Back to resultsA Double-blinded Trial Comparing the Efficacy and Safety of Insulin Degludec/Liraglutide and Insulin Degludec Both in Combination With Metformin in Japanese Subjects With Type 2 Diabetes Mellitus Inadequately Controlled With Basal or Pre-mix/Combination Insulin Therapy and Oral Anti-diabetic Drugs (DUAL™ II Japan)
Primary Purpose
Diabetes, Diabetes Mellitus, Type 2
Status
Completed
Phase
Phase 3
Locations
Japan
Study Type
Interventional
Intervention
Insulin degludec/liraglutide
Insulin degludec
Sponsored by
About this trial
This is an interventional treatment trial for Diabetes
Eligibility Criteria
Inclusion Criteria:
- Male or female Japanese subjects, age at least 20 years at the time of signing informed consent
- T2DM (type 2 diabetes mellitus) subjects (diagnosed clinically) for at least 6 months prior to screening
- HbA1c (glycosylated haemoglobin) 7.5-11.0 per cent [58 mmol/mol-97 mmol/mol] (both inclusive) by central laboratory analysis
- Subjects on stable daily insulin doses for at least 60 days prior to screening administered once or twice daily, either as basal insulin (e.g. IDeg, insulin glargine, insulin detemir, NPH insulin) or pre-mix/combination insulin (e.g. biphasic insulin aspart, insulin degludec/insulin aspart). Total daily insulin dose in the previous 60 days should be within 20-50 units, both inclusive, and on the day of screening, but fluctuations of plus/minus 20 per cent within the 60 days prior to screening are acceptable. The specified insulin treatment should be administered in combination with a stable daily dose of metformin within current approved Japanese label for at least 60 days prior to screening - additionally, the anti-diabetic treatment can be with or without a stable daily dose of one of the following other OADs (oral anti-diabetic drug): SU (sulfonylureas), glinides, alpha-glucosidase inhibitor, SGLT2i (sodium glucose co-transporter 2 inhibitor) or TZD (thiazolidinedione) within current approved Japanese label for at least 60 days prior to screening
- Body Mass Index (BMI) equal or above 23 kg/m^2
Exclusion Criteria:
- Receipt of any investigational medicinal product (IMP) within 30 days before screening
- Use of any anti-diabetic drug in a period of 60 days before screening (except premix/ combination or basal insulin, metformin, SU, glinides, α-GI, SGLT2i, or TZD) or anticipated change in concomitant medication, which in the investigators opinion could interfere with glucose metabolism (e.g. systemic corticosteroids or bolus insulin)
- Treatment with glucagon-like peptide-1 (GLP-1) receptor agonist during the last 60 days prior to screening and furthermore, the discontinuation of GLP-1 receptor agonist at any point in time must not have been due to safety concerns, tolerability issues or lack of efficacy, as judged by the investigator
- Treatment with dipetidyl peptidase-4 (DPP-4) inhibitors during the last 60 days prior to screening - Impaired liver function, defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) equal or above 2.5 times upper limit of normal
- Renal impairment estimated Glomerular Filtration Rate (eGFR) below 60 mL/min/1.73m^2 as per Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
- Screening calcitonin equal or above 50 ng/L
- History of pancreatitis (acute or chronic)
- Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN 2)
- Subjects presently classified as being in New York Heart Association (NYHA) Class IV
Sites / Locations
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
- Novo Nordisk Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Insulin degludec/liraglutide
Insulin degludec
Arm Description
Outcomes
Primary Outcome Measures
Change in Glycosylated Haemoglobin (HbA1c)
Change from baseline (week 0) in HbA1c after 26 weeks of treatment.
Secondary Outcome Measures
Change in Body Weight
Change from baseline (week 0) in body weight after 26 weeks of treatment.
Change in Fasting Plasma Glucose (FPG)
Change from baseline (week 0) in FPG after 26 weeks of treatment.
Number of Treatment Emergent Severe or Blood Glucose (BG) Confirmed Hypoglycaemic Episodes
Treatment emergent hypoglycaemic episode is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.
