Trial Outcomes & Findings for The Efficacy of Insulin Degludec/Liraglutide in Controlling Glycaemia in Adults With Type 2 Diabetes Inadequately Controlled on GLP-1 Receptor Agonist and OAD Therapy (NCT NCT01676116)
NCT ID: NCT01676116
Last Updated: 2019-01-03
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
438 participants
Primary outcome timeframe
Week 0, week 26
Results posted on
2019-01-03
Participant Flow
The trial was conducted at 81 sites in 5 countries as follows: Australia: 5 sites; France: 7 sites; Hungary: 4 sites; Slovakia 6 sites; United States: 59 sites.
The duration of the screening period was 2 weeks. All subjects continued GLP-1 receptor agonist and metformin±pioglitazone±SU treatments in their pre-trial doses during the screening period.
Participant milestones
| Measure |
Insulin Degludec/Liraglutide + Oral Anti Diabetic Drugs (OADs)
Subjects were treated with subcutaneous (under the skin) once daily (OD) insulin degludec/liraglutide. Treatment with insulin degludec/liraglutide was initiated at 16 dose steps containing 16 units of insulin degludec and 0.6 mg liraglutide. Adjustment of the insulin degludec/liraglutide dose was performed twice weekly based on the mean of 3 preceding daily fasting self measured plasma glucose (SMPG) values on 3 consecutive days. The aim was to achieve a fasting plasma glucose (FPG) target of 4.0-5.0 mmol/L (72-90 mg/dL) and the maximum allowed dose was 50 dose steps (50 units insulin degludec/1.8 mg liraglutide). Subjects also continued their pre-trial OADs (metformin±pioglitazone±SU) treatment without changing the frequency or dose throughout the trial, unless there was a safety concern.
|
Liraglutide or Exenatide + OADs
Subjects continued on their pre-trial GLP-1 receptor agonist treatment with subcutaneous (under the skin) liraglutide (Victoza®) or exenatide (Byetta®) in stable pre-trial dose without changing the frequency or dose throughout the trial. Subjects also continued their pre-trial OADs (metformin±pioglitazone±SU) without changing the frequency or dose throughout the trial, unless there was a safety concern.
|
|---|---|---|
|
Overall Study
STARTED
|
292
|
146
|
|
Overall Study
COMPLETED
|
276
|
117
|
|
Overall Study
NOT COMPLETED
|
16
|
29
|
Reasons for withdrawal
| Measure |
Insulin Degludec/Liraglutide + Oral Anti Diabetic Drugs (OADs)
Subjects were treated with subcutaneous (under the skin) once daily (OD) insulin degludec/liraglutide. Treatment with insulin degludec/liraglutide was initiated at 16 dose steps containing 16 units of insulin degludec and 0.6 mg liraglutide. Adjustment of the insulin degludec/liraglutide dose was performed twice weekly based on the mean of 3 preceding daily fasting self measured plasma glucose (SMPG) values on 3 consecutive days. The aim was to achieve a fasting plasma glucose (FPG) target of 4.0-5.0 mmol/L (72-90 mg/dL) and the maximum allowed dose was 50 dose steps (50 units insulin degludec/1.8 mg liraglutide). Subjects also continued their pre-trial OADs (metformin±pioglitazone±SU) treatment without changing the frequency or dose throughout the trial, unless there was a safety concern.
|
Liraglutide or Exenatide + OADs
Subjects continued on their pre-trial GLP-1 receptor agonist treatment with subcutaneous (under the skin) liraglutide (Victoza®) or exenatide (Byetta®) in stable pre-trial dose without changing the frequency or dose throughout the trial. Subjects also continued their pre-trial OADs (metformin±pioglitazone±SU) without changing the frequency or dose throughout the trial, unless there was a safety concern.
|
|---|---|---|
|
Overall Study
Withdrawal criteria
|
2
|
14
|
|
Overall Study
Adverse Event
|
1
|
2
|
|
Overall Study
Unclassified
|
4
|
10
|
|
Overall Study
Protocol Violation
|
9
|
3
|
Baseline Characteristics
The Efficacy of Insulin Degludec/Liraglutide in Controlling Glycaemia in Adults With Type 2 Diabetes Inadequately Controlled on GLP-1 Receptor Agonist and OAD Therapy
Baseline characteristics by cohort
| Measure |
Insulin Degludec/Liraglutide + Oral Anti Diabetic Drugs (OADs)
n=292 Participants
Subjects were treated with subcutaneous (under the skin) once daily (OD) insulin degludec/liraglutide. Treatment with insulin degludec/liraglutide was initiated at 16 dose steps containing 16 units of insulin degludec and 0.6 mg liraglutide. Adjustment of the insulin degludec/liraglutide dose was performed twice weekly based on the mean of 3 preceding daily fasting self measured plasma glucose (SMPG) values on 3 consecutive days. The aim was to achieve a fasting plasma glucose (FPG) target of 4.0-5.0 mmol/L (72-90 mg/dL) and the maximum allowed dose was 50 dose steps (50 units insulin degludec/1.8 mg liraglutide). Subjects also continued their pre-trial OADs (metformin±pioglitazone±SU) treatment without changing the frequency or dose throughout the trial, unless there was a safety concern.
