DiabetesPhase 3DUAL™ II JapanNCT02911948
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
A Phase 3 study testing Insulin degludec/liraglutide and Insulin degludec in people with Diabetes and Diabetes Mellitus, Type 2, run by Novo Nordisk A/S at 38 sites in Japan.
Trial 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… Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Diabetes, Diabetes Mellitus, Type 2
- What is being tested?
- Insulin degludec/liraglutide and Insulin degludec
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 210 participants
- Where
- 38 sitesJapan
- Study dates
- 21 Sep 2016to 22 Nov 2017
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
38 sites in 1 country.
38 sites in 1 country
Japan38 sites
Novo Nordisk Investigational Site
Asahikawa-shi, Hokkaido, 078-8211
Novo Nordisk Investigational Site
Chigasaki-shi, Kanagawa, 253-0044
Novo Nordisk Investigational Site
Chitose, Hokkaido, 066-0032
Novo Nordisk Investigational Site
Chiyoda-ku, Tokyo, 101-0024
Novo Nordisk Investigational Site
Fujisawa-shi, Kanagawa, 251-0041
Novo Nordisk Investigational Site
Fukui-shi, Fukui, 918-8503
Novo Nordisk Investigational Site
Fukuoka, 830 8522
Novo Nordisk Investigational Site
Fukuoka-shi, Fukuoka, 810-0001
Novo Nordisk Investigational Site
Fukuoka-shi, Fukuoka, 819-0006
Novo Nordisk Investigational Site
Fukushima, 963-8851
Novo Nordisk Investigational Site
Hokkaido, 060-0062
Novo Nordisk Investigational Site
Ibaraki, 311-0113
Novo Nordisk Investigational Site
Kanagawa, 235-0045
Novo Nordisk Investigational Site
Kashiwara-shi, Osaka, 582-0005
Novo Nordisk Investigational Site
Kawagoe-shi, Saitama, 350-0851
Novo Nordisk Investigational Site
Kawaguchi-shi, Saitama, 332-0012
Novo Nordisk Investigational Site
Kumamoto, 862-0976
Novo Nordisk Investigational Site
Kumamoto-shi, Kumamoto, 862-0965
Novo Nordisk Investigational Site
Mitaka-shi, Tokyo, 181-0013
Novo Nordisk Investigational Site
Miyazaki, 880-0034
Novo Nordisk Investigational Site
Nagano, 390-8621
Novo Nordisk Investigational Site
Nakagami, Okinawa, 901-2393
Novo Nordisk Investigational Site
Neyagawa-shi, Osaka
Novo Nordisk Investigational Site
Niigata-shi, Niigata, 950 1104
Novo Nordisk Investigational Site
Okawa-shi, Fukuoka, 831-0016
Novo Nordisk Investigational Site
Osaka, 569-1045
Novo Nordisk Investigational Site
Osaka-shi, Osaka, 536-0001
Novo Nordisk Investigational Site
Ota-ku, Tokyo, 1430015
Novo Nordisk Investigational Site
Saitama-shi, Saitama, 336-0967
Novo Nordisk Investigational Site
Sendai-shi, Miyagi, 980-0021
Novo Nordisk Investigational Site
Shimotsuke-shi, Tochigi, 329-0433
Novo Nordisk Investigational Site
Tochigi, 323-0022
Novo Nordisk Investigational Site
Tokyo, 103-0027
Novo Nordisk Investigational Site
Tokyo, 103-0028
Novo Nordisk Investigational Site
Tokyo, 113-8431
Novo Nordisk Investigational Site
Tomigusuku-shi, Okinawa, 901-0243
Novo Nordisk Investigational Site
Tomigusuku-shi, Okinawa, 901-0244
Novo Nordisk Investigational Site
Yamaguchi-shi, Yamaguchi, 754-0002
About this study
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.