Severe or BG confirmed hypoglycaemic episodes were defined as episodes that were severe according to the American Diabetes Association (ADA) classification or BG confirmed by a plasma glucose value < 3.1 mmol/L (56 mg/dL) with or without symptoms consistent with hypoglycaemia.
Severe hypoglycaemia according to the ADA definition: an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. Plasma glucose concentrations may not be available during an event, but neurological recovery following the return of plasma glucose to normal is considered sufficient evidence that the event was induced by a low plasma glucose concentration.
Daily Insulin Dose
Actual daily total insulin dose after 26 weeks.
Responder (Yes/no): HbA1c Less Than 7.0%
Number of subjects with HbA1c less than 7.0% after 26 weeks.
Responder (Yes/no): HbA1c Less Than 7.0% and Without Weight Gain
Number of subjects with HbA1c less than 7.0% and without weight gain after 26 weeks.
Responder (Yes/no): HbA1c Less Than 7.0% Without Treatment Emergent Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemic Episodes During the Last 12 Weeks of Treatment
Number of subjects with HbA1c less than 7.0% after 26 weeks, who did not experience treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes during the last 12 weeks of treatment.
Treatment emergent hypoglycaemic episode is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.
Severe or BG confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification or BG confirmed by a plasma glucose value < 3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.
Responder (Yes/no): HbA1c Less Than 7.0% and Without Weight Gain and Without Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During the Last 12 Weeks of Treatment
Number of subjects with HbA1c less than 7.0% and no weight gain after 26 weeks, who did not experience treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes during the last 12 weeks of treatment.
Treatment emergent hypoglycaemic episode is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.
Severe or BG confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification or BG confirmed by a plasma glucose value < 3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.
Responder (Yes/no): HbA1c Less Than or Equal to 6.5%
Number of subjects with HbA1c less than or equal to 6.5% after 26 weeks.
Responder (Yes/no): HbA1c Less Than or Equal to 6.5% and Without Weight Gain
Number of subjects with HbA1c less than or equal to 6.5% and without weight gain
Responder (Yes/no): HbA1c Less Than or Equal to 6.5% Without Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During the Last 12 Weeks of Treatment
Number of subjects with HbA1c less than or equal to 6.5% after 26 weeks, who did not experience treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes during the last 12 weeks of treatment.
Treatment emergent hypoglycaemic episode is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.
Severe or BG confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification or BG confirmed by a plasma glucose value < 3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.
Responder (Yes/no): HbA1c Less Than or Equal to 6.5% and Without Weight Gain and Without Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During the Last 12 Weeks of Treatment
Number of subjects with HbA1c less than or equal to 6.5% and no weight gain after 26 weeks, who did not experience treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes during the last 12 weeks of treatment.
Treatment emergent hypoglycaemic episode is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.
Severe or BG confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification or BG confirmed by a plasma glucose value < 3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.
Change in Waist Circumference
Change from baseline (week 0) in waist circumference after 26 weeks of treatment.
Change in Blood Pressure (Systolic and Diastolic)
Change from baseline in blood pressure (systolic and diastolic) after 26 weeks of treatment.
Self-measured Blood Glucose (SMBG) 9-point Profile (Individual Points in the Profile)
Subjects were instructed to measure their plasma glucose at following timepoints: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner, at bedtime, at 4:00 a.m. and before breakfast the following day.
Change in SMBG 9-point Profile: Mean of the 9-point Profile
Subjects were instructed to measure their plasma glucose at following timepoints: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner, at bedtime, at 4:00 a.m. and before breakfast the following day. Mean of the 9-point profile was defined as the area under the profile (calculated using the trapezoidal method) divided by the measurement time.
Change in SMBG 9-point Profile: Mean of Postprandial Plasma Glucose Increments (From Before Meal to 90 Minutes After Breakfast, Lunch and Dinner)
Subjects were instructed to measure their plasma glucose at following timepoints: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner, at bedtime, at 4:00 a.m. and before breakfast the following day. The mean increment over all meals was derived as the mean of all available meal increments.
