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The Effect of Insulin Degludec in Combination With Liraglutide and Metformin in Subjects With Type 2 Diabetes Qualifying for Treatment Intensification

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ClinicalTrials.gov Identifier: NCT01664247
Recruitment Status : Completed
First Posted : August 14, 2012
Results First Posted : April 20, 2016
Last Update Posted : September 25, 2017
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Diabetes
Diabetes Mellitus, Type 2
Interventions Drug: insulin degludec
Drug: placebo
Drug: liraglutide
Enrollment 346

Recruitment Details The trial was conducted at 129 sites in 11 countries randomised subjects: Canada (7), France (10), Germany (8), Israel (6), Italy (7), Serbia (7), South Africa (6), Ukraine (4), United Arab Emirates (3), United Kingdom (6), and United States (65).
Pre-assignment Details  
Arm/Group Title IDeg Placebo
Hide Arm/Group Description Liraglutide treatment was initiated on 0.6 mg daily for one week and increased further after the second week in the run-in period. In the randomized period, Insulin degludec (IDeg, 100 U/mL, in a 3 mL prefilled pen PDS290) treatment was recommended to be initiated and administered subcutaneously (under the skin) once daily (OD) with 10 units. After that it was titrated once weekly. If one or more of the pre-breakfast plasma glucose values were below a certain range, the subjects were to reduce the insulin dose. Subjects continued on metformin (1500/day) treatment at the stable, pre-trial dose and maintained dosing frequency levels throughout the trial period. Placebo treatment (3 mL prefilled pen) in combination with Liraglutide (Lira,1.8 mg/daily, 3 mL prefilled pen) once daily was given subcutaneously (under the skin) in the thigh, abdomen or upper arm (deltoid) at any time of the day according to the subject’s choice for 26 weeks of treatment period. Subjects continued on metformin (1500/day) treatment at the stable, pre-trial dose and maintained dosing frequency levels throughout the trial period.
Period Title: Overall Study
Started 174 172
Exposed 173 [1] 170 [2]
Completed 160 131
Not Completed 14 41
Reason Not Completed
Adverse Event             5             3
Protocol Violation             3             5
Withdrawal Criteria             1             4
Unclassified             5             29
[1]
1 subject was randomised in error and withdrew before exposure to the drug
[2]
Two subjects were randomised in error and withdrew prior to exposure to drug
Arm/Group Title IDeg Placebo Total
Hide Arm/Group Description Liraglutide treatment was initiated on 0.6 mg daily for one week and increased further after the second week in the run-in period. In the randomized period, Insulin degludec (IDeg, 100 U/mL, in a 3 mL prefilled pen PDS290) treatment was recommended to be initiated and administered subcutaneously (under the skin) once daily (OD) with 10 units. After that it was titrated once weekly. If one or more of the pre-breakfast plasma glucose values were below a certain range, the subjects were to reduce the insulin dose. Subjects continued on metformin (1500/day) treatment at the stable, pre-trial dose and maintained dosing frequency levels throughout the trial period. Placebo treatment (3 mL prefilled pen) in combination with Liraglutide (Lira,1.8 mg/daily, 3 mL prefilled pen) once daily was given subcutaneously (under the skin) in the thigh, abdomen or upper arm (deltoid) at any time of the day according to the subject’s choice for 26 weeks of treatment period. Subjects continued on metformin (1500/day) treatment at the stable, pre-trial dose and maintained dosing frequency levels throughout the trial period. Total of all reporting groups
Overall Number of Baseline Participants 174 172 346
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 174 participants 172 participants 346 participants
57.0  (10.0) 57.3  (9.4) 57.2  (9.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 174 participants 172 participants 346 participants
Female
76
  43.7%
68
  39.5%
144
  41.6%
Male
98
  56.3%
104
  60.5%
202
  58.4%
Glycosylated haemoglobin (HbA1c)  
Mean (Standard Deviation)
Unit of measure:  Percentage of glycosylated haemoglobin
Number Analyzed 174 participants 172 participants 346 participants
7.5  (0.6) 7.6  (0.6) 7.6  (0.6)
Fasting plasma glucose (FPG)  
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 174 participants 172 participants 346 participants
8.7  (2.1) 9.1  (2.2) 8.9  (2.2)
1.Primary Outcome
Title Change From Baseline in Glycosylated Haemoglobin (HbA1c) (%)
Hide Description Change from baseline in HbA1c after 26 weeks of treatment
Time Frame Week 0, week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised subjects and missing data was imputed using last observation carried forward (LOCF).