- Conditions
- Diabetes, Diabetes Mellitus, Type 2
- Being tested
- Insulin degludec/liraglutide, Insulin degludec
- Medical subject headings
- Diabetes Mellitus, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Insulin degludec/liraglutideDrug
Injected s.c. / subcutaneously (under the skin) once daily
Insulin degludecDrug
Injected s.c. / subcutaneously (under the skin) once daily
| Study group | Role | What they receive |
|---|---|---|
| Insulin degludec/liraglutide | Experimental | Not described Receives: Drug: Insulin degludec/liraglutide |
| Insulin degludec | Active comparator | Not described Receives: Drug: Insulin degludec |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Glycosylated Haemoglobin (HbA1c)
Change from baseline (week 0) in HbA1c after 26 weeks of treatment.
Measured: week 0, week 26
Secondary outcomes (27)
Change in Body Weight
Change from baseline (week 0) in body weight after 26 weeks of treatment.
Measured: week 0, week 26
Change in Fasting Plasma Glucose (FPG)
Change from baseline (week 0) in FPG after 26 weeks of treatment.
Measured: week 0, week 26
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.
Measured: During 26 weeks of treatment
Daily Insulin Dose
Actual daily total insulin dose after 26 weeks.
Measured: After 26 weeks
Responder (Yes/no): HbA1c Less Than 7.0%
Number of subjects with HbA1c less than 7.0% after 26 weeks.
Measured: 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.
Measured: 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.
Measured: After 26 weeks
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.
Measured: After 26 weeks
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.
Measured: 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
Measured: After 26 weeks
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.
Measured: After 26 weeks
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.
Measured: After 26 weeks
Change in Waist Circumference
Change from baseline (week 0) in waist circumference after 26 weeks of treatment.
Measured: week 0, week 26
Change in Blood Pressure (Systolic and Diastolic)
Change from baseline in blood pressure (systolic and diastolic) after 26 weeks of treatment.
Measured: week 0, week 26
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.
Measured: After 26 weeks
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.
Measured: Week 0, week 26
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.
Measured: Week 0, week 26
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.
Measured: Week 0, week 26
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.
Measured: During 26 weeks of treatment
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.
Measured: During 26 weeks of treatment
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.
Measured: During 26 weeks of treatment
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.
Measured: During 26 weeks of treatment
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.
Measured: Screening (week -2 to week 0), 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.
Measured: Screening (week -2 to week 0), week 26
Change in Pulse
Change in pulse after 26 weeks of treatment.
Measured: Week 0, week 26
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).
Measured: week 0, week 26
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).
Measured: week 0, week 26
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2016 (estimated)
- Study start21 Sep 2016
- Primary completion17 Nov 2017
- Study completion22 Nov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for DiabetesStudies of the same condition, open and under way.
- More trials run by Novo Nordisk A/SThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 210 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novo Nordisk A/S
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Global Clinical Registry (GCR, 1452), Study director, Novo Nordisk A/S
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02911948
- Sponsor's protocol ID
- NN9068-4184
- Other IDs
- U1111-1178-3453, JapicCTI-163385
- Acronym
- DUAL™ II Japan
- Status last verified
- Mar 2021
- First submitted
- 20 Sep 2016
- Last updated
- 9 Apr 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 31423685Komatsu 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.
PubMed 33595901Watada 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.
PubMed 31760599
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02911948
- Acronym / sponsor ID
- DUAL™ II Japan / NN9068-4184
- Conditions
- Diabetes, Diabetes Mellitus, Type 2
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 210 participants (actual)
- Lead sponsor
- Novo Nordisk A/SIndustry (pharma, biotech, devices)
- Study start
- 21 Sep 2016 (actual)
- Primary completion
- 17 Nov 2017 (actual)
- Study completion
- 22 Nov 2017 (actual)
- First posted
- 23 Sep 2016 (estimated)
- Results
- Posted 11 Mar 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Insulin degludec/liraglutide | Experimental | Drug: Insulin degludec/liraglutide |
| Insulin degludec | Active comparator | Drug: Insulin degludec |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (9 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Insulin degludec/liraglutideInjected s.c. / subcutaneously (under the skin) once daily | Drug | Insulin degludec/liraglutide |
| Insulin degludecInjected s.c. / subcutaneously (under the skin) once daily | Drug | Insulin degludec |
Primary outcome
Change in Glycosylated Haemoglobin (HbA1c)
Time frame: week 0, week 26
Change from baseline (week 0) in HbA1c after 26 weeks of treatment.
