Trial Outcomes & Findings for Efficacy and Safety of Basal-bolus Therapy, Comparing Stepwise Addition of Insulin Aspart Versus Complete Basal-bolus Regimen (NCT NCT01165684)
NCT ID: NCT01165684
Last Updated: 2017-02-17
Results Overview
Estimated mean change from baseline in HbA1c after 32 Weeks of treatment
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
401 participants
Primary outcome timeframe
Week 0, Week 32
Results posted on
2017-02-17
Participant Flow
The trial was conducted at 69 sites in 7 countries: Argentina (7), Brazil (5), Canada (12), France (7), Macedonia (1), Slovenia (4), and the US (31). Of 12 sites in Canada, one site (Site 303) closed early on 07-Mar-2011.
Subjects on pre-trial metformin and pioglitazone continued their medication.
Participant milestones
| Measure |
Step-wise
In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
|
Basal-bolus
In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.
|
|---|---|---|
|
Overall Study
STARTED
|
201
|
200
|
|
Overall Study
Exposed
|
198
|
199
|
|
Overall Study
COMPLETED
|
173
|
148
|
|
Overall Study
NOT COMPLETED
|
28
|
52
|
Reasons for withdrawal
| Measure |
Step-wise
In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
|
Basal-bolus
In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
1
|
|
Overall Study
Lack of Efficacy
|
2
|
1
|
|
Overall Study
Protocol Violation
|
7
|
15
|
|
Overall Study
Withdrawal Criteria
|
2
|
13
|
|
Overall Study
Unclassified
|
16
|
22
|
Baseline Characteristics
Efficacy and Safety of Basal-bolus Therapy, Comparing Stepwise Addition of Insulin Aspart Versus Complete Basal-bolus Regimen
Baseline characteristics by cohort
| Measure |
Step-wise
n=201 Participants
In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
|
Basal-bolus
n=200 Participants
In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.
|
Total
n=401 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
60.0 years
STANDARD_DEVIATION 9.1 • n=5 Participants
|
59.6 years
STANDARD_DEVIATION 9.5 • n=7 Participants
|
59.8 years
STANDARD_DEVIATION 9.3 • n=5 Participants
|
|
Gender
Female
|
97 Participants
n=5 Participants
|
101 Participants
n=7 Participants
|
198 Participants
n=5 Participants
|
|
Gender
Male
|
104 Participants
n=5 Participants
|
99 Participants
n=7 Participants
|
203 Participants
n=5 Participants
|
|
Body weight
|
88.9 kg
STANDARD_DEVIATION 18.7 • n=5 Participants
|
86.1 kg
STANDARD_DEVIATION 15.2 • n=7 Participants
|
87.5 kg
STANDARD_DEVIATION 17.1 • n=5 Participants
|
|
Body Mass Index (BMI)
|
31.5 kg/m^2
STANDARD_DEVIATION 4.8 • n=5 Participants
|
30.7 kg/m^2
STANDARD_DEVIATION 4.6 • n=7 Participants
|
31.1 kg/m^2
STANDARD_DEVIATION 4.7 • n=5 Participants
|
|
Glycosylated haemoglobin (HbA1c)
|
7.9 percentage of glycosylated haemoglobin
STANDARD_DEVIATION 0.6 • n=5 Participants
|
7.9 percentage of glycosylated haemoglobin
STANDARD_DEVIATION 0.6 • n=7 Participants
|
7.9 percentage of glycosylated haemoglobin
STANDARD_DEVIATION 0.6 • n=5 Participants
|
|
Fasting plasma glucose (FPG)
|
7.0 mmol/L
STANDARD_DEVIATION 1.9 • n=5 Participants
|
6.9 mmol/L
STANDARD_DEVIATION 1.6 • n=7 Participants
|
6.9 mmol/L
STANDARD_DEVIATION 1.8 • n=5 Participants
|
PRIMARY outcome
Timeframe: Week 0, Week 32Population: Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 383 subjects contributed to the statistical analysis at Week 32.
Estimated mean change from baseline in HbA1c after 32 Weeks of treatment
Outcome measures
| Measure |
Step-wise
n=195 Participants
In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
|
Basal-bolus
n=188 Participants
In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.
|
|---|---|---|
|
Change in Glycosylated Haemoglobin (HbA1c) From Baseline to Week 32
|
-0.98 percentage of glycosylated haemoglobin
Standard Error 0.06
|
-1.12 percentage of glycosylated haemoglobin
Standard Error 0.06
|
SECONDARY outcome
Timeframe: Week 0, Week 10Population: Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 376 subjects contributed to the statistical analysis at Week 10.
