings for A Study to Compare the Glycemic Effects, Safety, and Tolerability of Exenatide Once Weekly to Those of Sitagliptin and Pioglitazone,in Subjects With Type 2 Diabetes Treated With Metformin (DURATION - 2) (NCT NCT00637273)
NCT ID: NCT00637273
Last Updated: 2015-04-07
Results Overview
Absolute change in HbA1c from baseline (Day 1) to Week 26 \[Week 26 - Baseline\].
COMPLETED
PHASE3
514 participants
Day 1, Week 26
2015-04-07
Participant Flow
Participant milestones
| Measure |
Exenatide Once Weekly
Exenatide once weekly 2 mg subcutaneous weekly plus placebo oral once daily in the morning
|
Sitagliptin
Sitagliptin 100 mg oral once daily in the morning plus placebo once weekly subcutaneous weekly
|
Pioglitazone
Pioglitazone 45 mg oral once daily in the morning plus placebo once weekly subcutaneous weekly
|
|---|---|---|---|
|
Overall Study
STARTED
|
170
|
172
|
172
|
|
Overall Study
Intent to Treat (ITT)
|
160
|
166
|
165
|
|
Overall Study
COMPLETED
|
127
|
144
|
131
|
|
Overall Study
NOT COMPLETED
|
43
|
28
|
41
|
Reasons for withdrawal
| Measure |
Exenatide Once Weekly
Exenatide once weekly 2 mg subcutaneous weekly plus placebo oral once daily in the morning
|
Sitagliptin
Sitagliptin 100 mg oral once daily in the morning plus placebo once weekly subcutaneous weekly
|
Pioglitazone
Pioglitazone 45 mg oral once daily in the morning plus placebo once weekly subcutaneous weekly
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
11
|
5
|
7
|
|
Overall Study
Lost to Follow-up
|
8
|
9
|
13
|
|
Overall Study
Protocol Violation
|
2
|
4
|
1
|
|
Overall Study
Withdrawal of Consent
|
18
|
6
|
18
|
|
Overall Study
Investigator Decision
|
1
|
3
|
1
|
|
Overall Study
Administrative
|
2
|
0
|
0
|
|
Overall Study
Loss of Glucose Control
|
1
|
1
|
1
|
Baseline Characteristics
A Study to Compare the Glycemic Effects, Safety, and Tolerability of Exenatide Once Weekly to Those of Sitagliptin and Pioglitazone,in Subjects With Type 2 Diabetes Treated With Metformin (DURATION - 2)
Baseline characteristics by cohort
| Measure |
Exenatide Once Weekly
n=160 Participants
Exenatide once weekly 2 mg subcutaneous weekly plus placebo oral once daily in the morning
|
Sitagliptin
n=166 Participants
Sitagliptin 100 mg oral once daily in the morning plus placebo once weekly subcutaneous weekly
|
Pioglitazone
n=165 Participants
Pioglitazone 45 mg oral once daily in the morning plus placebo once weekly subcutaneous weekly
|
Total
n=491 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
|
0 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
140 Participants
n=5 Participants
|
149 Participants
n=7 Participants
|
143 Participants
n=5 Participants
|
432 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
20 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
59 Participants
n=4 Participants
|
|
Age, Continuous
|
52.4 years
STANDARD_DEVIATION 10.41 • n=5 Participants
|
52.2 years
STANDARD_DEVIATION 10.54 • n=7 Participants
|
53.0 years
STANDARD_DEVIATION 9.92 • n=5 Participants
|
52.5 years
STANDARD_DEVIATION 10.28 • n=4 Participants
|
|
Sex: Female, Male
Female
|
71 Participants
n=5 Participants
|
80 Participants
n=7 Participants
|
86 Participants
n=5 Participants
|
237 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
89 Participants
n=5 Participants
|
86 Participants
n=7 Participants
|
79 Participants
n=5 Participants
|
254 Participants
n=4 Participants
|
|
Glycosylated hemoglobin (HbA1c)
|
8.6 percentage of total hemoglobin
STANDARD_DEVIATION 1.20 • n=5 Participants
|
8.5 percentage of total hemoglobin
STANDARD_DEVIATION 1.17 • n=7 Participants
|
8.5 percentage of total hemoglobin
STANDARD_DEVIATION 1.08 • n=5 Participants
|
8.5 percentage of total hemoglobin
STANDARD_DEVIATION 1.15 • n=4 Participants
|
|
Weight
|
89.1 kg
STANDARD_DEVIATION 19.55 • n=5 Participants
|
87.0 kg
STANDARD_DEVIATION 20.25 • n=7 Participants
|
87.9 kg
STANDARD_DEVIATION 20.49 • n=5 Participants
|
88.0 kg
STANDARD_DEVIATION 20.08 • n=4 Participants
|
PRIMARY outcome
Timeframe: Day 1, Week 26Population: The ITT Population included randomized subjects who received at least one injection of study medication. Missing data up to Week 26 were imputed using the last observation carried forward (LOCF) approach for subjects who had data for at least one scheduled visit (including Early Termination) subsequent to the baseline measurement.
