A Trial Comparing the Efficacy and Safety of Insulin Degludec/Liraglutide, Insulin Degludec and Liraglutide in Japanese Subjects With Type 2 Diabetes Mellitus. (DUAL™ I Japan)

A Trial Comparing the Efficacy and Safety of Insulin Degludec/Liraglutide, Insulin Degludec and Liraglutide in Japanese Subjects With Type 2 Diabetes Mellitus

This trial is conducted in Asia. The aim of this trial is to compare the efficacy and safety of insulin degludec/liraglutide, insulin degludec and liraglutide in Japanese subjects with type 2 diabetes mellitus.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2; Diabetes
• Intervention / Treatment: Drug: insulin degludec/liraglutide; Drug: insulin degludec; Drug: liraglutide

• Study Type: Interventional
• Enrollment (Actual): 819
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Adachi-ku, Tokyo, Japan, 123-0845
    • Novo Nordisk Investigational Site
  • Akita-shi, Akita, Japan, 010-8543
    • Novo Nordisk Investigational Site
  • Annaka-shi, Gunma, Japan, 379-0116
    • Novo Nordisk Investigational Site
  • Asahikawa-shi, Hokkaido, Japan, 070-0002
    • Novo Nordisk Investigational Site
  • Chiba-shi, Chiba, Japan, 260-0804
    • Novo Nordisk Investigational Site
  • Chitose, Hokkaido, Japan, 066-0032
    • Novo Nordisk Investigational Site
  • Chuo-ku,, Japan, 104 0061
    • Novo Nordisk Investigational Site
  • Chuo-ku, Tokyo, Japan, 103-0002
    • Novo Nordisk Investigational Site
  • Chuo-ku,Tokyo, Japan, 103-0025
    • Novo Nordisk Investigational Site
  • Edogawa-ku, Tokyo, Japan, 134-0084
    • Novo Nordisk Investigational Site
  • Fujisawa-shi, Kanagawa, Japan, 251-0041
    • Novo Nordisk Investigational Site
  • Fukuoka-shi, Fukuoka, Japan, 819-0168
    • Novo Nordisk Investigational Site
  • Fukushima, Japan, 963-8851
    • Novo Nordisk Investigational Site
  • Gunma, Japan, 373-0036
    • Novo Nordisk Investigational Site
  • Hachioji-shi, Tokyo, Japan, 192-0917
    • Novo Nordisk Investigational Site
  • Hokkaido, Japan, 060-0062
    • Novo Nordisk Investigational Site
  • Hokkaido, Japan, 078-8236
    • Novo Nordisk Investigational Site
  • Ibaraki, Japan, 311-0113
    • Novo Nordisk Investigational Site
  • Ichihara-shi, Chiba, Japan, 290-0003
    • Novo Nordisk Investigational Site
  • Iruma-shi, Saitama, Japan, 358-0011
    • Novo Nordisk Investigational Site
  • Itabashi-ku, Tokyo, Japan, 173-0004
    • Novo Nordisk Investigational Site
  • Itabashi-ku, Tokyo, Japan, 175-0093
    • Novo Nordisk Investigational Site
  • Izumisano-shi, Japan, 598 0048
    • Novo Nordisk Investigational Site
  • Izumisano-shi,Osaka, Japan, 598-8577
    • Novo Nordisk Investigational Site
  • Kagoshima-shi, Kagoshima, Japan, 890-0061
    • Novo Nordisk Investigational Site
  • Kamakura-shi, Japan, 247 0056
    • Novo Nordisk Investigational Site
  • Kanagawa, Japan, 235-0045
    • Novo Nordisk Investigational Site
  • Kanra-gun, Gunma, Japan, 370-2214
    • Novo Nordisk Investigational Site
  • Kashiwara-shi, Osaka, Japan, 582-0005
    • Novo Nordisk Investigational Site
  • Kawagoe-shi, Saitama, Japan, 350-0851
    • Novo Nordisk Investigational Site
  • Kawaguchi-shi, Saitama, Japan, 332-0012
    • Novo Nordisk Investigational Site
  • Kawasaki-shi,Kanagawa, Japan, 215-0026
    • Novo Nordisk Investigational Site
  • Kisarazu-shi, Chiba, Japan, 292-0038
    • Novo Nordisk Investigational Site
  • Kobe-shi, Hyogo, Japan
    • Novo Nordisk Investigational Site
  • Kuki-shi, Saitama, Japan, 346-8530
    • Novo Nordisk Investigational Site
  • Kumamoto, Japan, 862-0976
    • Novo Nordisk Investigational Site
  • Kumamoto-shi, Kumamoto, Japan, 860-0811
    • Novo Nordisk Investigational Site
  • Kumamoto-shi, Kumamoto, Japan, 861-8039
    • Novo Nordisk Investigational Site
  • Kushiro-shi, Hokkaido, Japan, 085-0032