Estimated mean change from baseline in HbA1c after 10 Weeks of treatment
Outcome measures
| Measure |
Step-wise
n=193 Participants
In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
|
Basal-bolus
n=183 Participants
In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.
|
|---|---|---|
|
Change in Glycosylated Haemoglobin (HbA1c) From Baseline to Week 10
|
-0.45 percentage of glycosylated haemoglobin
Standard Error 0.05
|
-1.00 percentage of glycosylated haemoglobin
Standard Error 0.05
|
SECONDARY outcome
Timeframe: Week 0, Week 21Population: Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 383 subjects contributed to the statistical analysis at Week 21.
Estimated mean change from baseline in HbA1c after 21 Weeks of treatment
Outcome measures
| Measure |
Step-wise
n=195 Participants
In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
|
Basal-bolus
n=188 Participants
In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.
|
|---|---|---|
|
Change in Glycosylated Haemoglobin (HbA1c) From Baseline to Week 21
|
-0.78 percentage of glycosylated haemoglobin
Standard Error 0.06
|
-1.15 percentage of glycosylated haemoglobin
Standard Error 0.06
|
SECONDARY outcome
Timeframe: Week 10Population: Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 376 subjects contributed to the statistical analysis at Week 10.
Proportion of subjects reaching HbA1c below 7.0% at Week 10
Outcome measures
| Measure |
Step-wise
n=193 Participants
In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
|
Basal-bolus
n=183 Participants
In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.
|
|---|---|---|
|
Proportion of Subjects Reaching Glycosylated Haemoglobin (HbA1c) Below 7.0% at Week 10
|
19.2 percentage (%) of subjects
|
56.3 percentage (%) of subjects
|
SECONDARY outcome
Timeframe: Week 21Population: Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 383 subjects contributed to the statistical analysis at Week 21.
Proportion of subjects reaching HbA1c below 7.0% at Week 21
Outcome measures
| Measure |
Step-wise
n=195 Participants
In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
|
Basal-bolus
n=188 Participants
In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.
|
|---|---|---|
|
Proportion of Subjects Reaching Glycosylated Haemoglobin (HbA1c) Below 7.0% at Week 21
|
45.1 percentage (%) of subjects
|
65.4 percentage (%) of subjects
|
SECONDARY outcome
Timeframe: Week 32Population: Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 383 subjects contributed to the statistical analysis at Week 32.
Proportion of subjects reaching HbA1c below 7.0% at Week 32
Outcome measures
| Measure |
Step-wise
n=195 Participants
In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
|
Basal-bolus
n=188 Participants
In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.
|
|---|---|---|
|
Proportion of Subjects Reaching Glycosylated Haemoglobin (HbA1c) Below 7.0% at Week 32
|
55.9 percentage (%) of subjects
|
63.3 percentage (%) of subjects
|
SECONDARY outcome
Timeframe: Week 10Population: Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 368 subjects contributed to data at Week 10.
Mean FPG at Week 10
Outcome measures
| Measure |
Step-wise
n=186 Participants
In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
|
Basal-bolus
n=182 Participants
In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.
|
|---|---|---|
|
Fasting Plasma Glucose (FPG) at Week 10
|
7.1 mmol/L
Standard Deviation 1.9
|
6.7 mmol/L
Standard Deviation 1.9
|
SECONDARY outcome
Timeframe: Week 21Population: Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 383 subjects contributed to the data at Week 21.
Mean FPG at Week 21
Outcome measures
| Measure |
Step-wise
n=195 Participants
In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
|
Basal-bolus
n=188 Participants
In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.
|
|---|---|---|
|
Fasting Plasma Glucose (FPG) at Week 21
|
7.1 mmol/L
Standard Deviation 2.3
|
7.0 mmol/L
Standard Deviation 2.3
|
SECONDARY outcome
Timeframe: Week 32Population: Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 383 subjects contributed to the statistical analysis at Week 32.
Estimated Mean FPG at Week 32
Outcome measures
| Measure |
Step-wise
n=195 Participants
In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
|
Basal-bolus
n=188 Participants
In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.
|
|---|---|---|
|
Fasting Plasma Glucose (FPG) at Week 32
|
7.12 mmol/L
Standard Error 0.17
|
7.01 mmol/L
Standard Error 0.17
|
SECONDARY outcome
Timeframe: Week 10Population: Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 326 subjects contributed to the data at Week 10.