Fasting Lipid Profile
Lipid profile includes total cholesterol, low density lipoprotein cholesterol (LDL cholesterol), high density lipoprotein cholesterol (HDL cholesterol), very low density lipoprotein cholesterol (VLDL cholesterol), triglycerides and free fatty acids. Lipid profile parameters are represented as ratio to baseline values.
Number of Treatment Emergent Adverse Events (TEAE)
Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. If the event had onset date before the first day of exposure on randomised treatment and increased in severity during the treatment period and until 7 days after the last drug date, then this event was considered as a TEAE.
Number of Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes
Treatment emergent hypoglycaemic episode is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.
Severe or BG confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe according to the American Diabetes Association (ADA) classification or BG confirmed by a plasma glucose value < 3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.
Severe hypoglycaemia according to the ADA definition: an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. Plasma glucose concentrations may not be available during an event, but neurological recovery following the return of plasma glucose to normal is considered sufficient evidence that the event was induced by a low plasma glucose concentration.
Number of Treatment Emergent Hypoglycaemic Episodes According to American Diabetes Association (ADA) Definition
Results represent total number of treatment emergent hypoglycaemic episodes that fall under ADA's definition of hypoglycaemia. ADA's definition of hypoglycaemia includes following categories:
Severe hypoglycaemia
Documented symptomatic hypoglycaemia
Asymptomatic hypoglycaemia
Probable symptomatic hypoglycaemia
Pseudo-hypoglycaemia. Treatment emergent hypoglycaemic episode is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.
Number of Treatment Emergent Nocturnal Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes
Treatment emergent hypoglycaemic episode is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Nocturnal period: The period between 00:01 and 05:59 a.m. (both inclusive).
Severe or BG confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe according to the American Diabetes Association (ADA) classification or BG confirmed by a plasma glucose value < 3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.
Severe hypoglycaemia according to the ADA definition: an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. Plasma glucose concentrations may not be available during an event, but neurological recovery following the return of plasma glucose to normal is considered sufficient evidence that the event was induced by a low plasma glucose concentration.
Change in Clinical Evaluation: Fundoscopy or Fundus Photography
The result of the fundus photography/dilated fundoscopy was interpreted by the investigator into following categories: Normal; Abnormal (Abn), Not Clinically significant (NCS); Abnormal, Clinically significant (CS). Reported results are number of subjects with 'normal'; 'Abn, NCS' and 'Abn, CS' fundoscopy/fundus photography results at screening (week -2 to week 0) and week 26.
Change in Clinical Evaluation: Electrocardiogram (ECG)
The result of the ECG was interpreted by the investigator into following categories: Normal; Abnormal (Abn), Not Clinically significant (NCS); Abnormal, Clinically significant (CS). Reported results are number of subjects with 'normal'; 'Abn, NCS' and 'Abn, CS' ECG results at screening (week -2 to week 0) and week 26.
Change in Pulse
Change in pulse after 26 weeks of treatment.
Change From Baseline in Patient Reported Outcomes (PROs) of Treatment: Diabetes Therapy-Related Quality of Life (DTR-QOL)Questionnaire
For the DTR-QOL questionnaire, change from baseline in the 'Total score' and the following four 'Domain scores' were analysed:
Burden on social activities and daily activities
Anxiety and dissatisfaction with treatment
Hypoglycaemia
Satisfaction with treatment. The scoring range of 'Total score' was converted to 0-100 (best case response = 100; worst case response = 0).
The scoring range for each of four domains was converted to 0-100 (best case response = 100; worst case response = 0).
Change From Baseline in Patient Reported Outcomes (PROs) of Treatment: EuroQol-5D (EQ-5D-5L) Questionnaire
Overall health state was rated by patients using the EQ-5D-5L visual analogue scale (VAS) and the EQ-5D-5L index score. The EQ-5D-5L VAS is a vertical scale where patients can rank their health from 0 (worst health imaginable) to 100 (best health imaginable).
