DUAL™ II Japan: 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
Sponsor
Novo Nordisk A/S (Industry)
Overall Status
Completed
CT.gov ID
NCT02911948
Collaborator
(none)
210
38
2
14
5.5
0.4
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
210 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
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
Actual Study Start Date
:
Sep 21, 2016
Actual Primary Completion Date
:
Nov 17, 2017
Actual Study Completion Date
:
Nov 22, 2017
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Insulin degludec/liraglutide
|
Drug: Insulin degludec/liraglutide
Injected s.c. / subcutaneously (under the skin) once daily
|
| Active Comparator: Insulin degludec
|
Drug: Insulin degludec
Injected s.c. / subcutaneously (under the skin) once daily
|
Outcome Measures
Primary Outcome Measures
- Change in Glycosylated Haemoglobin (HbA1c) [week 0, week 26]
Change from baseline (week 0) in HbA1c after 26 weeks of treatment.
Secondary Outcome Measures
- Change in Body Weight [week 0, week 26]
Change from baseline (week 0) in body weight after 26 weeks of treatment.
- Change in Fasting Plasma Glucose (FPG) [week 0, week 26]
Change from baseline (week 0) in FPG after 26 weeks of treatment.
- Number of Treatment Emergent Severe or Blood Glucose (BG) Confirmed Hypoglycaemic Episodes [During 26 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 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 [After 26 weeks]
Actual daily total insulin dose after 26 weeks.
- Responder (Yes/no): HbA1c Less Than 7.0% [After 26 weeks]
Number of subjects with HbA1c less than 7.0% after 26 weeks.
- Responder (Yes/no): HbA1c Less Than 7.0% and Without Weight Gain [After 26 weeks]
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 [After 26 weeks]
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 [After 26 weeks]
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% [After 26 weeks]
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 [After 26 weeks]
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 [After 26 weeks]
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 [After 26 weeks]
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 [week 0, week 26]
Change from baseline (week 0) in waist circumference after 26 weeks of treatment.
- Change in Blood Pressure (Systolic and Diastolic) [week 0, week 26]
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) [After 26 weeks]
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 [Week 0, week 26]
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) [Week 0, week 26]
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 [Week 0, week 26]
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) [During 26 weeks of treatment]
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 [During 26 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 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 [During 26 weeks of treatment]
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 [During 26 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. 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 [Screening (week -2 to week 0), week 26]
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) [Screening (week -2 to week 0), week 26]
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 [Week 0, week 26]
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 [week 0, week 26]
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 [week 0, week 26]
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).
Eligibility Criteria
Criteria
Ages Eligible for Study:
20 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novo Nordisk Investigational Site | Asahikawa-shi, Hokkaido | Japan | 078-8211 | |
| 2 | Novo Nordisk Investigational Site | Chigasaki-shi, Kanagawa | Japan | 253-0044 | |
| 3 | Novo Nordisk Investigational Site | Chitose, Hokkaido | Japan | 066-0032 | |
| 4 | Novo Nordisk Investigational Site | Chiyoda-ku, Tokyo | Japan | 101-0024 | |
| 5 | Novo Nordisk Investigational Site | Fujisawa-shi, Kanagawa | Japan | 251-0041 | |
| 6 | Novo Nordisk Investigational Site | Fukui-shi, Fukui | Japan | 918-8503 | |
| 7 | Novo Nordisk Investigational Site | Fukuoka-shi, Fukuoka | Japan | 810-0001 | |
| 8 | Novo Nordisk Investigational Site | Fukuoka-shi, Fukuoka | Japan | 819-0006 | |
| 9 | Novo Nordisk Investigational Site | Fukuoka | Japan | 830 8522 | |
| 10 | Novo Nordisk Investigational Site | Fukushima | Japan | 963-8851 | |
| 11 | Novo Nordisk Investigational Site | Hokkaido | Japan | 060-0062 | |
| 12 | Novo Nordisk Investigational Site | Ibaraki | Japan | 311-0113 | |
| 13 | Novo Nordisk Investigational Site | Kanagawa | Japan | 235-0045 | |
| 14 | Novo Nordisk Investigational Site | Kashiwara-shi, Osaka | Japan | 582-0005 | |
| 15 | Novo Nordisk Investigational Site | Kawagoe-shi, Saitama | Japan | 350-0851 | |
| 16 | Novo Nordisk Investigational Site | Kawaguchi-shi, Saitama | Japan | 332-0012 | |
| 17 | Novo Nordisk Investigational Site | Kumamoto-shi, Kumamoto | Japan | 862-0965 | |
| 18 | Novo Nordisk Investigational Site | Kumamoto | Japan | 862-0976 | |
| 19 | Novo Nordisk Investigational Site | Mitaka-shi, Tokyo | Japan | 181-0013 | |
| 20 | Novo Nordisk Investigational Site | Miyazaki | Japan | 880-0034 | |
| 21 | Novo Nordisk Investigational Site | Nagano | Japan | 390-8621 | |
| 22 | Novo Nordisk Investigational Site | Nakagami, Okinawa | Japan | 901-2393 | |
| 23 | Novo Nordisk Investigational Site | Neyagawa-shi, Osaka | Japan | ||