    • Novo Nordisk Investigational Site
  • Kyoto-shi, Kyoto, Japan, 606-8507
    • Novo Nordisk Investigational Site
  • Minato-ku, Tokyo, Japan, 108-0075
    • Novo Nordisk Investigational Site
  • Mito-shi, Ibaraki, Japan, 310-0826
    • Novo Nordisk Investigational Site
  • Mito-shi, Ibaraki, Japan, 311-4153
    • Novo Nordisk Investigational Site
  • Miura-shi, Kanagawa, Japan, 238-0101
    • Novo Nordisk Investigational Site
  • Miyazaki, Japan, 880-0034
    • Novo Nordisk Investigational Site
  • Nagoya-shi, Aichi, Japan, 455-8530
    • Novo Nordisk Investigational Site
  • Nagoya-shi, Aichi, Japan, 456-0058
    • Novo Nordisk Investigational Site
  • Nishinomiya-shi, Hygo, Japan, 662 0971
    • Novo Nordisk Investigational Site
  • Obihiro-shi, Hokkaido, Japan, 080 0016
    • Novo Nordisk Investigational Site
  • Obihiro-shi, Hokkaido, Japan, 080 0848
    • Novo Nordisk Investigational Site
  • Oita-shi, Japan, 870 0039
    • Novo Nordisk Investigational Site
  • Okawa-shi, Fukuoka, Japan, 831-0016
    • Novo Nordisk Investigational Site
  • Onga-gun, Fukuoka, Japan, 811-4342
    • Novo Nordisk Investigational Site
  • Osaka, Japan, 569-1045
    • Novo Nordisk Investigational Site
  • Osaka-shi, Osaka, Japan, 530-0013
    • Novo Nordisk Investigational Site
  • Osaka-shi, Osaka, Japan, 533-0024
    • Novo Nordisk Investigational Site
  • Osaka-shi, Osaka, Japan, 536-0001
    • Novo Nordisk Investigational Site
  • Ota-ku, Tokyo, Japan, 1430015
    • Novo Nordisk Investigational Site
  • Saijo-shi, Ehime, Japan, 793-0027
    • Novo Nordisk Investigational Site
  • Sapporo-shi, Hokkaido, Japan, 060-0001
    • Novo Nordisk Investigational Site
  • Sapporo-shi, Hokkaido, Japan, 004-0004
    • Novo Nordisk Investigational Site
  • Sendai-shi, Miyagi, Japan, 980-0011
    • Novo Nordisk Investigational Site
  • Sendai-shi, Miyagi, Japan, 980-0021
    • Novo Nordisk Investigational Site
  • Shimotsuke-shi, Tochigi, Japan, 329-0433
    • Novo Nordisk Investigational Site
  • Shizuoka-shi, Shizuoka, Japan, 424-0853
    • Novo Nordisk Investigational Site
  • Tochigi, Japan, 323-0022
    • Novo Nordisk Investigational Site
  • Tokyo, Japan, 103-0027
    • Novo Nordisk Investigational Site
  • Tokyo, Japan, 103-0028
    • Novo Nordisk Investigational Site
  • Tokyo, Japan, 104-0031
    • Novo Nordisk Investigational Site
  • Tokyo, Japan, 169-0073
    • Novo Nordisk Investigational Site
  • Toshima-ku, Tokyo, Japan, 171-0021
    • Novo Nordisk Investigational Site
  • Toyonaka-shi, Osaka, Japan, 560-0082
    • Novo Nordisk Investigational Site
  • Ube-shi, Yamaguchi, Japan, 755-0046
    • Novo Nordisk Investigational Site
  • Urasoe-shi,, Japan, 901 2104
    • Novo Nordisk Investigational Site
  • Yamaguchi-shi, Yamaguchi, Japan, 754-0002
    • Novo Nordisk Investigational Site
  • Yamato-shi, Kanagawa, Japan, 242-0004
    • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female Japanese subjects, age at least 20 years at the time of signing informed consent
• Type 2 diabetes subjects (diagnosed clinically) at least 6 months prior to screening
• HbA1c (glycosylated haemoglobin) 7.0-11.0 % (both inclusive) by central laboratory analysis, with the aim of a median of 8.3%. When approximately 50% of the randomised subjects have a HbA1c above 8.3%, the remaining subjects randomised must have a HbA1c below or equal to 8.3%; or when approximately 50% of the randomised subjects have a HbA1c below or equal to 8.3%, the remaining subjects randomised must have a HbA1c above 8.3%
• Body-mass index (BMI) above or equal to 20 kg/m^2
• Subjects on stable therapy with one OAD (defined as unchanged medication and unchanged dose) for at least 60 days (metformin, a-GI, TZD, SU, SGLT2i or glinide) prior to screening according to approved Japanese labelling