Arm/Group Title IDeg Placebo
Hide Arm/Group Description:
Liraglutide treatment was initiated on 0.6 mg daily for one week and increased further after the second week in the run-in period. In the randomized period, Insulin degludec (IDeg, 100 U/mL, in a 3 mL prefilled pen PDS290) treatment was recommended to be initiated and administered subcutaneously (under the skin) once daily (OD) with 10 units. After that it was titrated once weekly. If one or more of the pre-breakfast plasma glucose values were below a certain range, the subjects were to reduce the insulin dose. Subjects continued on metformin (1500/day) treatment at the stable, pre-trial dose and maintained dosing frequency levels throughout the trial period.
Placebo treatment (3 mL prefilled pen) in combination with Liraglutide (Lira,1.8 mg/daily, 3 mL prefilled pen) once daily was given subcutaneously (under the skin) in the thigh, abdomen or upper arm (deltoid) at any time of the day according to the subject’s choice for 26 weeks of treatment period. Subjects continued on metformin (1500/day) treatment at the stable, pre-trial dose and maintained dosing frequency levels throughout the trial period.
Overall Number of Participants Analyzed 174 172
Least Squares Mean (Standard Error)
Unit of Measure: percentage of glycosylated haemoglobin
-0.99  (0.08) -0.07  (0.08)
2.Secondary Outcome
Title Change From Baseline in Fasting Plasma Glucose (FPG)
Hide Description Change from baseline in FPG after 26 weeks of treatment
Time Frame Week 0, week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised subjects and missing data was imputed using LOCF. For 6 subjects FPG values were missing.
Arm/Group Title IDeg Placebo
Hide Arm/Group Description:
Liraglutide treatment was initiated on 0.6 mg daily for one week and increased further after the second week in the run-in period. In the randomized period, Insulin degludec (IDeg, 100 U/mL, in a 3 mL prefilled pen PDS290) treatment was recommended to be initiated and administered subcutaneously (under the skin) once daily (OD) with 10 units. After that it was titrated once weekly. If one or more of the pre-breakfast plasma glucose values were below a certain range, the subjects were to reduce the insulin dose. Subjects continued on metformin (1500/day) treatment at the stable, pre-trial dose and maintained dosing frequency levels throughout the trial period.
Placebo treatment (3 mL prefilled pen) in combination with Liraglutide (Lira,1.8 mg/daily, 3 mL prefilled pen) once daily was given subcutaneously (under the skin) in the thigh, abdomen or upper arm (deltoid) at any time of the day according to the subject’s choice for 26 weeks of treatment period. Subjects continued on metformin (1500/day) treatment at the stable, pre-trial dose and maintained dosing frequency levels throughout the trial period.
Overall Number of Participants Analyzed 172 168
Mean (Standard Deviation)
Unit of Measure: mmol/L
-2.60  (2.91) -0.28  (2.44)
3.Secondary Outcome
Title Number of Responders for HbA1c (Below 7.0 %)
Hide Description Number of responders for HbA1c below 7.0%, after 26 weeks of randomised treatment.
Time Frame After 26 weeks of randomised treatment.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised subjects and missing data was imputed using LOCF.
Arm/Group Title IDeg Placebo
Hide Arm/Group Description:
Liraglutide treatment was initiated on 0.6 mg daily for one week and increased further after the second week in the run-in period. In the randomized period, Insulin degludec (IDeg, 100 U/mL, in a 3 mL prefilled pen PDS290) treatment was recommended to be initiated and administered subcutaneously (under the skin) once daily (OD) with 10 units. After that it was titrated once weekly. If one or more of the pre-breakfast plasma glucose values were below a certain range, the subjects were to reduce the insulin dose. Subjects continued on metformin (1500/day) treatment at the stable, pre-trial dose and maintained dosing frequency levels throughout the trial period.