Absolute change in HbA1c from baseline (Day 1) to Week 26 \[Week 26 - Baseline\].
Outcome measures
| Measure |
Exenatide Once Weekly
n=159 Participants
Exenatide once weekly 2 mg subcutaneous weekly plus placebo oral once daily in the morning
|
Sitagliptin
n=162 Participants
Sitagliptin 100 mg oral once daily in the morning plus placebo once weekly subcutaneous weekly
|
Pioglitazone
n=160 Participants
Pioglitazone 45 mg oral once daily in the morning plus placebo once weekly subcutaneous weekly
|
|---|---|---|---|
|
Change in HbA1c From Baseline to Week 26
|
-1.55 percentage of total hemoglobin
Standard Error 0.100
|
-0.92 percentage of total hemoglobin
Standard Error 0.099
|
-1.23 percentage of total hemoglobin
Standard Error 0.099
|
SECONDARY outcome
Timeframe: Week 26Population: ITT Population. Missing data up to Week 26 were imputed using LOCF approach for subjects who had data for at least one scheduled visit (including Early Termination) subsequent to the baseline measurement. Subjects without post-baseline HbA1c measurement were categorized as not achieving goal.
Percentages of subjects achieving HbA1c target values of \<7% at Week 26.
Outcome measures
| Measure |
Exenatide Once Weekly
n=160 Participants
Exenatide once weekly 2 mg subcutaneous weekly plus placebo oral once daily in the morning
|
Sitagliptin
n=166 Participants
Sitagliptin 100 mg oral once daily in the morning plus placebo once weekly subcutaneous weekly
|
Pioglitazone
n=165 Participants
Pioglitazone 45 mg oral once daily in the morning plus placebo once weekly subcutaneous weekly
|
|---|---|---|---|
|
Percentage of Subjects Achieving HbA1c Target of <7% at Week 26
|
58.8 percentage of subjects
|
30.7 percentage of subjects
|
43.6 percentage of subjects
|
SECONDARY outcome
Timeframe: Week 26Population: ITT Population. Missing data up to Week 26 were imputed using LOCF approach for subjects who had data for at least one scheduled visit (including Early Termination) subsequent to the baseline measurement. Subjects without post-baseline HbA1c measurement were categorized as not achieving goal.
Percentages of subjects achieving HbA1c target values of \<=6.5% at Week 26.