Mean plasma glucose increment over 3 meals (breakfast, lunch and dinner) at Week 10
Outcome measures
| Measure |
Step-wise
n=165 Participants
In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
|
Basal-bolus
n=161 Participants
In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.
|
|---|---|---|
|
Mean Plasma Glucose Increment Over 3 Meals (Breakfast, Lunch and Dinner) at Week 10
|
2.3 mmol/L
Standard Deviation 2.2
|
1.4 mmol/L
Standard Deviation 2.0
|
SECONDARY outcome
Timeframe: Week 21Population: Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 343 subjects contributed to the data at Week 21.
Mean plasma glucose increment over 3 meals (breakfast, lunch and dinner) at Week 21
Outcome measures
| Measure |
Step-wise
n=176 Participants
In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
|
Basal-bolus
n=167 Participants
In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.
|
|---|---|---|
|
Mean Plasma Glucose Increment Over 3 Meals (Breakfast, Lunch and Dinner) at Week 21
|
1.9 mmol/L
Standard Deviation 1.8
|
1.5 mmol/L
Standard Deviation 1.8
|
SECONDARY outcome
Timeframe: Week 32Population: Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 352 subjects contributed to the statistical analysis at Week 32.
Estimated mean plasma glucose increment over 3 meals (breakfast, lunch and dinner) at Week 32
Outcome measures
| Measure |
Step-wise
n=182 Participants
In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
|
Basal-bolus
n=170 Participants
In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.
|
|---|---|---|
|
Mean Plasma Glucose Increment Over 3 Meals (Breakfast, Lunch and Dinner) at Week 32
|
1.64 mmol/L
Standard Deviation 0.12
|
1.28 mmol/L
Standard Deviation 0.13
|
SECONDARY outcome
Timeframe: Week 32Population: Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 378 subjects contributed to the statistical analysis at Week 32.
Estimated mean body weight after 32 Weeks of treatment
Outcome measures
| Measure |
Step-wise
n=190 Participants
In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
|
Basal-bolus
n=188 Participants
In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.
|
|---|---|---|
|
Body Weight at Week 32
|
89.32 kg
Standard Error 0.28
|
89.80 kg
Standard Error 0.28
|
SECONDARY outcome
Timeframe: Week 32Population: Full analysis set (FAS) included all randomised subjects and missing data were imputed using last observation carried forward (LOCF). 378 subjects contributed to the statistical analysis at Week 32.
Estimated mean BMI after 32 Weeks of treatment
Outcome measures
| Measure |
Step-wise
n=190 Participants
In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
|
Basal-bolus
n=188 Participants
In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.
|
|---|---|---|
|
Body Mass Index (BMI) at Week 32
|
31.86 kg/m^2
Standard Error 0.10
|
32.03 kg/m^2
Standard Error 0.10
|
SECONDARY outcome
Timeframe: Week 0 to Week 32Population: Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator. 397 subjects contributed with data.
A hypoglycaemic episode was defined as treatment emergent if the onset of the episode was on or after the first day of exposure to randomised treatment and no later than 1 day after the last day of randomised treatment.
Outcome measures
| Measure |
Step-wise
n=198 Participants
In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
|
Basal-bolus
n=199 Participants
In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.
|
|---|---|---|
|
Hypoglycaemic Episodes (Rate of All Treatment Emergent Hypoglycaemia Episodes)
|
33.47 Episodes /year of patient exposure
|
57.56 Episodes /year of patient exposure
|
Adverse Events
Step-wise
Serious events: 18 serious events
Other events: 40 other events
Deaths: 0 deaths
Basal-bolus
Serious events: 15 serious events
Other events: 47 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Step-wise
n=198 participants at risk
In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
|
Basal-bolus
n=199 participants at risk
In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.