Exclusion Criteria:

• Previous treatment with insulin (except for short-term treatment in connection with intercurrent illness including gestational diabetes)
• Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria in a period of 60 days before screening
• Anticipated initiation or change in concomitant medications in excess of 14 days known to affect weight or glucose metabolism
• Impaired liver function, defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) equal to or above 2.5 times upper limit of normal
• Renal impairment estimated Glomerular Filtration Rate (eGFR) below 60mL/min/1.73m^2 as per Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
• Screening calcitonin equal to 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Insulin degludec/liraglutide OD	Drug: insulin degludec/liraglutide; Injected s.c. / subcutaneously (under the skin) once daily (OD) , in combination with pre-trial OAD (oral antidiabetic drug)kept in unchanged dose.
Active Comparator: Insulin degludec OD	Drug: insulin degludec; Injected s.c. / subcutaneously (under the skin) once daily (OD) , in combination with pre-trial OAD (oral antidiabetic drug)kept in unchanged dose.
Active Comparator: Liraglutide OD	Drug: liraglutide; Injected s.c. / subcutaneously (under the skin) once daily (OD) , in combination with pre-trial OAD (oral antidiabetic drug)kept in unchanged dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in HbA1c (Glycosylated Haemoglobin) Tested for Non-inferiority of IDegLira vs IDeg and Superiority of IDegLira vs Lira	Change from baseline (week 0) in HbA1c after 52 weeks of treatment was measured. Statistical analyses were performed to test the hypotheses: non-inferiority of IDegLira vs. IDeg and superiority of IDegLira vs. Liraglutide (Lira).	Week 0, Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Body Weight (kg)	Change from baseline (week 0) in body weight after 52 weeks of treatment.	Week 0, Week 52
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.	Weeks 0-52
Change From Baseline in HbA1c (Glycosylated Haemoglobin) Tested for Superiority of IDegLira vs IDeg	Change from baseline (week 0) in HbA1c after 52 weeks of treatment was measured. Statistical analysis was performed to test the hypothesis: superiority of IDegLira vs. IDeg.	Week 0, Week 52
Change From Baseline in Fasting Plasma Glucose (FPG)	Change from baseline (week 0) in FPG after 52 weeks	Week 0, Week 52
Insulin Dose	Actual daily total insulin dose after 52 weeks of treatment.	After 52 weeks of treatment
Responder (Yes/no): HbA1c Less Than 7.0%	Number of subjects with HbA1c less than 7.0% after 52 weeks of treatment.	After 52 weeks of treatment
Responder (Yes/no): HbA1c Less Than 7.0% and Change in Body Weight From Baseline Below or Equal to Zero	Number of subjects with HbA1c less than 7.0% and without weight gain after 52 weeks of treatment.	After 52 weeks of treatment
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 52 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.	After 52 weeks of treatment
Responder (Yes/no): HbA1c Less Than 7.0% and Change in Body Weight From Baseline Below or Equal to Zero 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 without weight gain, 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.	After 52 weeks of treatment
Responder (Yes/no): HbA1c Less Than 6.5%	Number of subjects with HbA1c less than 6.5% after 52 weeks of treatment.	After 52 weeks of treatment