The EQ-5D-5L index score was calculated based on the 5 dimensions, i.e., mobility, self-care, usual activities (e.g., work, study), pain/discomfort and anxiety/depression with five response levels for each dimension, i.e., no problems, slight problems, moderate problems, severe problems and extreme problems. The scores from 5 dimensions are then converted to the EQ-5D-5L index score scale: 0 - 1 (full health/best-case response = 1; death/worst-case response = 0).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02911948
Brief Title
A Double-blinded Trial Comparing the Efficacy and Safety of Insulin Degludec/Liraglutide and Insulin Degludec Both in Combination With Metformin in Japanese Subjects With Type 2 Diabetes Mellitus Inadequately Controlled With Basal or Pre-mix/Combination Insulin Therapy and Oral Anti-diabetic Drugs
Acronym
DUAL™ II Japan
Official Title
A Double-blinded Trial Comparing the Efficacy and Safety of Insulin Degludec/Liraglutide and Insulin Degludec Both in Combination With Metformin in Japanese Subjects With Type 2 Diabetes Mellitus Inadequately Controlled With Basal or Pre-mix/Combination Insulin Therapy and Oral Anti-diabetic Drugs
Study Type
Interventional
2. Study Status
Record Verification Date
March 2021
Overall Recruitment Status
Completed
Study Start Date
September 21, 2016 (Actual)
Primary Completion Date
November 17, 2017 (Actual)
Study Completion Date
November 22, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novo Nordisk A/S
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This trial is conducted in Asia. The aim of this trial is to compare the efficacy and safety of insulin degludec/liraglutide and insulin degludec both in combination with metformin in Japanese subjects with type 2 diabetes mellitus inadequately controlled with basal or pre-mix/combination insulin therapy and oral anti-diabetic drugs.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes, Diabetes Mellitus, Type 2
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
210 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Insulin degludec/liraglutide
Arm Type
Experimental
Arm Title
Insulin degludec
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Insulin degludec/liraglutide
Intervention Description
Injected s.c. / subcutaneously (under the skin) once daily
Intervention Type
Drug
Intervention Name(s)
Insulin degludec
Intervention Description
Injected s.c. / subcutaneously (under the skin) once daily
Primary Outcome Measure Information:
Title
Change in Glycosylated Haemoglobin (HbA1c)
Description
Change from baseline (week 0) in HbA1c after 26 weeks of treatment.
Time Frame
week 0, week 26
Secondary Outcome Measure Information:
Title
Change in Body Weight
Description
Change from baseline (week 0) in body weight after 26 weeks of treatment.
Time Frame
week 0, week 26
Title
Change in Fasting Plasma Glucose (FPG)
Description
Change from baseline (week 0) in FPG after 26 weeks of treatment.
Time Frame
week 0, week 26
Title
Number of Treatment Emergent Severe or Blood Glucose (BG) Confirmed Hypoglycaemic Episodes
Description
Treatment emergent hypoglycaemic episode is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.
Severe or BG confirmed hypoglycaemic episodes were defined as episodes that were severe according to the American Diabetes Association (ADA) classification or BG confirmed by a plasma glucose value < 3.1 mmol/L (56 mg/dL) with or without symptoms consistent with hypoglycaemia.
Severe hypoglycaemia according to the ADA definition: an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. Plasma glucose concentrations may not be available during an event, but neurological recovery following the return of plasma glucose to normal is considered sufficient evidence that the event was induced by a low plasma glucose concentration.
Time Frame
During 26 weeks of treatment
Title
Daily Insulin Dose
Description
Actual daily total insulin dose after 26 weeks.
Time Frame
After 26 weeks
Title
Responder (Yes/no): HbA1c Less Than 7.0%
Description
Number of subjects with HbA1c less than 7.0% after 26 weeks.
Time Frame
After 26 weeks
Title
Responder (Yes/no): HbA1c Less Than 7.0% and Without Weight Gain
Description
Number of subjects with HbA1c less than 7.0% and without weight gain after 26 weeks.