Placebo treatment (3 mL prefilled pen) in combination with Liraglutide (Lira,1.8 mg/daily, 3 mL prefilled pen) once daily was given subcutaneously (under the skin) in the thigh, abdomen or upper arm (deltoid) at any time of the day according to the subject’s choice for 26 weeks of treatment period. Subjects continued on metformin (1500/day) treatment at the stable, pre-trial dose and maintained dosing frequency levels throughout the trial period.
Overall Number of Participants Analyzed 174 172
Measure Type: Number
Unit of Measure: percentage (%) of subjects
77.6 35.5
4.Secondary Outcome
Title Change From Baseline in Mean Pre-breakfast Measurements Used for Titration
Hide Description Change from baseline after 26 weeks of treatment in the average of the pre-breakfast self measured plasma glucose (SMPG) measured on the day of the contact and the two days immediately prior to the contact. The least squares means presented are the estimated values after 26 weeks of treatment and the statistical analysis presents the treatment difference of the change from baseline values as the model is adjusted for baseline.
Time Frame Week 0, week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised subjects and missing data was imputed using LOCF. For 8 subjects the baseline values were missing
Arm/Group Title IDeg Placebo
Hide Arm/Group Description:
Liraglutide treatment was initiated on 0.6 mg daily for one week and increased further after the second week in the run-in period. In the randomized period, Insulin degludec (IDeg, 100 U/mL, in a 3 mL prefilled pen PDS290) treatment was recommended to be initiated and administered subcutaneously (under the skin) once daily (OD) with 10 units. After that it was titrated once weekly. If one or more of the pre-breakfast plasma glucose values were below a certain range, the subjects were to reduce the insulin dose. Subjects continued on metformin (1500/day) treatment at the stable, pre-trial dose and maintained dosing frequency levels throughout the trial period.
Placebo treatment (3 mL prefilled pen) in combination with Liraglutide (Lira,1.8 mg/daily, 3 mL prefilled pen) once daily was given subcutaneously (under the skin) in the thigh, abdomen or upper arm (deltoid) at any time of the day according to the subject’s choice for 26 weeks of treatment period. Subjects continued on metformin (1500/day) treatment at the stable, pre-trial dose and maintained dosing frequency levels throughout the trial period.
Overall Number of Participants Analyzed 171 167
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
5.88  (0.14) 8.23  (0.15)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection IDeg, Placebo
Comments The pre-breakfast measures of SMPG values after 26 weeks of treatment were analysed an ANOVA method with treatment, region and sex as fixed effects, and age and baseline response as covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.34
Confidence Interval (2-Sided) 95%
-2.67 to -2.01
Estimation Comments The treatment contrast estimated was IDeg - Placebo.
5.Secondary Outcome
Title Change From Baseline in 8-point Profile
Hide Description The change from baseline in the 8-point SMPG profile after 26 weeks of randomised treatment. The least squares means presented are the estimated values after 26 weeks of treatment and the statistical analysis presents the treatment difference of the change from baseline values as the model is adjusted for baseline.
Time Frame Week 0, week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised subjects. The subjects not analysed were 12, 45, 46, 44, 44, 54, 56 and 21 subjects for before breakfast, 90 mins after breakfast, before lunch, 90 mins after start of lunch, before main evening meal, 90 mins after main evening meal, before bedtime and before breakfast the following day time points respectively.
Arm/Group Title IDeg Placebo
Hide Arm/Group Description:
Liraglutide treatment was initiated on 0.6 mg daily for one week and increased further after the second week in the run-in period. In the randomized period, Insulin degludec (IDeg, 100 U/mL, in a 3 mL prefilled pen PDS290) treatment was recommended to be initiated and administered subcutaneously (under the skin) once daily (OD) with 10 units. After that it was titrated once weekly. If one or more of the pre-breakfast plasma glucose values were below a certain range, the subjects were to reduce the insulin dose. Subjects continued on metformin (1500/day) treatment at the stable, pre-trial dose and maintained dosing frequency levels throughout the trial period.
Placebo treatment (3 mL prefilled pen) in combination with Liraglutide (Lira,1.8 mg/daily, 3 mL prefilled pen) once daily was given subcutaneously (under the skin) in the thigh, abdomen or upper arm (deltoid) at any time of the day according to the subject’s choice for 26 weeks of treatment period. Subjects continued on metformin (1500/day) treatment at the stable, pre-trial dose and maintained dosing frequency levels throughout the trial period.