| 24 | Novo Nordisk Investigational Site | Niigata-shi, Niigata | Japan | 950 1104 | |
| 25 | Novo Nordisk Investigational Site | Okawa-shi, Fukuoka | Japan | 831-0016 | |
| 26 | Novo Nordisk Investigational Site | Osaka-shi, Osaka | Japan | 536-0001 | |
| 27 | Novo Nordisk Investigational Site | Osaka | Japan | 569-1045 | |
| 28 | Novo Nordisk Investigational Site | Ota-ku, Tokyo | Japan | 1430015 | |
| 29 | Novo Nordisk Investigational Site | Saitama-shi, Saitama | Japan | 336-0967 | |
| 30 | Novo Nordisk Investigational Site | Sendai-shi, Miyagi | Japan | 980-0021 | |
| 31 | Novo Nordisk Investigational Site | Shimotsuke-shi, Tochigi | Japan | 329-0433 | |
| 32 | Novo Nordisk Investigational Site | Tochigi | Japan | 323-0022 | |
| 33 | Novo Nordisk Investigational Site | Tokyo | Japan | 103-0027 | |
| 34 | Novo Nordisk Investigational Site | Tokyo | Japan | 103-0028 | |
| 35 | Novo Nordisk Investigational Site | Tokyo | Japan | 113-8431 | |
| 36 | Novo Nordisk Investigational Site | Tomigusuku-shi, Okinawa | Japan | 901-0243 | |
| 37 | Novo Nordisk Investigational Site | Tomigusuku-shi, Okinawa | Japan | 901-0244 | |
| 38 | Novo Nordisk Investigational Site | Yamaguchi-shi, Yamaguchi | Japan | 754-0002 |
Sponsors and Collaborators
- Novo Nordisk A/S
Investigators
- Study Director: Global Clinical Registry (GCR, 1452), Novo Nordisk A/S
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT02911948
Other Study ID Numbers:
- NN9068-4184
- U1111-1178-3453
- JapicCTI-163385
First Posted:
Sep 23, 2016
Last Update Posted:
Apr 9, 2021
Last Verified:
Mar 1, 2021
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | The trial was conducted at 38 sites in Japan as follows: 38 sites screened and 37 sites randomised subjects. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec |
|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide), with the option of choosing up to 16 dose steps (16 units IDeg/0.6 mg liraglutide) at the investigator's discretion. IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDegLira was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. | Eligible subjects were treated with insulin degludec (IDeg) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDeg was 10 units IDeg, with the option of choosing up to 16 units IDeg at the investigator's discretion. IDeg was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 units IDeg, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDeg was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. |
| Period Title: Overall Study | ||
| STARTED | 105 | 105 |
| COMPLETED | 105 | 98 |
| NOT COMPLETED | 0 | 7 |
Baseline Characteristics
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec | Total |
|---|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide), with the option of choosing up to 16 dose steps (16 units IDeg/0.6 mg liraglutide) at the investigator's discretion. IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDegLira was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. | Eligible subjects were treated with insulin degludec (IDeg) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDeg was 10 units IDeg, with the option of choosing up to 16 units IDeg at the investigator's discretion. IDeg was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 units IDeg, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDeg was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. | Total of all reporting groups |
| Overall Participants | 105 | 105 | 210 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
56.6
(10.4)
|
55.5
(10.0)
|
56.0
(10.2)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
35
33.3%
|
42
40%
|
77
36.7%
|
| Male |
70
66.7%
|
63
60%
|
133
63.3%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
| Not Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
105
100%
|
105
100%
|
210
100%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
105
100%
|
105
100%
|
210
100%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
| White |
0
0%
|
0
0%
|
0
0%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Glycosylated Haemoglobin (HbA1c) (Percentage of HbA1c) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Percentage of HbA1c] |
8.61
(0.88)
|
8.56
(0.80)
|
8.58
(0.84)
|
Outcome Measures
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (210 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method. |
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec |
|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide), with the option of choosing up to 16 dose steps (16 units IDeg/0.6 mg liraglutide) at the investigator's discretion. IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDegLira was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. | Eligible subjects were treated with insulin degludec (IDeg) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDeg was 10 units IDeg, with the option of choosing up to 16 units IDeg at the investigator's discretion. IDeg was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 units IDeg, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDeg was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. |
| Measure Participants | 105 | 105 |
| Mean (Standard Deviation) [Percentage of HbA1c] |
-1.95
(1.01)
|
-0.65
(0.98)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Insulin Degludec/Liraglutide, Insulin Degludec |
|---|---|---|
| Comments | The response and change from baseline in response after 26 weeks are analysed using an ANCOVA model with treatment and pre-trial anti-diabetic treatment as fixed factors and corresponding baseline HbA1c value as covariate. | |