Time Frame
After 26 weeks
Title
Responder (Yes/no): HbA1c Less Than 7.0% Without Treatment Emergent Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemic Episodes During the Last 12 Weeks of Treatment
Description
Number of subjects with HbA1c less than 7.0% after 26 weeks, who did not experience treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes during the last 12 weeks of treatment.
Treatment emergent hypoglycaemic episode is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.
Severe or BG confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification or BG confirmed by a plasma glucose value < 3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.
Time Frame
After 26 weeks
Title
Responder (Yes/no): HbA1c Less Than 7.0% and Without Weight Gain and Without Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During the Last 12 Weeks of Treatment
Description
Number of subjects with HbA1c less than 7.0% and no weight gain after 26 weeks, who did not experience treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes during the last 12 weeks of treatment.
Treatment emergent hypoglycaemic episode is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.
Severe or BG confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification or BG confirmed by a plasma glucose value < 3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.
Time Frame
After 26 weeks
Title
Responder (Yes/no): HbA1c Less Than or Equal to 6.5%
Description
Number of subjects with HbA1c less than or equal to 6.5% after 26 weeks.
Time Frame
After 26 weeks
Title
Responder (Yes/no): HbA1c Less Than or Equal to 6.5% and Without Weight Gain
Description
Number of subjects with HbA1c less than or equal to 6.5% and without weight gain
Time Frame
After 26 weeks
Title
Responder (Yes/no): HbA1c Less Than or Equal to 6.5% Without Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During the Last 12 Weeks of Treatment
Description
Number of subjects with HbA1c less than or equal to 6.5% after 26 weeks, who did not experience treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes during the last 12 weeks of treatment.
Treatment emergent hypoglycaemic episode is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.
Severe or BG confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification or BG confirmed by a plasma glucose value < 3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.
Time Frame
After 26 weeks
Title
Responder (Yes/no): HbA1c Less Than or Equal to 6.5% and Without Weight Gain and Without Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During the Last 12 Weeks of Treatment
Description
Number of subjects with HbA1c less than or equal to 6.5% and no weight gain after 26 weeks, who did not experience treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes during the last 12 weeks of treatment.
Treatment emergent hypoglycaemic episode is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.
Severe or BG confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification or BG confirmed by a plasma glucose value < 3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.
Time Frame
After 26 weeks
Title
Change in Waist Circumference
Description
Change from baseline (week 0) in waist circumference after 26 weeks of treatment.
Time Frame
week 0, week 26
Title
Change in Blood Pressure (Systolic and Diastolic)
Description
Change from baseline in blood pressure (systolic and diastolic) after 26 weeks of treatment.
Time Frame
week 0, week 26
Title
Self-measured Blood Glucose (SMBG) 9-point Profile (Individual Points in the Profile)
Description
Subjects were instructed to measure their plasma glucose at following timepoints: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner, at bedtime, at 4:00 a.m. and before breakfast the following day.
Time Frame
After 26 weeks
Title
Change in SMBG 9-point Profile: Mean of the 9-point Profile
Description
Subjects were instructed to measure their plasma glucose at following timepoints: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner, at bedtime, at 4:00 a.m. and before breakfast the following day. Mean of the 9-point profile was defined as the area under the profile (calculated using the trapezoidal method) divided by the measurement time.
Time Frame
Week 0, week 26
Title
Change in SMBG 9-point Profile: Mean of Postprandial Plasma Glucose Increments (From Before Meal to 90 Minutes After Breakfast, Lunch and Dinner)
Description
Subjects were instructed to measure their plasma glucose at following timepoints: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner, at bedtime, at 4:00 a.m. and before breakfast the following day. The mean increment over all meals was derived as the mean of all available meal increments.
Time Frame
Week 0, week 26
Title
Fasting Lipid Profile
Description
Lipid profile includes total cholesterol, low density lipoprotein cholesterol (LDL cholesterol), high density lipoprotein cholesterol (HDL cholesterol), very low density lipoprotein cholesterol (VLDL cholesterol), triglycerides and free fatty acids. Lipid profile parameters are represented as ratio to baseline values.