Overall Number of Participants Analyzed 172 169
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
Before breakfast, N=170, 164 5.85  (0.15) 8.54  (0.16)
90 min after breakfast, N=153, 148 7.65  (0.24) 9.75  (0.25)
Before lunch, N=151,149 6.33  (0.18) 8.34  (0.19)
90 min after lunch, N=152,150 7.73  (0.21) 9.67  (0.21)
Before evening meal, N=154,148 6.77  (0.20) 9.51  (0.21)
90 mins after evening meal, N=147,145 7.93  (0.21) 9.65  (0.22)
Before bedtime, N=148, 142 7.21  (0.20) 8.95  (0.21)
Before breakfast the next day, N=164,161 6.05  (0.17) 8.55  (0.18)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection IDeg, Placebo
Comments The 8-point profile (SMPG) values after 26 weeks of treatment were analysed jointly using a linear mixed model with an un-structured residual covariance structure and with treatment, time-point and an interaction between treatment and time-point, region and sex as fixed effects, and age and baseline response per time-point as covariates. Missing data was imputed using LOCF. The treatment contrast estimated was IDeg – Placebo for the time point before breakfast.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.69
Confidence Interval (2-Sided) 95%
-3.04 to -2.34
Estimation Comments The treatment contrast estimated was IDeg - Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection IDeg, Placebo
Comments The 8-point profile (SMPG) values after 26 weeks of treatment were analysed jointly using a linear mixed model with an un-structured residual covariance structure and with treatment, time-point and an interaction between treatment and time-point, region and sex as fixed effects, and age and baseline response per time-point as covariates. Missing data was imputed using LOCF. The treatment contrast estimated was IDeg – Placebo for the time point 90 mins after breakfast.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.09
Confidence Interval (2-Sided) 95%
-2.71 to -1.48
Estimation Comments The treatment contrast estimated was IDeg - Placebo.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection IDeg, Placebo
Comments The 8-point profile (SMPG) values after 26 weeks of treatment were analysed jointly using a linear mixed model with an un-structured residual covariance structure and with treatment, time-point and an interaction between treatment and time-point, region and sex as fixed effects, and age and baseline response per time-point as covariates. Missing data was imputed using LOCF. The treatment contrast estimated was IDeg – Placebo for the time point before lunch.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.01
Confidence Interval (2-Sided) 95%
-2.47 to -1.56
Estimation Comments The treatment contrast estimated was IDeg - Placebo.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection IDeg, Placebo
Comments The 8-point profile (SMPG) values after 26 weeks of treatment were analysed jointly using a linear mixed model with an un-structured residual covariance structure and with treatment, time-point and an interaction between treatment and time-point, region and sex as fixed effects, and age and baseline response per time-point as covariates. Missing data was imputed using LOCF. The treatment contrast estimated was IDeg – Placebo for the time point 90 mins after start of lunch.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -1.93
Confidence Interval (2-Sided) 95%
-2.46 to -1.40
Estimation Comments The treatment contrast estimated was IDeg - Placebo.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection IDeg, Placebo
Comments The 8-point profile (SMPG) values after 26 weeks of treatment were analysed jointly using a linear mixed model with an un-structured residual covariance structure and with treatment, time-point and an interaction between treatment and time-point, region and sex as fixed effects, and age and baseline response per time-point as covariates. Missing data was imputed using LOCF. The treatment contrast estimated was IDeg – Placebo for the time point main evening meal.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.74
Confidence Interval (2-Sided) 95%
-2.25 to -1.23
Estimation Comments The treatment contrast estimated was IDeg - Placebo.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection IDeg, Placebo
Comments The 8-point profile (SMPG) values after 26 weeks of treatment were analysed jointly using a linear mixed model with an un-structured residual covariance structure and with treatment, time-point and an interaction between treatment and time-point, region and sex as fixed effects, and age and baseline response per time-point as covariates. Missing data was imputed using LOCF. The treatment contrast estimated was IDeg – Placebo for the time point 90 mins after main evening meal.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.72
Confidence Interval (2-Sided) 95%
-2.26 to -1.18
Estimation Comments The treatment contrast estimated was IDeg - Placebo.