|
|---|---|---|
|
Cardiac disorders
Acute myocardial infarction
|
0.00%
0/198 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
0.50%
1/199 • Number of events 1 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
|
Cardiac disorders
Atrial fibrillation
|
0.51%
1/198 • Number of events 1 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
0.00%
0/199 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
|
Cardiac disorders
Coronary artery disease
|
0.51%
1/198 • Number of events 1 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
0.00%
0/199 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
|
Cardiac disorders
Myocardial ischaemia
|
0.51%
1/198 • Number of events 1 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
0.00%
0/199 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.51%
1/198 • Number of events 1 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
0.00%
0/199 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.51%
1/198 • Number of events 1 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
0.00%
0/199 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
|
Gastrointestinal disorders
Gastrointestinal fistula
|
0.00%
0/198 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
0.50%
1/199 • Number of events 1 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.51%
1/198 • Number of events 1 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
0.00%
0/199 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
|
Gastrointestinal disorders
Pancreatitis
|
0.51%
1/198 • Number of events 1 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
0.00%
0/199 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.51%
1/198 • Number of events 1 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
0.00%
0/199 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
|
Infections and infestations
Bacterial translocation
|
0.00%
0/198 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
0.50%
1/199 • Number of events 1 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
|
Infections and infestations
Erysipelas
|
0.00%
0/198 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
0.50%
1/199 • Number of events 1 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
|
Infections and infestations
Gastroenteritis
|
0.51%
1/198 • Number of events 1 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
0.00%
0/199 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
|
Infections and infestations
Injection site infection
|
0.51%
1/198 • Number of events 1 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
0.00%
0/199 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
|
Infections and infestations
Pneumonia
|
0.51%
1/198 • Number of events 1 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
0.00%
0/199 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
|
Infections and infestations
Pyelonephritis acute
|
0.51%
1/198 • Number of events 1 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
0.00%
0/199 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
|
Injury, poisoning and procedural complications
Intentional overdose
|
0.51%
1/198 • Number of events 1 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
0.00%
0/199 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
|
Injury, poisoning and procedural complications
Wrong drug administered
|
0.00%
0/198 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
0.50%
1/199 • Number of events 1 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
1.0%
2/198 • Number of events 3 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
2.5%
5/199 • Number of events 6 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gallbladder cancer
|
0.51%
1/198 • Number of events 1 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
0.00%
0/199 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to liver
|
0.51%
1/198 • Number of events 1 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
0.00%
0/199 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic gastric cancer
|
0.51%
1/198 • Number of events 1 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
0.00%
0/199 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
|
Nervous system disorders
Cerebrovascular accident
|
0.51%
1/198 • Number of events 1 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
0.00%
0/199 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
|
Nervous system disorders
Hypoglycaemic seizure
|
0.00%
0/198 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
0.50%
1/199 • Number of events 1 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
|
Nervous system disorders
Hypoglycaemic unconsciousness
|
0.00%
0/198 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
1.5%
3/199 • Number of events 3 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
|
Psychiatric disorders
Acute stress disorder
|
0.51%
1/198 • Number of events 1 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
0.00%
0/199 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/198 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
0.50%
1/199 • Number of events 1 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
|
Respiratory, thoracic and mediastinal disorders
Lower respiratory tract inflammation
|
0.00%
0/198 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
0.50%
1/199 • Number of events 1 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
|
Vascular disorders
Orthostatic hypotension
|
0.51%
1/198 • Number of events 1 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
0.00%
0/199 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
|
Vascular disorders
Peripheral arterial occlusive disease
|
0.51%
1/198 • Number of events 1 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
0.00%
0/199 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
|
Vascular disorders
Peripheral vascular disorder
|
0.00%
0/198 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
0.50%
1/199 • Number of events 1 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
Other adverse events
| Measure |
Step-wise
n=198 participants at risk
In addition to insulin detemir once daily, insulin aspart was added step-wise starting at the randomisation visit (Week 0) with the first bolus before the largest meal, followed by a second bolus at the second largest meal at Week 11 in subjects with HbA1c ≥ 7.0% at Week 10, and a second or third bolus at Week 22 in subjects with HbA1c ≥ 7.0% at Week 21. Subjects on pre-trial metformin and pioglitazone continued their medication.
|
Basal-bolus
n=199 participants at risk
In addition to insulin detemir once daily, insulin aspart was added before each of the main meals (breakfast, lunch and dinner) starting at the randomisation visit. Subjects on pre-trial metformin and pioglitazone continued their medication.
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
4.0%
8/198 • Number of events 10 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
5.0%
10/199 • Number of events 10 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
|
General disorders
Oedema peripheral
|
2.0%
4/198 • Number of events 5 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
5.0%
10/199 • Number of events 10 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
|
Infections and infestations
Influenza
|
5.1%
10/198 • Number of events 11 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
6.5%
13/199 • Number of events 14 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
|
Infections and infestations
Nasopharyngitis
|
8.1%
16/198 • Number of events 19 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
6.5%
13/199 • Number of events 18 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
|
Nervous system disorders
Headache
|
5.1%
10/198 • Number of events 15 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
5.5%
11/199 • Number of events 13 • Adverse events were captured from the time of consent until 32 weeks of treatment and if needed were followed up after the final visit
Safety analysis set includes all subjects who received at least one dose of the investigational product or its comparator
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Novo Nordisk maintains the right to be informed of any Investigator plans for publication and to review any scientific paper, presentation, communication or other information concerning the investigation described in this protocol. Novo Nordisk reserves the right to prior review of such publications and to ask for delay of publication of individual site results until after the primary manuscript is accepted for publication.
- Publication restrictions are in place
Restriction type: OTHER