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A Trial Comparing the Efficacy and Safety of Insulin Degludec/Liraglutide and Insulin Degludec in Subjects With Type 2 Diabetes (DUAL™ II)

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ClinicalTrials.gov Identifier: NCT01392573
Recruitment Status : Completed
First Posted : July 12, 2011
Results First Posted : January 20, 2017
Last Update Posted : January 3, 2019
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/liraglutide
Drug: insulin degludec
Enrollment 413
Recruitment Details The trial was conducted at 75 sites in 7 countries: Bulgaria (6), Switzerland (2), Denmark (3), Hungary (3), India (6), Slovenia (3), and the United States (52).
Pre-assignment Details  
Arm/Group Title IDegLira IDeg
Hide Arm/Group Description Insulin degludec/liraglutide (IDegLira) was injected subcutaneously (under the skin) once daily for 26 weeks in combination with metformin treatment. Metformin dose was maintained at the stable, pre-randomisation dose and frequency level. Treatment with IDegLira was initiated at 16 dose steps containing 16 units insulin degludec and 0.6 mg liraglutide. Dose adjustment of IDegLira was to be performed twice weekly based on the mean of three pre-breakfast self-monitored plasma glucose (SMPG) values measured on the day of titration and the two days prior to titration aiming at a fasting glycaemic target of 4.0-5.0 mmol/L. Insulin degludec (IDeg) was injected subcutaneously (under the skin) once daily for 26 weeks. Metformin dose was maintained at the stable, pre-randomisation dose and frequency level. Treatment with IDeg was initiated with 16 units. Dose adjustment of IDeg was to be performed twice weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0−5.0 mmol/L).
Period Title: Overall Study
Started 207 206
Exposed 207 206
Completed 175 171
Not Completed 32 35
Reason Not Completed
Adverse Event             1             3
Lack of Efficacy             1             2
Protocol Violation             0             2
Withdrawal Criteria             13             15
Site closure             8             7
Unclassified             9             6
Arm/Group Title IDegLira IDeg Total
Hide Arm/Group Description IDegLira was injected subcutaneously (under the skin) once daily for 26 weeks in combination with metformin treatment. Metformin dose was maintained at the stable, pre-randomisation dose and frequency level. Treatment with IDegLira was initiated at 16 dose steps containing 16 units insulin degludec and 0.6 mg liraglutide. Dose adjustment of IDegLira was to be performed twice weekly based on the mean of three pre-breakfast SMPG values measured on the day of titration and the two days prior to titration aiming at a fasting glycaemic target of 4.0-5.0 mmol/L. Insulin degludec (IDeg) was injected subcutaneously (under the skin) once daily for 26 weeks. Metformin dose was maintained at the stable, pre-randomisation dose and frequency level. Treatment with IDeg was initiated with 16 units. Dose adjustment of IDeg was to be performed twice weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0−5.0 mmol/L). Total of all reporting groups
Overall Number of Baseline Participants 199 199 398
Hide Baseline Analysis Population Description
Full analysis set (FAS) included all randomised subjects except 15 subjects (8 in IDegLira arm and 7 in IDeg arm) that were excluded due to site closure.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 199 participants 199 participants 398 participants
56.8  (8.9) 57.5  (10.5) 57.2  (9.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 199 participants 199 participants 398 participants
Female
87
  43.7%
93
  46.7%
180
  45.2%
Male
112
  56.3%
106
  53.3%
218
  54.8%
HbA1c (glycosylated haemoglobin)  
Mean (Standard Deviation)
Unit of measure:  Percentage of glycosylated haemoglobin
Number Analyzed 199 participants 199 participants 398 participants
8.7  (0.7) 8.8  (0.7) 8.8  (0.7)
Body Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 199 participants 199 participants 398 participants
95.4  (19.4) 93.5  (20.0) 94.5  (19.7)
1.Primary Outcome
Title Change From Baseline in HbA1c (Glycosylated Haemoglobin)
Hide Description Observed mean change from baseline in HbA1c after 26 Weeks of treatment.