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection IDeg, Placebo
Comments The 8-point profile (SMPG) values after 26 weeks of treatment were analysed jointly using a linear mixed model with an un-structured residual covariance structure and with treatment, time-point and an interaction between treatment and time-point, region and sex as fixed effects, and age and baseline response per time-point as covariates. Missing data was imputed using LOCF. The treatment contrast estimated was IDeg – Placebo for the time point before bedtime.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.75
Confidence Interval (2-Sided) 95%
-2.27 to -1.23
Estimation Comments The treatment contrast estimated was IDeg - Placebo.
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection IDeg, Placebo
Comments The 8-point profile (SMPG) values after 26 weeks of treatment were analysed jointly using a linear mixed model with an un-structured residual covariance structure and with treatment, time-point and an interaction between treatment and time-point, region and sex as fixed effects, and age and baseline response per time-point as covariates. Missing data was imputed using LOCF. The treatment contrast estimated was IDeg – Placebo for the time point before breakfast the following day.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.50
Confidence Interval (2-Sided) 95%
-2.91 to -2.09
Estimation Comments The treatment contrast estimated was IDeg - Placebo.
6.Secondary Outcome
Title Change From Baseline in Mean of the 8-point Profile
Hide Description Change from baseline in mean of the 8-point profile after 26 weeks of randomised treatment.
Time Frame Week 0, week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised subjects and missing data is imputed using LOCF. Mean values were missing for 11 subjects.
Arm/Group Title IDeg Placebo
Hide Arm/Group Description:
Liraglutide treatment was initiated on 0.6 mg daily for one week and increased further after the second week in the run-in period. In the randomized period, Insulin degludec (IDeg, 100 U/mL, in a 3 mL prefilled pen PDS290) treatment was recommended to be initiated and administered subcutaneously (under the skin) once daily (OD) with 10 units. After that it was titrated once weekly. If one or more of the pre-breakfast plasma glucose values were below a certain range, the subjects were to reduce the insulin dose. Subjects continued on metformin (1500/day) treatment at the stable, pre-trial dose and maintained dosing frequency levels throughout the trial period.
Placebo treatment (3 mL prefilled pen) in combination with Liraglutide (Lira,1.8 mg/daily, 3 mL prefilled pen) once daily was given subcutaneously (under the skin) in the thigh, abdomen or upper arm (deltoid) at any time of the day according to the subject’s choice for 26 weeks of treatment period. Subjects continued on metformin (1500/day) treatment at the stable, pre-trial dose and maintained dosing frequency levels throughout the trial period.
Overall Number of Participants Analyzed 169 166
Mean (Standard Deviation)
Unit of Measure: mmol/L
-2.3  (1.8) -0.5  (1.7)
7.Secondary Outcome
Title Number of Hypoglycaemic Episodes
Hide Description Number of confirmed hypoglycaemic episodes from week 0 to 26 weeks of randomised treatment. A hypoglycaemic episode was defined as treatment emergent if the onset of the episode occurred after the first administration of investigational medicinal product and no later than 7 days after the last day on trial product. Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia or minor hypoglycaemic episodes.
Time Frame Weeks 0 - 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set (SAS) included all subjects who received at least one dose of the investigational product or its comparator.
Arm/Group Title IDeg Placebo
Hide Arm/Group Description:
Liraglutide treatment was initiated on 0.6 mg daily for one week and increased further after the second week in the run-in period. In the randomized period, Insulin degludec (IDeg, 100 U/mL, in a 3 mL prefilled pen PDS290) treatment was recommended to be initiated and administered subcutaneously (under the skin) once daily (OD) with 10 units. After that it was titrated once weekly. If one or more of the pre-breakfast plasma glucose values were below a certain range, the subjects were to reduce the insulin dose. Subjects continued on metformin (1500/day) treatment at the stable, pre-trial dose and maintained dosing frequency levels throughout the trial period.
Placebo treatment (3 mL prefilled pen) in combination with Liraglutide (Lira,1.8 mg/daily, 3 mL prefilled pen) once daily was given subcutaneously (under the skin) in the thigh, abdomen or upper arm (deltoid) at any time of the day according to the subject’s choice for 26 weeks of treatment period. Subjects continued on metformin (1500/day) treatment at the stable, pre-trial dose and maintained dosing frequency levels throughout the trial period.