|
Liraglutide or Exenatide + OADs
n=146 Participants
Subjects continued on their pre-trial GLP-1 receptor agonist treatment with subcutaneous (under the skin) liraglutide (Victoza®) or exenatide (Byetta®) in stable pre-trial dose without changing the frequency or dose throughout the trial. Subjects also continued their pre-trial OADs (metformin±pioglitazone±SU) without changing the frequency or dose throughout the trial, unless there was a safety concern.
|
Total
n=438 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
58.3 years
STANDARD_DEVIATION 9.9 • n=99 Participants
|
58.4 years
STANDARD_DEVIATION 8.8 • n=107 Participants
|
58.3 years
STANDARD_DEVIATION 9.5 • n=206 Participants
|
|
Sex: Female, Male
Female
|
139 Participants
n=99 Participants
|
75 Participants
n=107 Participants
|
214 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
153 Participants
n=99 Participants
|
71 Participants
n=107 Participants
|
224 Participants
n=206 Participants
|
|
HbA1c
|
7.8 percentage of glycosylated haemoglobin
STANDARD_DEVIATION 0.6 • n=99 Participants
|
7.7 percentage of glycosylated haemoglobin
STANDARD_DEVIATION 0.6 • n=107 Participants
|
7.8 percentage of glycosylated haemoglobin
STANDARD_DEVIATION 0.6 • n=206 Participants
|
|
Body weight
|
95.6 kg
STANDARD_DEVIATION 16.6 • n=99 Participants
|
95.5 kg
STANDARD_DEVIATION 17.3 • n=107 Participants
|
95.5 kg
STANDARD_DEVIATION 16.8 • n=206 Participants
|
|
Fasting plasma glucose
|
9 mmol/L
STANDARD_DEVIATION 2.1 • n=99 Participants
|
9.4 mmol/L
STANDARD_DEVIATION 2.3 • n=107 Participants
|
9.1 mmol/L
STANDARD_DEVIATION 2.2 • n=206 Participants
|
PRIMARY outcome
Timeframe: Week 0, week 26Population: Full analysis set included all the randomised subjects. Missing values (including intermittent missing values) were imputed using the last observation carried forward (LOCF) method.
Outcome measures
| Measure |
Insulin Degludec/Liraglutide + Oral Anti Diabetic Drugs (OADs)
n=292 Participants
Subjects were treated with subcutaneous (under the skin) once daily (OD) insulin degludec/liraglutide. Treatment with insulin degludec/liraglutide was initiated at 16 dose steps containing 16 units of insulin degludec and 0.6 mg liraglutide. Adjustment of the insulin degludec/liraglutide dose was performed twice weekly based on the mean of 3 preceding daily fasting self measured plasma glucose (SMPG) values on 3 consecutive days. The aim was to achieve a fasting plasma glucose (FPG) target of 4.0-5.0 mmol/L (72-90 mg/dL) and the maximum allowed dose was 50 dose steps (50 units insulin degludec/1.8 mg liraglutide). Subjects also continued their pre-trial OADs (metformin±pioglitazone±SU) treatment without changing the frequency or dose throughout the trial, unless there was a safety concern.
|
Liraglutide or Exenatide + OADs
n=146 Participants
Subjects continued on their pre-trial GLP-1 receptor agonist treatment with subcutaneous (under the skin) liraglutide (Victoza®) or exenatide (Byetta®) in stable pre-trial dose without changing the frequency or dose throughout the trial. Subjects also continued their pre-trial OADs (metformin±pioglitazone±SU) without changing the frequency or dose throughout the trial, unless there was a safety concern.
|
|---|---|---|
|
Change in Glycosylated Haemoglobin (HbA1c) From Baseline (Randomisation, Visit 2)
|
-1.32 percentage of glycosylated haemoglobin
Standard Error 0.05
|
-0.37 percentage of glycosylated haemoglobin
Standard Error 0.07
|
SECONDARY outcome
Timeframe: Week 26Population: Full analysis set included all randomised subjects. Missing values (including intermittent missing values) were imputed using the last observation carried forward (LOCF) method.
Percentage of subjects achieving HbA1c below 7.0% after 26 weeks of treatment.
Outcome measures
| Measure |
Insulin Degludec/Liraglutide + Oral Anti Diabetic Drugs (OADs)
n=292 Participants
Subjects were treated with subcutaneous (under the skin) once daily (OD) insulin degludec/liraglutide. Treatment with insulin degludec/liraglutide was initiated at 16 dose steps containing 16 units of insulin degludec and 0.6 mg liraglutide. Adjustment of the insulin degludec/liraglutide dose was performed twice weekly based on the mean of 3 preceding daily fasting self measured plasma glucose (SMPG) values on 3 consecutive days. The aim was to achieve a fasting plasma glucose (FPG) target of 4.0-5.0 mmol/L (72-90 mg/dL) and the maximum allowed dose was 50 dose steps (50 units insulin degludec/1.8 mg liraglutide). Subjects also continued their pre-trial OADs (metformin±pioglitazone±SU) treatment without changing the frequency or dose throughout the trial, unless there was a safety concern.
|
Liraglutide or Exenatide + OADs
n=146 Participants
Subjects continued on their pre-trial GLP-1 receptor agonist treatment with subcutaneous (under the skin) liraglutide (Victoza®) or exenatide (Byetta®) in stable pre-trial dose without changing the frequency or dose throughout the trial. Subjects also continued their pre-trial OADs (metformin±pioglitazone±SU) without changing the frequency or dose throughout the trial, unless there was a safety concern.
|
|---|---|---|
|
Responders Achieving Pre-defined Target: HbA1c Below 7.0% (53 mmol/Mol)
|
75.3 Percentage
|
35.6 Percentage
|
SECONDARY outcome
Timeframe: Week 26Population: Full analysis set included all randomised subjects. Missing values (including intermittent missing values) were imputed using the last observation carried forward (LOCF) method.