Outcome measures
| Measure |
Exenatide Once Weekly
n=160 Participants
Exenatide once weekly 2 mg subcutaneous weekly plus placebo oral once daily in the morning
|
Sitagliptin
n=166 Participants
Sitagliptin 100 mg oral once daily in the morning plus placebo once weekly subcutaneous weekly
|
Pioglitazone
n=165 Participants
Pioglitazone 45 mg oral once daily in the morning plus placebo once weekly subcutaneous weekly
|
|---|---|---|---|
|
Percentage of Subjects Achieving HbA1c Target of <=6.5% at Week 26
|
38.8 percentage of subjects
|
15.7 percentage of subjects
|
26.7 percentage of subjects
|
SECONDARY outcome
Timeframe: Week 26Population: ITT Population. Missing data up to Week 26 were imputed using LOCF approach for subjects who had data for at least one scheduled visit (including Early Termination) subsequent to the baseline measurement. Subjects without post-baseline HbA1c measurement were categorized as not achieving goal.
Percentages of subjects achieving HbA1c target values of \<=6.0% at Week 26.
Outcome measures
| Measure |
Exenatide Once Weekly
n=160 Participants
Exenatide once weekly 2 mg subcutaneous weekly plus placebo oral once daily in the morning
|
Sitagliptin
n=166 Participants
Sitagliptin 100 mg oral once daily in the morning plus placebo once weekly subcutaneous weekly
|
Pioglitazone
n=165 Participants
Pioglitazone 45 mg oral once daily in the morning plus placebo once weekly subcutaneous weekly
|
|---|---|---|---|
|
Percentage of Subjects Achieving HbA1c Target of <=6.0% at Week 26
|
13.8 percentage of subjects
|
9.0 percentage of subjects
|
4.8 percentage of subjects
|
SECONDARY outcome
Timeframe: Day 1, Week 26Population: ITT Population. Missing data up to Week 26 were imputed using the LOCF approach for subjects who had data for at least one scheduled visit (including Early Termination) subsequent to the baseline measurement.
Change in body weight from baseline (Day 1) to Week 26.
Outcome measures
| Measure |
Exenatide Once Weekly
n=160 Participants
Exenatide once weekly 2 mg subcutaneous weekly plus placebo oral once daily in the morning
|
Sitagliptin
n=163 Participants
Sitagliptin 100 mg oral once daily in the morning plus placebo once weekly subcutaneous weekly
|
Pioglitazone
n=165 Participants
Pioglitazone 45 mg oral once daily in the morning plus placebo once weekly subcutaneous weekly
|
|---|---|---|---|
|
Change in Body Weight From Baseline to Week 26
|
-2.31 kg
Standard Error 0.323
|
-0.77 kg
Standard Error 0.322
|
2.79 kg
Standard Error 0.320
|
SECONDARY outcome
Timeframe: Day 1, Week 26Population: ITT Population. Missing data up to Week 26 were imputed using the LOCF approach for subjects who had data for at least one scheduled visit (including Early Termination) subsequent to the baseline measurement.
Change in fasting plasma glucose from baseline (Day 1) to Week 26.
Outcome measures
| Measure |
Exenatide Once Weekly
n=155 Participants
Exenatide once weekly 2 mg subcutaneous weekly plus placebo oral once daily in the morning
|
Sitagliptin
n=161 Participants
Sitagliptin 100 mg oral once daily in the morning plus placebo once weekly subcutaneous weekly
|
Pioglitazone
n=158 Participants
Pioglitazone 45 mg oral once daily in the morning plus placebo once weekly subcutaneous weekly
|
|---|---|---|---|
|
Change in Fasting Plasma Glucose From Baseline to Week 26
|
-31.8 mg/dL
Standard Error 3.79
|
-16.3 mg/dL
Standard Error 3.72
|
-27.3 mg/dL
Standard Error 3.75
|
SECONDARY outcome
Timeframe: Day 1, Week 26Population: ITT Population. Missing data up to Week 26 were imputed using the LOCF approach for subjects who had data for at least one scheduled visit (including Early Termination) subsequent to the baseline measurement.
Change in systolic blood pressure from baseline (Day 1) to Week 26.