27 secondary outcomes
Change in Body Weight
Time frame: week 0, week 26
Change in Fasting Plasma Glucose (FPG)
Time frame: week 0, week 26
Number of Treatment Emergent Severe or Blood Glucose (BG) Confirmed Hypoglycaemic Episodes
Time frame: During 26 weeks of treatment
Daily Insulin Dose
Time frame: After 26 weeks
Responder (Yes/no): HbA1c Less Than 7.0%
Time frame: After 26 weeks
Responder (Yes/no): HbA1c Less Than 7.0% and Without Weight Gain
Time frame: 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
Time frame: After 26 weeks
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
Time frame: After 26 weeks
Responder (Yes/no): HbA1c Less Than or Equal to 6.5%
Time frame: After 26 weeks
Responder (Yes/no): HbA1c Less Than or Equal to 6.5% and Without Weight Gain
Time frame: After 26 weeks
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
Time frame: After 26 weeks
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
Time frame: After 26 weeks
Change in Waist Circumference
Time frame: week 0, week 26
Change in Blood Pressure (Systolic and Diastolic)
Time frame: week 0, week 26
Self-measured Blood Glucose (SMBG) 9-point Profile (Individual Points in the Profile)
Time frame: After 26 weeks
Change in SMBG 9-point Profile: Mean of the 9-point Profile
Time frame: Week 0, week 26
Change in SMBG 9-point Profile: Mean of Postprandial Plasma Glucose Increments (From Before Meal to 90 Minutes After Breakfast, Lunch and Dinner)
Time frame: Week 0, week 26
Fasting Lipid Profile
Time frame: Week 0, week 26
Number of Treatment Emergent Adverse Events (TEAE)
Time frame: During 26 weeks of treatment
Number of Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes
Time frame: During 26 weeks of treatment
Number of Treatment Emergent Hypoglycaemic Episodes According to American Diabetes Association (ADA) Definition
Time frame: During 26 weeks of treatment
Number of Treatment Emergent Nocturnal Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes
Time frame: During 26 weeks of treatment
Change in Clinical Evaluation: Fundoscopy or Fundus Photography
Time frame: Screening (week -2 to week 0), week 26
Change in Clinical Evaluation: Electrocardiogram (ECG)
Time frame: Screening (week -2 to week 0), week 26
Change in Pulse
Time frame: Week 0, week 26
Change From Baseline in Patient Reported Outcomes (PROs) of Treatment: Diabetes Therapy-Related Quality of Life (DTR-QOL)Questionnaire
Time frame: week 0, week 26
Change From Baseline in Patient Reported Outcomes (PROs) of Treatment: EuroQol-5D (EQ-5D-5L) Questionnaire
Time frame: week 0, week 26
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 31423685Watada 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 publication: PubMed 33595901Komatsu 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.
- Derived from this study: PubMed 31760599Watada 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.
Related trials for Diabetes
Not yet recruitingPhase 3
Efficacy and Safety of Once-Weekly SHR-3167 Compared With Once-Daily Insulin Glargine in Adults With Insulin-Naive Type 2 Diabetes
Type 2 Diabetes
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Effects of Lean Pork Loin Intake on Protein Homeostasis and Glucose Regulation in Prediabetic Adults
Hyperglycaemia (Non Diabetic), Prediabetes
Recruiting
PAW-Hydrogel for Chronic Wound Healing
Diabetic Foot Ulcer (DFU), Pressure Ulcer (PU)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Global Clinical Registry (GCR, 1452) study director
Novo Nordisk A/S
38 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Insulin degludec/liraglutide and Insulin degludec in people with Diabetes and Diabetes Mellitus, Type 2, run by Novo Nordisk A/S at 38 sites in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 38 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Mar 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Glycosylated Haemoglobin (HbA1c) (time frame: week 0, week 26). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02911948, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Apr 2021.