Time Frame Week 0, week 26
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Missing data was imputed using last observation carried forward (LOCF).
Arm/Group Title IDegLira IDeg
Hide Arm/Group Description:
IDegLira was injected subcutaneously (under the skin) once daily for 26 weeks in combination with metformin treatment. Metformin dose was maintained at the stable, pre-randomisation dose and frequency level. Treatment with IDegLira was initiated at 16 dose steps containing 16 units insulin degludec and 0.6 mg liraglutide. Dose adjustment of IDegLira was to be performed twice weekly based on the mean of three pre-breakfast SMPG values measured on the day of titration and the two days prior to titration aiming at a fasting glycaemic target of 4.0-5.0 mmol/L.
Insulin degludec (IDeg) was injected subcutaneously (under the skin) once daily for 26 weeks. Metformin dose was maintained at the stable, pre-randomisation dose and frequency level. Treatment with IDeg was initiated with 16 units. Dose adjustment of IDeg was to be performed twice weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0−5.0 mmol/L).
Overall Number of Participants Analyzed 199 199
Mean (Standard Deviation)
Unit of Measure: percentage of glycosylated haemoglobin
-1.90  (1.09) -0.89  (1.18)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection IDegLira, IDeg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments ANCOVA model with treatment, country and previous antidiabetic treatment as fixed effects and baseline HbA1c value as covariate
Method of Estimation Estimation Parameter Treatment contrast
Estimated Value -1.05
Confidence Interval (2-Sided) 95%
-1.25 to -0.84
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change in Body Weight
Hide Description Observed mean change from baseline in body weight after 26 Weeks of treatment.
Time Frame Week 0, week 26
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set. Missing data was imputed using LOCF.
Arm/Group Title IDegLira IDeg
Hide Arm/Group Description:
IDegLira was injected subcutaneously (under the skin) once daily for 26 weeks in combination with metformin treatment. Metformin dose was maintained at the stable, pre-randomisation dose and frequency level. Treatment with IDegLira was initiated at 16 dose steps containing 16 units insulin degludec and 0.6 mg liraglutide. Dose adjustment of IDegLira was to be performed twice weekly based on the mean of three pre-breakfast SMPG values measured on the day of titration and the two days prior to titration aiming at a fasting glycaemic target of 4.0-5.0 mmol/L.
Insulin degludec (IDeg) was injected subcutaneously (under the skin) once daily for 26 weeks. Metformin dose was maintained at the stable, pre-randomisation dose and frequency level. Treatment with IDeg was initiated with 16 units. Dose adjustment of IDeg was to be performed twice weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0−5.0 mmol/L).
Overall Number of Participants Analyzed 199 199
Mean (Standard Deviation)
Unit of Measure: kg
-2.7  (3.7) 0.0  (3.4)
Time Frame Adverse events were captured from the time of consent untill 26 weeks of treatment, and were followed-up for 7 days after the final visit (upto overall 27 weeks).
Adverse Event Reporting Description Safety analysis set included all subjects receiving at least one dose of the investigational product or comparator except 15 subjects (8 in IDegLira arm and 7 in IDeg arm) that were excluded due to site closure. Subjects in the safety analysis set contributed to the evaluation “as treated”.
 
Arm/Group Title IDegLira IDeg
Hide Arm/Group Description IDegLira was injected subcutaneously (under the skin) once daily for 26 weeks in combination with metformin treatment. Metformin dose was maintained at the stable, pre-randomisation dose and frequency level. Treatment with IDegLira was initiated at 16 dose steps containing 16 units insulin degludec and 0.6 mg liraglutide. Dose adjustment of IDegLira was to be performed twice weekly based on the mean of three pre-breakfast SMPG values measured on the day of titration and the two days prior to titration aiming at a fasting glycaemic target of 4.0-5.0 mmol/L. Insulin degludec (IDeg) was injected subcutaneously (under the skin) once daily for 26 weeks. Metformin dose was maintained at the stable, pre-randomisation dose and frequency level. Treatment with IDeg was initiated with 16 units. Dose adjustment of IDeg was to be performed twice weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0−5.0 mmol/L).