Percentage of responders achieving pre-defined target for HbA1c - HbA1c ≤ 6.5% (48 mmol/mol).
Outcome measures
| Measure |
Insulin Degludec/Liraglutide + Oral Anti Diabetic Drugs (OADs)
n=292 Participants
Subjects were treated with subcutaneous (under the skin) once daily (OD) insulin degludec/liraglutide. Treatment with insulin degludec/liraglutide was initiated at 16 dose steps containing 16 units of insulin degludec and 0.6 mg liraglutide. Adjustment of the insulin degludec/liraglutide dose was performed twice weekly based on the mean of 3 preceding daily fasting self measured plasma glucose (SMPG) values on 3 consecutive days. The aim was to achieve a fasting plasma glucose (FPG) target of 4.0-5.0 mmol/L (72-90 mg/dL) and the maximum allowed dose was 50 dose steps (50 units insulin degludec/1.8 mg liraglutide). Subjects also continued their pre-trial OADs (metformin±pioglitazone±SU) treatment without changing the frequency or dose throughout the trial, unless there was a safety concern.
|
Liraglutide or Exenatide + OADs
n=146 Participants
Subjects continued on their pre-trial GLP-1 receptor agonist treatment with subcutaneous (under the skin) liraglutide (Victoza®) or exenatide (Byetta®) in stable pre-trial dose without changing the frequency or dose throughout the trial. Subjects also continued their pre-trial OADs (metformin±pioglitazone±SU) without changing the frequency or dose throughout the trial, unless there was a safety concern.
|
|---|---|---|
|
Responders Achieving Pre-defined Target: HbA1c Below or Equal to 6.5% (48 mmol/Mol)
|
63 Percentage
|
22.6 Percentage
|
SECONDARY outcome
Timeframe: Week 0, week 26Population: Full analysis set included all randomised subjects. Missing values (including intermittent missing values) were imputed using the last observation carried forward (LOCF) method.
Mean change in body weight after 26 weeks of treatment.
Outcome measures
| Measure |
Insulin Degludec/Liraglutide + Oral Anti Diabetic Drugs (OADs)
n=292 Participants
Subjects were treated with subcutaneous (under the skin) once daily (OD) insulin degludec/liraglutide. Treatment with insulin degludec/liraglutide was initiated at 16 dose steps containing 16 units of insulin degludec and 0.6 mg liraglutide. Adjustment of the insulin degludec/liraglutide dose was performed twice weekly based on the mean of 3 preceding daily fasting self measured plasma glucose (SMPG) values on 3 consecutive days. The aim was to achieve a fasting plasma glucose (FPG) target of 4.0-5.0 mmol/L (72-90 mg/dL) and the maximum allowed dose was 50 dose steps (50 units insulin degludec/1.8 mg liraglutide). Subjects also continued their pre-trial OADs (metformin±pioglitazone±SU) treatment without changing the frequency or dose throughout the trial, unless there was a safety concern.
|
Liraglutide or Exenatide + OADs
n=146 Participants
Subjects continued on their pre-trial GLP-1 receptor agonist treatment with subcutaneous (under the skin) liraglutide (Victoza®) or exenatide (Byetta®) in stable pre-trial dose without changing the frequency or dose throughout the trial. Subjects also continued their pre-trial OADs (metformin±pioglitazone±SU) without changing the frequency or dose throughout the trial, unless there was a safety concern.
|
|---|---|---|
|
Change From Baseline in Body Weight
|
2 kg
Standard Deviation 3.9
|
-0.8 kg
Standard Deviation 3.0
|
SECONDARY outcome
Timeframe: Week 0, week 26Population: Full analysis set included all randomised subjects. A total of 430 subjects contributed to the analysis. Missing values (including intermittent missing values) were imputed using the last observation carried forward (LOCF) method.
Mean change in fasting plasma glucose from baseline, after 26 weeks of treatment.