Time Frame
Week 0, week 26
Title
Number of Treatment Emergent Adverse Events (TEAE)
Description
Treatment emergent adverse event is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. If the event had onset date before the first day of exposure on randomised treatment and increased in severity during the treatment period and until 7 days after the last drug date, then this event was considered as a TEAE.
Time Frame
During 26 weeks of treatment
Title
Number of Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes
Description
Treatment emergent hypoglycaemic episode is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.
Severe or BG confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe according to the American Diabetes Association (ADA) classification or BG confirmed by a plasma glucose value < 3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.
Severe hypoglycaemia according to the ADA definition: an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. Plasma glucose concentrations may not be available during an event, but neurological recovery following the return of plasma glucose to normal is considered sufficient evidence that the event was induced by a low plasma glucose concentration.
Time Frame
During 26 weeks of treatment
Title
Number of Treatment Emergent Hypoglycaemic Episodes According to American Diabetes Association (ADA) Definition
Description
Results represent total number of treatment emergent hypoglycaemic episodes that fall under ADA's definition of hypoglycaemia. ADA's definition of hypoglycaemia includes following categories:
Severe hypoglycaemia
Documented symptomatic hypoglycaemia
Asymptomatic hypoglycaemia
Probable symptomatic hypoglycaemia
Pseudo-hypoglycaemia. Treatment emergent hypoglycaemic episode is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product.
Time Frame
During 26 weeks of treatment
Title
Number of Treatment Emergent Nocturnal Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes
Description
Treatment emergent hypoglycaemic episode is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Nocturnal period: The period between 00:01 and 05:59 a.m. (both inclusive).
Severe or BG confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe according to the American Diabetes Association (ADA) classification or BG confirmed by a plasma glucose value < 3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.
Severe hypoglycaemia according to the ADA definition: an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. Plasma glucose concentrations may not be available during an event, but neurological recovery following the return of plasma glucose to normal is considered sufficient evidence that the event was induced by a low plasma glucose concentration.
Time Frame
During 26 weeks of treatment
Title
Change in Clinical Evaluation: Fundoscopy or Fundus Photography
Description
The result of the fundus photography/dilated fundoscopy was interpreted by the investigator into following categories: Normal; Abnormal (Abn), Not Clinically significant (NCS); Abnormal, Clinically significant (CS). Reported results are number of subjects with 'normal'; 'Abn, NCS' and 'Abn, CS' fundoscopy/fundus photography results at screening (week -2 to week 0) and week 26.
Time Frame
Screening (week -2 to week 0), week 26
Title
Change in Clinical Evaluation: Electrocardiogram (ECG)
Description
The result of the ECG was interpreted by the investigator into following categories: Normal; Abnormal (Abn), Not Clinically significant (NCS); Abnormal, Clinically significant (CS). Reported results are number of subjects with 'normal'; 'Abn, NCS' and 'Abn, CS' ECG results at screening (week -2 to week 0) and week 26.
Time Frame
Screening (week -2 to week 0), week 26
Title
Change in Pulse
Description
Change in pulse after 26 weeks of treatment.
Time Frame
Week 0, week 26
Title
Change From Baseline in Patient Reported Outcomes (PROs) of Treatment: Diabetes Therapy-Related Quality of Life (DTR-QOL)Questionnaire
Description
For the DTR-QOL questionnaire, change from baseline in the 'Total score' and the following four 'Domain scores' were analysed:
Burden on social activities and daily activities
Anxiety and dissatisfaction with treatment
Hypoglycaemia
Satisfaction with treatment. The scoring range of 'Total score' was converted to 0-100 (best case response = 100; worst case response = 0).
The scoring range for each of four domains was converted to 0-100 (best case response = 100; worst case response = 0).
Time Frame
week 0, week 26
Title
Change From Baseline in Patient Reported Outcomes (PROs) of Treatment: EuroQol-5D (EQ-5D-5L) Questionnaire
Description
Overall health state was rated by patients using the EQ-5D-5L visual analogue scale (VAS) and the EQ-5D-5L index score. The EQ-5D-5L VAS is a vertical scale where patients can rank their health from 0 (worst health imaginable) to 100 (best health imaginable).