All-Cause Mortality
IDegLira IDeg
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
IDegLira IDeg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   7/199 (3.52%)      11/199 (5.53%)    
Cardiac disorders     
Acute myocardial infarction  1  1/199 (0.50%)  1 1/199 (0.50%)  1
Atrial fibrillation  1  1/199 (0.50%)  1 0/199 (0.00%)  0
Ventricular fibrillation  1  1/199 (0.50%)  1 0/199 (0.00%)  0
Ventricular tachycardia  1  1/199 (0.50%)  1 0/199 (0.00%)  0
Hepatobiliary disorders     
Cholecystitis acute  1  1/199 (0.50%)  1 0/199 (0.00%)  0
Infections and infestations     
Pneumonia  1  1/199 (0.50%)  1 1/199 (0.50%)  1
Vestibular neuronitis  1  1/199 (0.50%)  1 0/199 (0.00%)  0
Injury, poisoning and procedural complications     
Acetabulum fracture  1  0/199 (0.00%)  0 1/199 (0.50%)  1
Foot fracture  1  0/199 (0.00%)  0 1/199 (0.50%)  1
Humerus fracture  1  0/199 (0.00%)  0 1/199 (0.50%)  1
Metabolism and nutrition disorders     
Hypoglycaemia  1  1/199 (0.50%)  1 0/199 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Intervertebral disc protrusion  1  0/199 (0.00%)  0 1/199 (0.50%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Pancreatic carcinoma metastatic  1  0/199 (0.00%)  0 1/199 (0.50%)  1
Nervous system disorders     
Convulsion  1  0/199 (0.00%)  0 1/199 (0.50%)  1
Ischaemic stroke  1  0/199 (0.00%)  0 1/199 (0.50%)  1
Mononeuropathy  1  0/199 (0.00%)  0 1/199 (0.50%)  1
VIIth nerve paralysis  1  1/199 (0.50%)  1 0/199 (0.00%)  0
Vertigo CNS origin  1  0/199 (0.00%)  0 1/199 (0.50%)  1
Psychiatric disorders     
Major depression  1  1/199 (0.50%)  1 0/199 (0.00%)  0
Renal and urinary disorders     
Renal failure acute  1  1/199 (0.50%)  1 0/199 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Asthma  1  0/199 (0.00%)  0 1/199 (0.50%)  1
Surgical and medical procedures     
Coronary revascularisation  1  0/199 (0.00%)  0 1/199 (0.50%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA version 15.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
IDegLira IDeg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   45/199 (22.61%)      29/199 (14.57%)    
Gastrointestinal disorders     
Diarrhoea  1  13/199 (6.53%)  21 7/199 (3.52%)  8
Nausea  1  13/199 (6.53%)  20 7/199 (3.52%)  7
Infections and infestations     
Nasopharyngitis  1  5/199 (2.51%)  5 12/199 (6.03%)  14
Investigations     
Lipase increased  1  12/199 (6.03%)  12 7/199 (3.52%)  7
Nervous system disorders     
Headache  1  12/199 (6.03%)  23 4/199 (2.01%)  6
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA version 15.0
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.
At the end of the trial, one or more scientific publications 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.
Results Point of Contact
Name/Title: Global Clinical Registry (GCR, 1452)
Organization: Novo Nordisk A/S
Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT01392573     History of Changes
Other Study ID Numbers: NN9068-3912
2011-002336-72 ( EudraCT Number )
U1111-1121-4897 ( Other Identifier: WHO )
First Submitted: July 7, 2011
First Posted: July 12, 2011
Results First Submitted: November 23, 2016
Results First Posted: January 20, 2017
Last Update Posted: January 3, 2019