Responder (Yes/no): HbA1c Less Than 6.5% and Change in Body Weight From Baseline Below or Equal to Zero	Number of subjects with HbA1c less than 6.5% and without weight gain after 52 weeks of treatment.	After 52 weeks of treatment
Responder (Yes/no): HbA1c Less Than 6.5% 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 6.5% after 52 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.	After 52 weeks of treatment
Responder (Yes/no): HbA1c Less Than 6.5% and Change in Body Weight From Baseline Below or Equal to Zero 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 6.5% with no weight gain, 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.	After 52 weeks of treatment
Change in Waist Circumference	Change from baseline (week 0) in waist circumference after 52 weeks of treatment.	Week 0, Week 52
Change in Blood Pressure (Systolic and Diastolic)	Change from baseline in blood pressure (systolic and diastolic) after 52 weeks of treatment.	Week 0, Week 52
Self-Measured Blood Glucose (SMBG) 9-point Profile: 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.	After 52 weeks of the treatment
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.	Week 0, week 52
Change in SMBG 9-point Profile - Mean of Postprandial Increments (From Before Meal to 90 Min After for 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.	Week 0, week 52
Total Cholesterol as a Ratio to Baseline at 52 Weeks	Total cholesterol after 52 weeks of treatment was represented as ratio to baseline (week 0) values.	After 52 weeks of treatment
Low Density Lipoprotein (LDL) Cholesterol as a Ratio to Baseline at 52 Weeks	Low density lipoprotein (LDL) cholesterol after 52 weeks of treatment was represented as ratio to baseline (week 0) values.	After 52 weeks of treatment
High Density Lipoprotein (HDL) Cholesterol as a Ratio to Baseline at 52 Weeks	High density lipoprotein (HDL) cholesterol after 52 weeks of treatment was represented as ratio to baseline (week 0) values.	After 52 weeks of treatment
Very Low Density Lipoprotein (VLDL) Cholesterol as a Ratio to Baseline at 52 Weeks	Very low density lipoprotein (VLDL) cholesterol after 52 weeks of treatment was represented as ratio to baseline (week 0) values.	After 52 weeks of treatment
Triglycerides as a Ratio to Baseline at 52 Weeks	Triglycerides after 52 weeks of treatment was represented as ratio to baseline (week 0) values.	After 52 weeks of treatment
Free Fatty Acids as a Ratio to Baseline at 52 Weeks	Free fatty acids after 52 weeks of treatment was represented as ratio to baseline (week 0) values.	After 52 weeks of treatment
Fasting C-peptide as a Ratio to Baseline at 52 Weeks	Fasting C-peptide after 52 weeks of treatment was represented as ratio to baseline (week 0) values.	After 52 weeks of treatment
Fasting Human Insulin as a Ratio to Baseline at 52 Weeks	Fasting human insulin after 52 weeks of treatment was represented as ratio to baseline (week 0) values.	After 52 weeks of treatment
Fasting Glucagon as a Ratio to Baseline at 52 Weeks	Fasting glucagon after 52 weeks of treatment was represented as ratio to baseline (week 0) values.	After 52 weeks of treatment
Proinsulin as a Ratio to Baseline at 52 Weeks	Proinsulin after 52 weeks of treatment was represented as ratio to baseline (week 0) values.	After 52 weeks of treatment
Number of Treatment Emergent Adverse Events (TEAEs)	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.	0-52 weeks
Number of Treatment Emergent Severe or Blood Glucose (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.	0-52 weeks