Outcome measures
| Measure |
Exenatide Once Weekly
n=160 Participants
Exenatide once weekly 2 mg subcutaneous weekly plus placebo oral once daily in the morning
|
Sitagliptin
n=163 Participants
Sitagliptin 100 mg oral once daily in the morning plus placebo once weekly subcutaneous weekly
|
Pioglitazone
n=165 Participants
Pioglitazone 45 mg oral once daily in the morning plus placebo once weekly subcutaneous weekly
|
|---|---|---|---|
|
Change in Systolic Blood Pressure From Baseline to Week 26
|
-3.6 mmHg
Standard Error 0.97
|
0.2 mmHg
Standard Error 0.95
|
-1.6 mmHg
Standard Error 0.95
|
SECONDARY outcome
Timeframe: Day 1, Week 26Population: ITT Population. Missing data up to Week 26 were imputed using the LOCF approach for subjects who had data for at least one scheduled visit (including Early Termination) subsequent to the baseline measurement.
Change in diastolic blood pressure from baseline (Day 1) to Week 26.
Outcome measures
| Measure |
Exenatide Once Weekly
n=160 Participants
Exenatide once weekly 2 mg subcutaneous weekly plus placebo oral once daily in the morning
|
Sitagliptin
n=163 Participants
Sitagliptin 100 mg oral once daily in the morning plus placebo once weekly subcutaneous weekly
|
Pioglitazone
n=165 Participants
Pioglitazone 45 mg oral once daily in the morning plus placebo once weekly subcutaneous weekly
|
|---|---|---|---|
|
Change in Diastolic Blood Pressure From Baseline to Week 26
|
-1.4 mmHg
Standard Error 0.57
|
-0.4 mmHg
Standard Error 0.57
|
-2.5 mmHg
Standard Error 0.56
|
SECONDARY outcome
Timeframe: Day 1, Week 26Population: ITT Population. Missing data up to Week 26 were imputed using the LOCF approach for subjects who had data for at least one scheduled visit (including Early Termination) subsequent to the baseline measurement.
Change in fasting total cholesterol from baseline (Day 1) to Week 26.
Outcome measures
| Measure |
Exenatide Once Weekly
n=146 Participants
Exenatide once weekly 2 mg subcutaneous weekly plus placebo oral once daily in the morning
|
Sitagliptin
n=147 Participants
Sitagliptin 100 mg oral once daily in the morning plus placebo once weekly subcutaneous weekly
|
Pioglitazone
n=154 Participants
Pioglitazone 45 mg oral once daily in the morning plus placebo once weekly subcutaneous weekly
|
|---|---|---|---|
|
Change in Fasting Total Cholesterol From Baseline to Week 26
|
-0.6 mg/dL
Standard Error 2.51
|
3.1 mg/dL
Standard Error 2.49
|
6.2 mg/dL
Standard Error 2.46
|
SECONDARY outcome
Timeframe: Day 1, Week 26Population: ITT Population. Missing data up to Week 26 were imputed using the LOCF approach for subjects who had data for at least one scheduled visit (including Early Termination) subsequent to the baseline measurement.
Change in fasting HDL from baseline (Day 1) to Week 26.
Outcome measures
| Measure |
Exenatide Once Weekly
n=146 Participants
Exenatide once weekly 2 mg subcutaneous weekly plus placebo oral once daily in the morning
|
Sitagliptin
n=147 Participants
Sitagliptin 100 mg oral once daily in the morning plus placebo once weekly subcutaneous weekly
|
Pioglitazone
n=154 Participants
Pioglitazone 45 mg oral once daily in the morning plus placebo once weekly subcutaneous weekly
|
|---|---|---|---|
|
Change in Fasting High-density Lipoprotein (HDL) From Baseline to Week 26
|
2.0 mg/dL
Standard Error 0.61
|
2.0 mg/dL
Standard Error 0.60
|
6.2 mg/dL
Standard Error 0.59
|
SECONDARY outcome
Timeframe: Day 1, Week 26Population: ITT Population. Missing data up to Week 26 were imputed using the LOCF approach for subjects who had data for at least one scheduled visit (including Early Termination) subsequent to the baseline measurement.