Outcome measures
| Measure |
Insulin Degludec/Liraglutide + Oral Anti Diabetic Drugs (OADs)
n=285 Participants
Subjects were treated with subcutaneous (under the skin) once daily (OD) insulin degludec/liraglutide. Treatment with insulin degludec/liraglutide was initiated at 16 dose steps containing 16 units of insulin degludec and 0.6 mg liraglutide. Adjustment of the insulin degludec/liraglutide dose was performed twice weekly based on the mean of 3 preceding daily fasting self measured plasma glucose (SMPG) values on 3 consecutive days. The aim was to achieve a fasting plasma glucose (FPG) target of 4.0-5.0 mmol/L (72-90 mg/dL) and the maximum allowed dose was 50 dose steps (50 units insulin degludec/1.8 mg liraglutide). Subjects also continued their pre-trial OADs (metformin±pioglitazone±SU) treatment without changing the frequency or dose throughout the trial, unless there was a safety concern.
|
Liraglutide or Exenatide + OADs
n=145 Participants
Subjects continued on their pre-trial GLP-1 receptor agonist treatment with subcutaneous (under the skin) liraglutide (Victoza®) or exenatide (Byetta®) in stable pre-trial dose without changing the frequency or dose throughout the trial. Subjects also continued their pre-trial OADs (metformin±pioglitazone±SU) without changing the frequency or dose throughout the trial, unless there was a safety concern.
|
|---|---|---|
|
Change From Baseline in Fasting Plasma Glucose (FPG)
|
-2.98 mmol/L
Standard Deviation 2.28
|
-0.6 mmol/L
Standard Deviation 2.74
|
SECONDARY outcome
Timeframe: After 26 weeks of treatmentPopulation: Full analysis set included all randomised subjects. A total of 436 subjects contributed to the analysis.
Rate (events per 100 patient years of exposure) of treatment-emergent confirmed hypoglycaemic episodes. The pool of severe and minor hypoglycaemic episodes was referred to as confirmed hypoglycaemic episodes. Severe hypoglycaemia was categorised as an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as an episode with symptoms consistent with hypoglycaemia with confirmation by blood glucose \<2.8 mmol/L (50 mg/dL) or PG \<3.1 mmol/L (56 mg/dL), and which was handled by the subject himself/herself, or any asymptomatic blood glucose value \<2.8 mmol/L (50 mg/dL) or PG value \<3.1 mmol/L (56 mg/dL).
Outcome measures
| Measure |
Insulin Degludec/Liraglutide + Oral Anti Diabetic Drugs (OADs)
n=291 Participants
Subjects were treated with subcutaneous (under the skin) once daily (OD) insulin degludec/liraglutide. Treatment with insulin degludec/liraglutide was initiated at 16 dose steps containing 16 units of insulin degludec and 0.6 mg liraglutide. Adjustment of the insulin degludec/liraglutide dose was performed twice weekly based on the mean of 3 preceding daily fasting self measured plasma glucose (SMPG) values on 3 consecutive days. The aim was to achieve a fasting plasma glucose (FPG) target of 4.0-5.0 mmol/L (72-90 mg/dL) and the maximum allowed dose was 50 dose steps (50 units insulin degludec/1.8 mg liraglutide). Subjects also continued their pre-trial OADs (metformin±pioglitazone±SU) treatment without changing the frequency or dose throughout the trial, unless there was a safety concern.
|
Liraglutide or Exenatide + OADs
n=145 Participants
Subjects continued on their pre-trial GLP-1 receptor agonist treatment with subcutaneous (under the skin) liraglutide (Victoza®) or exenatide (Byetta®) in stable pre-trial dose without changing the frequency or dose throughout the trial. Subjects also continued their pre-trial OADs (metformin±pioglitazone±SU) without changing the frequency or dose throughout the trial, unless there was a safety concern.
|
|---|---|---|
|
Number of Severe or Minor Hypoglycaemic Episodes
|
281.7 events per 100 patient years of exposure
|
12.1 events per 100 patient years of exposure
|
SECONDARY outcome
Timeframe: After 26 weeks of treatmentPopulation: Full analysis set included all randomised subjects. A total of 436 subjects contributed to the analysis.
Rate (events per 100 exposure years) of treatment-emergent adverse events (an event that had onset date (or an increase in severity) on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment) which occurred during the 26 weeks of treatment.
Outcome measures
| Measure |
Insulin Degludec/Liraglutide + Oral Anti Diabetic Drugs (OADs)
n=291 Participants
Subjects were treated with subcutaneous (under the skin) once daily (OD) insulin degludec/liraglutide. Treatment with insulin degludec/liraglutide was initiated at 16 dose steps containing 16 units of insulin degludec and 0.6 mg liraglutide. Adjustment of the insulin degludec/liraglutide dose was performed twice weekly based on the mean of 3 preceding daily fasting self measured plasma glucose (SMPG) values on 3 consecutive days. The aim was to achieve a fasting plasma glucose (FPG) target of 4.0-5.0 mmol/L (72-90 mg/dL) and the maximum allowed dose was 50 dose steps (50 units insulin degludec/1.8 mg liraglutide). Subjects also continued their pre-trial OADs (metformin±pioglitazone±SU) treatment without changing the frequency or dose throughout the trial, unless there was a safety concern.
|
Liraglutide or Exenatide + OADs
n=145 Participants
Subjects continued on their pre-trial GLP-1 receptor agonist treatment with subcutaneous (under the skin) liraglutide (Victoza®) or exenatide (Byetta®) in stable pre-trial dose without changing the frequency or dose throughout the trial. Subjects also continued their pre-trial OADs (metformin±pioglitazone±SU) without changing the frequency or dose throughout the trial, unless there was a safety concern.
|
|---|---|---|
|
Number of Adverse Events (AEs)
|
410.1 events per 100 exposure years
|
364.3 events per 100 exposure years
|
SECONDARY outcome
Timeframe: Week 0, week 26Population: Full analysis set included all randomised subjects. A total of 436 subjects contributed to the analysis. Missing values (including intermittent missing values) were imputed using the last observation carried forward (LOCF) method.