The EQ-5D-5L index score was calculated based on the 5 dimensions, i.e., mobility, self-care, usual activities (e.g., work, study), pain/discomfort and anxiety/depression with five response levels for each dimension, i.e., no problems, slight problems, moderate problems, severe problems and extreme problems. The scores from 5 dimensions are then converted to the EQ-5D-5L index score scale: 0 - 1 (full health/best-case response = 1; death/worst-case response = 0).
Time Frame
week 0, week 26
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female Japanese subjects, age at least 20 years at the time of signing informed consent
T2DM (type 2 diabetes mellitus) subjects (diagnosed clinically) for at least 6 months prior to screening
HbA1c (glycosylated haemoglobin) 7.5-11.0 per cent [58 mmol/mol-97 mmol/mol] (both inclusive) by central laboratory analysis
Subjects on stable daily insulin doses for at least 60 days prior to screening administered once or twice daily, either as basal insulin (e.g. IDeg, insulin glargine, insulin detemir, NPH insulin) or pre-mix/combination insulin (e.g. biphasic insulin aspart, insulin degludec/insulin aspart). Total daily insulin dose in the previous 60 days should be within 20-50 units, both inclusive, and on the day of screening, but fluctuations of plus/minus 20 per cent within the 60 days prior to screening are acceptable. The specified insulin treatment should be administered in combination with a stable daily dose of metformin within current approved Japanese label for at least 60 days prior to screening - additionally, the anti-diabetic treatment can be with or without a stable daily dose of one of the following other OADs (oral anti-diabetic drug): SU (sulfonylureas), glinides, alpha-glucosidase inhibitor, SGLT2i (sodium glucose co-transporter 2 inhibitor) or TZD (thiazolidinedione) within current approved Japanese label for at least 60 days prior to screening
Body Mass Index (BMI) equal or above 23 kg/m^2
Exclusion Criteria:
Receipt of any investigational medicinal product (IMP) within 30 days before screening
Use of any anti-diabetic drug in a period of 60 days before screening (except premix/ combination or basal insulin, metformin, SU, glinides, α-GI, SGLT2i, or TZD) or anticipated change in concomitant medication, which in the investigators opinion could interfere with glucose metabolism (e.g. systemic corticosteroids or bolus insulin)
Treatment with glucagon-like peptide-1 (GLP-1) receptor agonist during the last 60 days prior to screening and furthermore, the discontinuation of GLP-1 receptor agonist at any point in time must not have been due to safety concerns, tolerability issues or lack of efficacy, as judged by the investigator
Treatment with dipetidyl peptidase-4 (DPP-4) inhibitors during the last 60 days prior to screening - Impaired liver function, defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) equal or above 2.5 times upper limit of normal
Renal impairment estimated Glomerular Filtration Rate (eGFR) below 60 mL/min/1.73m^2 as per Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
Screening calcitonin equal or above 50 ng/L
History of pancreatitis (acute or chronic)
Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN 2)
Subjects presently classified as being in New York Heart Association (NYHA) Class IV
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Global Clinical Registry (GCR, 1452)
Organizational Affiliation
Novo Nordisk A/S
Official's Role
Study Director
Facility Information:
Facility Name
Novo Nordisk Investigational Site
City
Asahikawa-shi, Hokkaido
ZIP/Postal Code
078-8211
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Chigasaki-shi, Kanagawa
ZIP/Postal Code
253-0044
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Chitose, Hokkaido
ZIP/Postal Code
066-0032
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Chiyoda-ku, Tokyo
ZIP/Postal Code
101-0024
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Fujisawa-shi, Kanagawa
ZIP/Postal Code
251-0041
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Fukui-shi, Fukui
ZIP/Postal Code
918-8503
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Fukuoka-shi, Fukuoka
ZIP/Postal Code
810-0001
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Fukuoka-shi, Fukuoka
ZIP/Postal Code
819-0006
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Fukuoka
ZIP/Postal Code
830 8522