Ratio of triglycerides (measured in mg/dL) at Week 26 to baseline (Day 1). 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=159 Participants
Exenatide once weekly 2 mg subcutaneous weekly plus placebo oral once daily in the morning
|
Sitagliptin
n=161 Participants
Sitagliptin 100 mg oral once daily in the morning plus placebo once weekly subcutaneous weekly
|
Pioglitazone
n=159 Participants
Pioglitazone 45 mg oral once daily in the morning plus placebo once weekly subcutaneous weekly
|
|---|---|---|---|
|
Ratio of Fasting Triglycerides at Week 26 to Baseline
|
0.95 ratio
Standard Error 0.029
|
0.95 ratio
Standard Error 0.028
|
0.84 ratio
Standard Error 0.025
|
SECONDARY outcome
Timeframe: Day 1 to Week 26Population: ITT Population.
Major hypoglycemia: events that, in the judgment of the investigator or physician, resulted in loss of consciousness, seizure, coma, or other change in mental status consistent with neuroglycopenia, in which symptoms resolved after administration of intramuscular glucagon or intravenous glucose, required third-party assistance, and was accompanied by a blood glucose concentration \< 54 mg/dL prior to treatment. Minor hypoglycemia: symptoms consistent with hypoglycemia and blood glucose concentration \< 54 mg/dL prior to treatment and not classified as major hypoglycemia.
Outcome measures
| Measure |
Exenatide Once Weekly
n=160 Participants
Exenatide once weekly 2 mg subcutaneous weekly plus placebo oral once daily in the morning
|
Sitagliptin
n=166 Participants
Sitagliptin 100 mg oral once daily in the morning plus placebo once weekly subcutaneous weekly
|
Pioglitazone
n=165 Participants
Pioglitazone 45 mg oral once daily in the morning plus placebo once weekly subcutaneous weekly
|
|---|---|---|---|
|
Assessment on Event Rate of Treatment-emergent Hypoglycemic Events
Treatment-Emergent Minor Hypoglycemia
|
0.03 rate per subject-year
Standard Error 0.021
|
0.12 rate per subject-year
Standard Error 0.039
|
0.01 rate per subject-year
Standard Error 0.014
|
|
Assessment on Event Rate of Treatment-emergent Hypoglycemic Events
Treatment-Emergent Major Hypoglycemia
|
0.00 rate per subject-year
Standard Error 0.000
|
0.00 rate per subject-year
Standard Error 0.000
|
0.00 rate per subject-year
Standard Error 0.00
|
Adverse Events
Exenatide Once Weekly
Sitagliptin
Pioglitazone
Serious adverse events
| Measure |
Exenatide Once Weekly
n=160 participants at risk
Exenatide once weekly 2 mg subcutaneous weekly plus placebo oral once daily in the morning
|
Sitagliptin
n=166 participants at risk
Sitagliptin 100 mg oral once daily in the morning plus placebo once weekly subcutaneous weekly
|
Pioglitazone
n=165 participants at risk
Pioglitazone 45 mg oral once daily in the morning plus placebo once weekly subcutaneous weekly
|
|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Cryptogenic organising pneumonia
|
0.62%
1/160
|
0.00%
0/166
|
0.00%
0/165
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.62%
1/160
|
0.00%
0/166
|
0.00%
0/165
|
|
Injury, poisoning and procedural complications
Postoperative wound complication
|
0.62%
1/160
|
0.00%
0/166
|
0.00%
0/165
|
|
Infections and infestations
Viral pericarditis
|
0.62%
1/160
|
0.00%