The patient related outcome is calculated based on TRIM-D questionnaire. The TRIM-D questionnaire consists of 5 sub-domains (treatment burden, daily life, diabetes management, compliance and psychological health), where each question is scored to a 1-5-point scale with a higher score indicating a better health state (less negative impact). Mean TRIM-D individual sub-domain scores and total score are later transformed to a 0-100 scale for analysis. The mean change in scores from baseline to 26 weeks for all the individual sub domains and total scores are presented here.
Outcome measures
| Measure |
Insulin Degludec/Liraglutide + Oral Anti Diabetic Drugs (OADs)
n=290 Participants
Subjects were treated with subcutaneous (under the skin) once daily (OD) insulin degludec/liraglutide. Treatment with insulin degludec/liraglutide was initiated at 16 dose steps containing 16 units of insulin degludec and 0.6 mg liraglutide. Adjustment of the insulin degludec/liraglutide dose was performed twice weekly based on the mean of 3 preceding daily fasting self measured plasma glucose (SMPG) values on 3 consecutive days. The aim was to achieve a fasting plasma glucose (FPG) target of 4.0-5.0 mmol/L (72-90 mg/dL) and the maximum allowed dose was 50 dose steps (50 units insulin degludec/1.8 mg liraglutide). Subjects also continued their pre-trial OADs (metformin±pioglitazone±SU) treatment without changing the frequency or dose throughout the trial, unless there was a safety concern.
|
Liraglutide or Exenatide + OADs
n=146 Participants
Subjects continued on their pre-trial GLP-1 receptor agonist treatment with subcutaneous (under the skin) liraglutide (Victoza®) or exenatide (Byetta®) in stable pre-trial dose without changing the frequency or dose throughout the trial. Subjects also continued their pre-trial OADs (metformin±pioglitazone±SU) without changing the frequency or dose throughout the trial, unless there was a safety concern.
|
|---|---|---|
|
Change From Baseline in Patient Reported Outcomes (PROs) Based on the Treatment Related Impact Measure - Diabetes (TRIM-D)
TRIM-D Treatment Burden Score
|
10.8 Scores on a scale
Standard Deviation 18.8
|
5.7 Scores on a scale
Standard Deviation 19.3
|
|
Change From Baseline in Patient Reported Outcomes (PROs) Based on the Treatment Related Impact Measure - Diabetes (TRIM-D)
TRIM-D Daily Life Score
|
6.3 Scores on a scale
Standard Deviation 18.4
|
0.8 Scores on a scale
Standard Deviation 18.2
|
|
Change From Baseline in Patient Reported Outcomes (PROs) Based on the Treatment Related Impact Measure - Diabetes (TRIM-D)
TRIM-D Diabetes Management Score
|
10.9 Scores on a scale
Standard Deviation 21.3
|
4.1 Scores on a scale
Standard Deviation 19.8
|
|
Change From Baseline in Patient Reported Outcomes (PROs) Based on the Treatment Related Impact Measure - Diabetes (TRIM-D)
TRIM-D Compliance Score
|
8.9 Scores on a scale
Standard Deviation 17.3
|
4.3 Scores on a scale
Standard Deviation 15.9
|
|
Change From Baseline in Patient Reported Outcomes (PROs) Based on the Treatment Related Impact Measure - Diabetes (TRIM-D)
TRIM-D Psychological Health Score
|
7.3 Scores on a scale
Standard Deviation 14.7
|
1.4 Scores on a scale
Standard Deviation 16.5
|
|
Change From Baseline in Patient Reported Outcomes (PROs) Based on the Treatment Related Impact Measure - Diabetes (TRIM-D)
TRIM-D Total Score
|
8.7 Scores on a scale
Standard Deviation 12
|
3.1 Scores on a scale
Standard Deviation 12.2
|
SECONDARY outcome
Timeframe: Week 0, week 26Population: Full analysis set included all randomised subjects. A total of 436 subjects contributed to the analysis. Missing values (including intermittent missing values) were imputed using the last observation carried forward (LOCF) method.
Mean change in diabetes treatment satisfaction questionnaire (DTSQs) scores from baseline. The scores ranged from 0 to 6. Higher total score on a 0-6 point scale indicates a general higher treatment satisfaction, whereas higher score on perceived frequency of hyperglycaemia and perceived frequency of hypoglycaemia indicate that blood glucose levels are out of the target range.