Overall Number of Participants Analyzed 173 170
Measure Type: Number
Unit of Measure: events
47 9
8.Secondary Outcome
Title Number of Adverse Events
Hide Description Number of treatment emergent AEs (TEAEs) from week 0 to week 26 of the randomised treatment. A TEAE was defined as an event that had onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment.
Time Frame Weeks 0 - 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The SAS included all subjects who received at least one dose of the investigational product or its comparator.
Arm/Group Title IDeg Placebo
Hide Arm/Group Description:
Liraglutide treatment was initiated on 0.6 mg daily for one week and increased further after the second week in the run-in period. In the randomized period, Insulin degludec (IDeg, 100 U/mL, in a 3 mL prefilled pen PDS290) treatment was recommended to be initiated and administered subcutaneously (under the skin) once daily (OD) with 10 units. After that it was titrated once weekly. If one or more of the pre-breakfast plasma glucose values were below a certain range, the subjects were to reduce the insulin dose. Subjects continued on metformin (1500/day) treatment at the stable, pre-trial dose and maintained dosing frequency levels throughout the trial period.
Placebo treatment (3 mL prefilled pen) in combination with Liraglutide (Lira,1.8 mg/daily, 3 mL prefilled pen) once daily was given subcutaneously (under the skin) in the thigh, abdomen or upper arm (deltoid) at any time of the day according to the subject’s choice for 26 weeks of treatment period. Subjects continued on metformin (1500/day) treatment at the stable, pre-trial dose and maintained dosing frequency levels throughout the trial period.
Overall Number of Participants Analyzed 173 170
Measure Type: Number
Unit of Measure: events
285 252
9.Secondary Outcome
Title Change From Baseline in Patient Reported Health-related Quality of Life Using the Short-Form 36 Health Survey Version 2 (SF-36®v2)
Hide Description Change in subject’s quality of life was evaluated using the Short-Form 36 Health Survey version 2 (SF-36®v2). Evaluations were performed at baseline and at the last treatment visit (week 26). SF-36 was assessed on a scale range of 0.65 to 80.73 for physical health and -8.81 to 81.65 for mental health respectively, where higher scores indicated a better quality of life. 0-100 scores from the SF-36 were converted to a norm-based score using a T-score transformation in order to obtain a direct interpretation in relation to the distribution of the scores in the 1998 U.S. general population.
Time Frame Week 0, week 26
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The FAS included all randomised subjects and missing data was imputed using LOCF. For 3 subjects PRO scores were missing at the baseline and did not contribute to the analysis.
Arm/Group Title IDeg Placebo
Hide Arm/Group Description:
Liraglutide treatment was initiated on 0.6 mg daily for one week and increased further after the second week in the run-in period. In the randomized period, Insulin degludec (IDeg, 100 U/mL, in a 3 mL prefilled pen PDS290) treatment was recommended to be initiated and administered subcutaneously (under the skin) once daily (OD) with 10 units. After that it was titrated once weekly. If one or more of the pre-breakfast plasma glucose values were below a certain range, the subjects were to reduce the insulin dose. Subjects continued on metformin (1500/day) treatment at the stable, pre-trial dose and maintained dosing frequency levels throughout the trial period.
Placebo treatment (3 mL prefilled pen) in combination with Liraglutide (Lira,1.8 mg/daily, 3 mL prefilled pen) once daily was given subcutaneously (under the skin) in the thigh, abdomen or upper arm (deltoid) at any time of the day according to the subject’s choice for 26 weeks of treatment period. Subjects continued on metformin (1500/day) treatment at the stable, pre-trial dose and maintained dosing frequency levels throughout the trial period.
Overall Number of Participants Analyzed 174 169
Mean (Standard Deviation)
Unit of Measure: T-scores
Physical health 0.5  (6.3) 0.0  (6.2)
Mental health 0.6  (8.1) -0.7  (8.8)
Time Frame The adverse events were collected in a time frame of 26 weeks + 7 days follow up. Adverse event with an onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment.
Adverse Event Reporting Description The SAS included all subjects who received at least one dose of the investigational product or its comparator.