0/166
|
0.00%
0/165
|
|
Cardiac disorders
Angina unstable
|
0.00%
0/160
|
0.00%
0/166
|
0.61%
1/165
|
|
Infections and infestations
Bacterial pyelonephritis
|
0.00%
0/160
|
0.60%
1/166
|
0.00%
0/165
|
|
Hepatobiliary disorders
Bile duct obstruction
|
0.00%
0/160
|
0.00%
0/166
|
0.61%
1/165
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/160
|
0.60%
1/166
|
0.61%
1/165
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/160
|
0.00%
0/166
|
0.61%
1/165
|
|
Infections and infestations
Clostridial infection
|
0.00%
0/160
|
0.00%
0/166
|
0.61%
1/165
|
|
Cardiac disorders
Coronary artery occlusion
|
0.00%
0/160
|
0.00%
0/166
|
1.2%
2/165
|
|
Infections and infestations
Dengue fever
|
0.00%
0/160
|
0.00%
0/166
|
0.61%
1/165
|
|
Infections and infestations
Escherichia bacteraemia
|
0.00%
0/160
|
0.60%
1/166
|
0.00%
0/165
|
|
Vascular disorders
Hypertension
|
0.00%
0/160
|
0.60%
1/166
|
0.00%
0/165
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/160
|
0.60%
1/166
|
0.61%
1/165
|
|
Infections and infestations
Pancreatic abscess
|
0.00%
0/160
|
0.00%
0/166
|
0.61%
1/165
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/160
|
0.00%
0/166
|
0.61%
1/165
|
|
Gastrointestinal disorders
Pancreatitis necrotising
|
0.00%
0/160
|
0.00%
0/166
|
0.61%
1/165
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Papillary thyroid cancer
|
0.00%
0/160
|
0.60%
1/166
|
0.00%
0/165
|
|
Renal and urinary disorders
Renal failure acute
|
0.00%
0/160
|
0.00%
0/166
|
0.61%
1/165
|
|
Infections and infestations
Sepsis
|
0.00%
0/160
|
0.00%
0/166
|
0.61%
1/165
|
|
Infections and infestations
Viral infection
|
0.00%
0/160
|
0.00%
0/166
|
0.61%
1/165
|
|
Infections and infestations
Wound infection staphylococcal
|
0.00%
0/160
|
0.00%
0/166
|
0.61%
1/165
|
Other adverse events
| Measure |
Exenatide Once Weekly
n=160 participants at risk
Exenatide once weekly 2 mg subcutaneous weekly plus placebo oral once daily in the morning
|
Sitagliptin
n=166 participants at risk
Sitagliptin 100 mg oral once daily in the morning plus placebo once weekly subcutaneous weekly
|
Pioglitazone
n=165 participants at risk
Pioglitazone 45 mg oral once daily in the morning plus placebo once weekly subcutaneous weekly
|
|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
23.8%
38/160
|
9.6%
16/166
|
4.8%
8/165
|
|
Gastrointestinal disorders
Diarrhoea
|
18.1%
29/160
|
9.6%
16/166
|
7.3%
12/165
|
|
Gastrointestinal disorders
Vomiting
|
11.2%
18/160
|
2.4%
4/166
|
3.0%
5/165
|
|
Nervous system disorders
Headache
|
9.4%
15/160
|
9.0%
15/166
|
4.2%
7/165
|
|
Infections and infestations
Urinary tract infection
|
6.2%
10/160
|
5.4%
9/166
|
3.6%
6/165
|
|
Gastrointestinal disorders
Constipation
|
5.6%
9/160
|
1.8%
3/166
|
1.2%
2/165
|
|
General disorders
Fatigue
|
5.6%
9/160
|
0.00%
0/166
|
3.0%
5/165
|
|
General disorders
Injection site pruritus
|
5.0%
8/160
|
4.8%
8/166
|
1.2%
2/165
|
|
Infections and infestations
Upper respiratory tract infection
|
3.8%
6/160
|
9.0%
15/166
|
10.3%
17/165
|
|
Infections and infestations
Sinusitis
|
3.1%
5/160
|
1.2%
2/166
|
6.7%
11/165
|
|
General disorders
Oedema peripheral
|
1.2%
2/160
|
3.0%
5/166
|
7.9%
13/165
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60