Outcome measures
| Measure |
Insulin Degludec/Liraglutide + Oral Anti Diabetic Drugs (OADs)
n=290 Participants
Subjects were treated with subcutaneous (under the skin) once daily (OD) insulin degludec/liraglutide. Treatment with insulin degludec/liraglutide was initiated at 16 dose steps containing 16 units of insulin degludec and 0.6 mg liraglutide. Adjustment of the insulin degludec/liraglutide dose was performed twice weekly based on the mean of 3 preceding daily fasting self measured plasma glucose (SMPG) values on 3 consecutive days. The aim was to achieve a fasting plasma glucose (FPG) target of 4.0-5.0 mmol/L (72-90 mg/dL) and the maximum allowed dose was 50 dose steps (50 units insulin degludec/1.8 mg liraglutide). Subjects also continued their pre-trial OADs (metformin±pioglitazone±SU) treatment without changing the frequency or dose throughout the trial, unless there was a safety concern.
|
Liraglutide or Exenatide + OADs
n=146 Participants
Subjects continued on their pre-trial GLP-1 receptor agonist treatment with subcutaneous (under the skin) liraglutide (Victoza®) or exenatide (Byetta®) in stable pre-trial dose without changing the frequency or dose throughout the trial. Subjects also continued their pre-trial OADs (metformin±pioglitazone±SU) without changing the frequency or dose throughout the trial, unless there was a safety concern.
|
|---|---|---|
|
Change From Baseline in Patient Reported Outcomes (PROs) Based on Diabetes Treatment Satisfaction Questionnaire (DTSQ).
Treatment satisfaction scale total
|
3.1 Scores on a scale
Standard Deviation 5.6
|
1.1 Scores on a scale
Standard Deviation 5.0
|
|
Change From Baseline in Patient Reported Outcomes (PROs) Based on Diabetes Treatment Satisfaction Questionnaire (DTSQ).
Hyperglycaemia
|
-1.8 Scores on a scale
Standard Deviation 2.1
|
-0.6 Scores on a scale
Standard Deviation 1.9
|
|
Change From Baseline in Patient Reported Outcomes (PROs) Based on Diabetes Treatment Satisfaction Questionnaire (DTSQ).
Hypoglycaemia
|
0.2 Scores on a scale
Standard Deviation 1.7
|
-0.1 Scores on a scale
Standard Deviation 1.5
|
Adverse Events
Insulin Degludec/Liraglutide +OADs
Serious events: 9 serious events
Other events: 88 other events
Deaths: 0 deaths
Liraglutide or Exenatide + OADs
Serious events: 3 serious events
Other events: 39 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Insulin Degludec/Liraglutide +OADs
n=291 participants at risk
Subjects were treated with subcutaneous (under the skin) once daily (OD) insulin degludec/liraglutide. Insulin degludec/liraglutide was dosed on an individual basis. Subjects also continued their pre-trial OADs (metformin±pioglitazone±SU) treatment without changing the frequency or dose throughout the trial, unless there was a safety concern.
|
Liraglutide or Exenatide + OADs
n=145 participants at risk
Subjects continued on their pre-trial GLP-1 receptor agonist treatment with subcutaneous (under the skin) liraglutide (Victoza®) or exenatide (Byetta®) in stable pre-trial dose without changing the frequency or dose throughout the trial. Subjects also continued their pre-trial OADs (metformin±pioglitazone±SU) without changing the frequency or dose throughout the trial, unless there was a safety concern.
|
|---|---|---|
|
Endocrine disorders
Adrenal insufficiency
|
0.34%
1/291 • Number of events 1 • Adverse events from the first trial-related activity after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27) are reported.
Safety analysis set included a total of 436 subjects; (291 in the Insulin degludec/liraglutide+OADs arm and 145 in the Liraglutide or exenatide+OADs arm).
|
0.00%
0/145 • Adverse events from the first trial-related activity after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27) are reported.
Safety analysis set included a total of 436 subjects; (291 in the Insulin degludec/liraglutide+OADs arm and 145 in the Liraglutide or exenatide+OADs arm).
|
|
Cardiac disorders
Atrial fibrillation
|
0.34%
1/291 • Number of events 1 • Adverse events from the first trial-related activity after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27) are reported.
Safety analysis set included a total of 436 subjects; (291 in the Insulin degludec/liraglutide+OADs arm and 145 in the Liraglutide or exenatide+OADs arm).
|
0.00%
0/145 • Adverse events from the first trial-related activity after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27) are reported.
Safety analysis set included a total of 436 subjects; (291 in the Insulin degludec/liraglutide+OADs arm and 145 in the Liraglutide or exenatide+OADs arm).
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.34%
1/291 • Number of events 1 • Adverse events from the first trial-related activity after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27) are reported.
Safety analysis set included a total of 436 subjects; (291 in the Insulin degludec/liraglutide+OADs arm and 145 in the Liraglutide or exenatide+OADs arm).
|
0.00%
0/145 • Adverse events from the first trial-related activity after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27) are reported.
Safety analysis set included a total of 436 subjects; (291 in the Insulin degludec/liraglutide+OADs arm and 145 in the Liraglutide or exenatide+OADs arm).
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/291 • Adverse events from the first trial-related activity after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27) are reported.
Safety analysis set included a total of 436 subjects; (291 in the Insulin degludec/liraglutide+OADs arm and 145 in the Liraglutide or exenatide+OADs arm).
|
0.69%
1/145 • Number of events 1 • Adverse events from the first trial-related activity after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27) are reported.
Safety analysis set included a total of 436 subjects; (291 in the Insulin degludec/liraglutide+OADs arm and 145 in the Liraglutide or exenatide+OADs arm).