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Fukushima
ZIP/Postal Code
963-8851
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Hokkaido
ZIP/Postal Code
060-0062
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Ibaraki
ZIP/Postal Code
311-0113
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Kanagawa
ZIP/Postal Code
235-0045
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Kashiwara-shi, Osaka
ZIP/Postal Code
582-0005
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Kawagoe-shi, Saitama
ZIP/Postal Code
350-0851
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Kawaguchi-shi, Saitama
ZIP/Postal Code
332-0012
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Kumamoto-shi, Kumamoto
ZIP/Postal Code
862-0965
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Kumamoto
ZIP/Postal Code
862-0976
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Mitaka-shi, Tokyo
ZIP/Postal Code
181-0013
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Miyazaki
ZIP/Postal Code
880-0034
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Nagano
ZIP/Postal Code
390-8621
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Nakagami, Okinawa
ZIP/Postal Code
901-2393
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Neyagawa-shi, Osaka
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Niigata-shi, Niigata
ZIP/Postal Code
950 1104
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Okawa-shi, Fukuoka
ZIP/Postal Code
831-0016
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Osaka-shi, Osaka
ZIP/Postal Code
536-0001
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Osaka
ZIP/Postal Code
569-1045
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Ota-ku, Tokyo
ZIP/Postal Code
1430015
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Saitama-shi, Saitama
ZIP/Postal Code
336-0967
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Sendai-shi, Miyagi
ZIP/Postal Code
980-0021
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Shimotsuke-shi, Tochigi
ZIP/Postal Code
329-0433
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Tochigi
ZIP/Postal Code
323-0022
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Tokyo
ZIP/Postal Code
103-0027
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Tokyo
ZIP/Postal Code
103-0028
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Tokyo
ZIP/Postal Code
113-8431
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Tomigusuku-shi, Okinawa
ZIP/Postal Code
901-0243
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Tomigusuku-shi, Okinawa
ZIP/Postal Code
901-0244
Country
Japan
Facility Name
Novo Nordisk Investigational Site
City
Yamaguchi-shi, Yamaguchi
ZIP/Postal Code
754-0002
Country
Japan
12. IPD Sharing Statement
Citations:
PubMed Identifier
31423685
Citation
Watada H, Kaneko S, Komatsu M, Agner BR, Nishida T, Ranthe M, Nakamura J. Superior HbA1c control with the fixed-ratio combination of insulin degludec and liraglutide (IDegLira) compared with a maximum dose of 50 units of insulin degludec in Japanese individuals with type 2 diabetes in a phase 3, double-blind, randomized trial. Diabetes Obes Metab. 2019 Dec;21(12):2694-2703. doi: 10.1111/dom.13859. Epub 2019 Sep 17.
Results Reference
result
PubMed Identifier
33595901
Citation
Komatsu M, Watada H, Kaneko S, Ross Agner BF, Nishida T, Kaku K. Efficacy and safety of the fixed-ratio combination of insulin degludec and liraglutide by baseline glycated hemoglobin, body mass index and age in Japanese individuals with type 2 diabetes: A subgroup analysis of two phase III trials. J Diabetes Investig. 2021 Sep;12(9):1610-1618. doi: 10.1111/jdi.13525. Epub 2021 Mar 24.
Results Reference
result
PubMed Identifier
31760599
Citation
Watada H, Ross Agner BF, Doshi A, Bardtrum L, Ranthe MF, Billings LK. IDegLira Improves Glycemic Control in Japanese Patients with Uncontrolled Type 2 Diabetes on Premixed Insulin Therapy. Diabetes Ther. 2020 Jan;11(1):331-339. doi: 10.1007/s13300-019-00730-y. Epub 2019 Nov 23.
Results Reference
derived
Learn more about this trial
A Double-blinded Trial Comparing the Efficacy and Safety of Insulin Degludec/Liraglutide and Insulin Degludec Both in Combination With Metformin in Japanese Subjects With Type 2 Diabetes Mellitus Inadequately Controlled With Basal or Pre-mix/Combination Insulin Therapy and Oral Anti-diabetic Drugs
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