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.	0-52 weeks
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.	0-52 weeks
Anti-drug Antibodies: Anti-insulin Degludec Antibodies	Insulin degludec (IDeg)-specific antibodies were measured at week 52, as %B/T (percentage of bound & precipitated radioactive drug/total added drug to the sample). A sample is measured in 2 different series. In series 1, the radioactive IDeg (tracer) and surplus unlabeled IDeg are added to the sample. In series 2, the tracer and surplus unlabeled human insulin are added to the sample. Series 1 represents unspecific background binding. Series 2 represents IDeg specific antibodies including unspecific background binding. The reported %B/T is calculated by subtracting the background %B/T in series 1 from the %B/T result in series 2. If the background result has higher values than the %B/T in series 2, the resulting value is negative %B/T. Here, a negative %B/T value means that the test samples do not have IDeg-specific antibodies. The reason for getting a negative value for %B/T is due to variation in the analytical background. Thus, the results presented are not a change from baseline.	at week 52
Anti-drug Antibodies: Number of Participants Positive or Negative for Anti-liraglutide Antibodies	Anti-liraglutide antibodies were measured at week 52. Number of participants positive or negative for anti-liraglutide antibodies at week 52 were reported.	at week 52
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 52.	at screening (week -2 to week 0), at week 52
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 52.	at screening (week -2 to week 0), at week 52
Change in Clinical Evaluation: Pulse	Change in pulse after 52 weeks of treatment.	Week 0, week 52
Serum Concentrations of Insulin Degludec	Samples from the IDegLira and IDeg arms were analysed for serum concentrations of insulin degludec using validated ELISA assays.	Weeks 2, 8, 16, 26, 44, 52
Plasma Concentrations of Liraglutide	Samples from the IDegLira and liraglutide arms were assayed for plasma concentrations of liraglutide using validated ELISA assays.	Weeks 2, 8, 16, 26, 44, 52

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

General Publications

• Kaku K, Araki E, Tanizawa Y, Ross Agner B, Nishida T, Ranthe M, Inagaki N. Superior efficacy with a fixed-ratio combination of insulin degludec and liraglutide (IDegLira) compared with insulin degludec and liraglutide in insulin-naive Japanese patients with type 2 diabetes in a phase 3, open-label, randomized trial. Diabetes Obes Metab. 2019 Dec;21(12):2674-2683. doi: 10.1111/dom.13856. Epub 2019 Aug 28.
• 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.

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2015
• Primary Completion (Actual): December 15, 2017
• Study Completion (Actual): December 22, 2017

Study Registration Dates

• First Submitted: November 16, 2015
• First Submitted That Met QC Criteria: November 16, 2015
• First Posted (Estimate): November 18, 2015

Study Record Updates

• Last Update Posted (Actual): April 9, 2021
• Last Update Submitted That Met QC Criteria: March 10, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Insulin; Insulin, Globin Zinc; Insulin, Long-Acting; Liraglutide; Xultophy
• Other Study ID Numbers: NN9068-4183; U1111-1170-1332 (Other Identifier: WHO); JapicCTI-153089 (Other Identifier: JAPIC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No