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.34%
1/291 • Number of events 1 • Adverse events from the first trial-related activity after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27) are reported.
Safety analysis set included a total of 436 subjects; (291 in the Insulin degludec/liraglutide+OADs arm and 145 in the Liraglutide or exenatide+OADs arm).
|
0.00%
0/145 • Adverse events from the first trial-related activity after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27) are reported.
Safety analysis set included a total of 436 subjects; (291 in the Insulin degludec/liraglutide+OADs arm and 145 in the Liraglutide or exenatide+OADs arm).
|
|
Injury, poisoning and procedural complications
Foot fracture
|
0.00%
0/291 • Adverse events from the first trial-related activity after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27) are reported.
Safety analysis set included a total of 436 subjects; (291 in the Insulin degludec/liraglutide+OADs arm and 145 in the Liraglutide or exenatide+OADs arm).
|
0.69%
1/145 • Number of events 1 • Adverse events from the first trial-related activity after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27) are reported.
Safety analysis set included a total of 436 subjects; (291 in the Insulin degludec/liraglutide+OADs arm and 145 in the Liraglutide or exenatide+OADs arm).
|
|
Nervous system disorders
Lacunar infarction
|
0.34%
1/291 • Number of events 1 • Adverse events from the first trial-related activity after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27) are reported.
Safety analysis set included a total of 436 subjects; (291 in the Insulin degludec/liraglutide+OADs arm and 145 in the Liraglutide or exenatide+OADs arm).
|
0.00%
0/145 • Adverse events from the first trial-related activity after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27) are reported.
Safety analysis set included a total of 436 subjects; (291 in the Insulin degludec/liraglutide+OADs arm and 145 in the Liraglutide or exenatide+OADs arm).
|
|
General disorders
Non-cardiac chest pain
|
0.34%
1/291 • Number of events 1 • Adverse events from the first trial-related activity after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27) are reported.
Safety analysis set included a total of 436 subjects; (291 in the Insulin degludec/liraglutide+OADs arm and 145 in the Liraglutide or exenatide+OADs arm).
|
0.00%
0/145 • Adverse events from the first trial-related activity after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27) are reported.
Safety analysis set included a total of 436 subjects; (291 in the Insulin degludec/liraglutide+OADs arm and 145 in the Liraglutide or exenatide+OADs arm).
|
|
Vascular disorders
Peripheral artery thrombosis
|
0.34%
1/291 • Number of events 1 • Adverse events from the first trial-related activity after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27) are reported.
Safety analysis set included a total of 436 subjects; (291 in the Insulin degludec/liraglutide+OADs arm and 145 in the Liraglutide or exenatide+OADs arm).
|
0.00%
0/145 • Adverse events from the first trial-related activity after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27) are reported.
Safety analysis set included a total of 436 subjects; (291 in the Insulin degludec/liraglutide+OADs arm and 145 in the Liraglutide or exenatide+OADs arm).
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pituitary tumour
|
0.34%
1/291 • Number of events 1 • Adverse events from the first trial-related activity after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27) are reported.
Safety analysis set included a total of 436 subjects; (291 in the Insulin degludec/liraglutide+OADs arm and 145 in the Liraglutide or exenatide+OADs arm).
|
0.00%
0/145 • Adverse events from the first trial-related activity after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27) are reported.
Safety analysis set included a total of 436 subjects; (291 in the Insulin degludec/liraglutide+OADs arm and 145 in the Liraglutide or exenatide+OADs arm).
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.34%
1/291 • Number of events 1 • Adverse events from the first trial-related activity after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27) are reported.
Safety analysis set included a total of 436 subjects; (291 in the Insulin degludec/liraglutide+OADs arm and 145 in the Liraglutide or exenatide+OADs arm).
|
0.00%
0/145 • Adverse events from the first trial-related activity after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27) are reported.
Safety analysis set included a total of 436 subjects; (291 in the Insulin degludec/liraglutide+OADs arm and 145 in the Liraglutide or exenatide+OADs arm).
|
|
Nervous system disorders
Sciatica
|
0.00%
0/291 • Adverse events from the first trial-related activity after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27) are reported.
Safety analysis set included a total of 436 subjects; (291 in the Insulin degludec/liraglutide+OADs arm and 145 in the Liraglutide or exenatide+OADs arm).
|
0.69%
1/145 • Number of events 1 • Adverse events from the first trial-related activity after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27) are reported.
Safety analysis set included a total of 436 subjects; (291 in the Insulin degludec/liraglutide+OADs arm and 145 in the Liraglutide or exenatide+OADs arm).
|
|
Musculoskeletal and connective tissue disorders
Spinal pain
|
0.34%
1/291 • Number of events 1 • Adverse events from the first trial-related activity after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27) are reported.
Safety analysis set included a total of 436 subjects; (291 in the Insulin degludec/liraglutide+OADs arm and 145 in the Liraglutide or exenatide+OADs arm).
|
0.00%
0/145 • Adverse events from the first trial-related activity after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27) are reported.
Safety analysis set included a total of 436 subjects; (291 in the Insulin degludec/liraglutide+OADs arm and 145 in the Liraglutide or exenatide+OADs arm).
|
|
Surgical and medical procedures
Thrombectomy
|
0.34%
1/291 • Number of events 1 • Adverse events from the first trial-related activity after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27) are reported.