 
Arm/Group Title IDeg Placebo
Hide Arm/Group Description Liraglutide treatment was initiated on 0.6 mg daily for one week and increased further after the second week in the run-in period. In the randomized period, Insulin degludec (IDeg, 100 U/mL, in a 3 mL prefilled pen PDS290) treatment was recommended to be initiated and administered subcutaneously (under the skin) once daily (OD) with 10 units. After that it was titrated once weekly. If one or more of the pre-breakfast plasma glucose values were below a certain range, the subjects were to reduce the insulin dose. Subjects continued on metformin (1500/day) treatment at the stable, pre-trial dose and maintained dosing frequency levels throughout the trial period. Placebo treatment (3 mL prefilled pen) in combination with Liraglutide (Lira,1.8 mg/daily, 3 mL prefilled pen) once daily was given subcutaneously (under the skin) in the thigh, abdomen or upper arm (deltoid) at any time of the day according to the subject’s choice for 26 weeks of treatment period. Subjects continued on metformin (1500/day) treatment at the stable, pre-trial dose and maintained dosing frequency levels throughout the trial period.
All-Cause Mortality
IDeg Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
IDeg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/173 (3.47%)      9/170 (5.29%)    
Cardiac disorders     
Atrial fibrillation  1  0/173 (0.00%)  0 1/170 (0.59%)  1
Cardiac failure  1  0/173 (0.00%)  0 1/170 (0.59%)  1
Cardiac failure congestive  1  0/173 (0.00%)  0 1/170 (0.59%)  1
Tachycardia  1  0/173 (0.00%)  0 1/170 (0.59%)  1
Ventricular tachycardia  1  0/173 (0.00%)  0 1/170 (0.59%)  1
Gastrointestinal disorders     
Abdominal hernia  1  1/173 (0.58%)  1 0/170 (0.00%)  0
Gastritis erosive  1  1/173 (0.58%)  1 0/170 (0.00%)  0
Infections and infestations     
Upper respiratory tract infection  1  0/173 (0.00%)  0 1/170 (0.59%)  1
Urosepsis  1  0/173 (0.00%)  0 1/170 (0.59%)  1
Injury, poisoning and procedural complications     
Humerus fracture  1  0/173 (0.00%)  0 1/170 (0.59%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Lentigo maligna stage II  1  1/173 (0.58%)  1 0/170 (0.00%)  0
Malignant melanoma  1  0/173 (0.00%)  0 1/170 (0.59%)  1
Transitional cell carcinoma  1  0/173 (0.00%)  0 1/170 (0.59%)  1
Respiratory, thoracic and mediastinal disorders     
Pleural effusion  1  0/173 (0.00%)  0 1/170 (0.59%)  1
Surgical and medical procedures     
Cholecystectomy  1  1/173 (0.58%)  1 0/170 (0.00%)  0
Diabetes mellitus management  1  1/173 (0.58%)  1 0/170 (0.00%)  0
Medical device removal  1  1/173 (0.58%)  1 0/170 (0.00%)  0
Vascular disorders     
Aortic stenosis  1  1/173 (0.58%)  1 0/170 (0.00%)  0
Femoral artery occlusion  1  1/173 (0.58%)  1 0/170 (0.00%)  0
Peripheral artery stenosis  1  1/173 (0.58%)  1 0/170 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
IDeg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   33/173 (19.08%)      32/170 (18.82%)    
Gastrointestinal disorders     
Diarrhoea  1  10/173 (5.78%)  10 13/170 (7.65%)  17
Infections and infestations     
Nasopharyngitis  1  14/173 (8.09%)  15 11/170 (6.47%)  12
Investigations     
Lipase increased  1  10/173 (5.78%)  11 13/170 (7.65%)  15
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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. Any such communication must be submitted in writing to the Novo Nordisk trial manager prior to submission for comments. Comments will be given within four weeks from receipt of the planned communication.
Results Point of Contact
Name/Title: Public Access to Clinical Trials
Organization: Novo Nordisk A/S
Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT01664247     History of Changes
Other Study ID Numbers: NN1250-3944
2011-004665-32 ( EudraCT Number )
U1111-1124-6612 ( Other Identifier: WHO )
First Submitted: August 10, 2012
First Posted: August 14, 2012
Results First Submitted: October 23, 2015
Results First Posted: April 20, 2016
Last Update Posted: September 25, 2017