Safety analysis set included a total of 436 subjects; (291 in the Insulin degludec/liraglutide+OADs arm and 145 in the Liraglutide or exenatide+OADs arm).
|
0.00%
0/145 • Adverse events from the first trial-related activity after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27) are reported.
Safety analysis set included a total of 436 subjects; (291 in the Insulin degludec/liraglutide+OADs arm and 145 in the Liraglutide or exenatide+OADs arm).
|
|
Nervous system disorders
Transient ischaemic attack
|
0.34%
1/291 • Number of events 1 • Adverse events from the first trial-related activity after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27) are reported.
Safety analysis set included a total of 436 subjects; (291 in the Insulin degludec/liraglutide+OADs arm and 145 in the Liraglutide or exenatide+OADs arm).
|
0.00%
0/145 • Adverse events from the first trial-related activity after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27) are reported.
Safety analysis set included a total of 436 subjects; (291 in the Insulin degludec/liraglutide+OADs arm and 145 in the Liraglutide or exenatide+OADs arm).
|
Other adverse events
| Measure |
Insulin Degludec/Liraglutide +OADs
n=291 participants at risk
Subjects were treated with subcutaneous (under the skin) once daily (OD) insulin degludec/liraglutide. Insulin degludec/liraglutide was dosed on an individual basis. Subjects also continued their pre-trial OADs (metformin±pioglitazone±SU) treatment without changing the frequency or dose throughout the trial, unless there was a safety concern.
|
Liraglutide or Exenatide + OADs
n=145 participants at risk
Subjects continued on their pre-trial GLP-1 receptor agonist treatment with subcutaneous (under the skin) liraglutide (Victoza®) or exenatide (Byetta®) in stable pre-trial dose without changing the frequency or dose throughout the trial. Subjects also continued their pre-trial OADs (metformin±pioglitazone±SU) without changing the frequency or dose throughout the trial, unless there was a safety concern.
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
4.5%
13/291 • Number of events 18 • Adverse events from the first trial-related activity after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27) are reported.
Safety analysis set included a total of 436 subjects; (291 in the Insulin degludec/liraglutide+OADs arm and 145 in the Liraglutide or exenatide+OADs arm).
|
5.5%
8/145 • Number of events 9 • Adverse events from the first trial-related activity after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27) are reported.
Safety analysis set included a total of 436 subjects; (291 in the Insulin degludec/liraglutide+OADs arm and 145 in the Liraglutide or exenatide+OADs arm).
|
|
Nervous system disorders
Headache
|
9.3%
27/291 • Number of events 31 • Adverse events from the first trial-related activity after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27) are reported.
Safety analysis set included a total of 436 subjects; (291 in the Insulin degludec/liraglutide+OADs arm and 145 in the Liraglutide or exenatide+OADs arm).
|
6.2%
9/145 • Number of events 14 • Adverse events from the first trial-related activity after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27) are reported.
Safety analysis set included a total of 436 subjects; (291 in the Insulin degludec/liraglutide+OADs arm and 145 in the Liraglutide or exenatide+OADs arm).
|
|
Investigations
Lipase increased
|
10.0%
29/291 • Number of events 31 • Adverse events from the first trial-related activity after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27) are reported.
Safety analysis set included a total of 436 subjects; (291 in the Insulin degludec/liraglutide+OADs arm and 145 in the Liraglutide or exenatide+OADs arm).
|
4.8%
7/145 • Number of events 8 • Adverse events from the first trial-related activity after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27) are reported.
Safety analysis set included a total of 436 subjects; (291 in the Insulin degludec/liraglutide+OADs arm and 145 in the Liraglutide or exenatide+OADs arm).
|
|
Infections and infestations
Nasopharyngitis
|
8.9%
26/291 • Number of events 31 • Adverse events from the first trial-related activity after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27) are reported.
Safety analysis set included a total of 436 subjects; (291 in the Insulin degludec/liraglutide+OADs arm and 145 in the Liraglutide or exenatide+OADs arm).
|
13.1%
19/145 • Number of events 20 • Adverse events from the first trial-related activity after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27) are reported.
Safety analysis set included a total of 436 subjects; (291 in the Insulin degludec/liraglutide+OADs arm and 145 in the Liraglutide or exenatide+OADs arm).
|
|
Infections and infestations
Upper respiratory tract infection
|
6.2%
18/291 • Number of events 18 • Adverse events from the first trial-related activity after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27) are reported.
Safety analysis set included a total of 436 subjects; (291 in the Insulin degludec/liraglutide+OADs arm and 145 in the Liraglutide or exenatide+OADs arm).
|
5.5%
8/145 • Number of events 9 • Adverse events from the first trial-related activity after the subject had signed the informed consent until the end of the post-treatment follow-up period (week 27) are reported.
Safety analysis set included a total of 436 subjects; (291 in the Insulin degludec/liraglutide+OADs arm and 145 in the Liraglutide or exenatide+OADs arm).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee At the end of the trial, one or more public disclosures may be prepared collaboratively by the Investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for up to 60 days to protect intellectual property.
- Publication restrictions are in place
Restriction type: OTHER