| Type of Statistical Test | Superiority | |
| Comments | Superiority was considered confirmed if the upper bound of the two-sided 95% confidence interval was strictly below 0.0% for null hypothesis (H0): D=0.0% against the alternative (HA): D≠0.0%, where D is the mean difference (IDegLira - IDeg). | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Treatment contrast |
| Estimated Value | -1.28 | |
| Confidence Interval |
(2-Sided) 95% -1.50 to -1.06 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (210 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method. |
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec |
|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide), with the option of choosing up to 16 dose steps (16 units IDeg/0.6 mg liraglutide) at the investigator's discretion. IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDegLira was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. | Eligible subjects were treated with insulin degludec (IDeg) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDeg was 10 units IDeg, with the option of choosing up to 16 units IDeg at the investigator's discretion. IDeg was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 units IDeg, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDeg was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. |
| Measure Participants | 105 | 105 |
| Mean (Standard Deviation) [Kg] |
-0.7
(3.5)
|
0.7
(2.7)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (210 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method. |
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec |
|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide), with the option of choosing up to 16 dose steps (16 units IDeg/0.6 mg liraglutide) at the investigator's discretion. IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDegLira was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. | Eligible subjects were treated with insulin degludec (IDeg) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDeg was 10 units IDeg, with the option of choosing up to 16 units IDeg at the investigator's discretion. IDeg was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 units IDeg, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDeg was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. |
| Measure Participants | 105 | 105 |
| Mean (Standard Deviation) [mmol/L] |
-2.81
(3.17)
|
-2.29
(2.68)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparator (210 subjects). Subjects in the safety set contributed to the evaluation "as treated". |
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec |
|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide), with the option of choosing up to 16 dose steps (16 units IDeg/0.6 mg liraglutide) at the investigator's discretion. IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDegLira was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. | Eligible subjects were treated with insulin degludec (IDeg) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDeg was 10 units IDeg, with the option of choosing up to 16 units IDeg at the investigator's discretion. IDeg was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 units IDeg, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDeg was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. |
| Measure Participants | 105 | 105 |
| Number [Number of episodes] |
124
|
109
|
| Title | Daily Insulin Dose |
|---|---|
| Description | Actual daily total insulin dose after 26 weeks. |
| Time Frame | After 26 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (210 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method. |
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec |
|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide), with the option of choosing up to 16 dose steps (16 units IDeg/0.6 mg liraglutide) at the investigator's discretion. IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDegLira was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. | Eligible subjects were treated with insulin degludec (IDeg) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDeg was 10 units IDeg, with the option of choosing up to 16 units IDeg at the investigator's discretion. IDeg was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 units IDeg, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDeg was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. |
| Measure Participants | 105 | 105 |
| Mean (Standard Deviation) [Units] |
37.6
(11.4)
|
41.2
(11.5)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (210 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method. |
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec |
|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide), with the option of choosing up to 16 dose steps (16 units IDeg/0.6 mg liraglutide) at the investigator's discretion. IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDegLira was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. | Eligible subjects were treated with insulin degludec (IDeg) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDeg was 10 units IDeg, with the option of choosing up to 16 units IDeg at the investigator's discretion. IDeg was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 units IDeg, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDeg was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. |
| Measure Participants | 105 | 105 |
| Yes |
75
71.4%
|
23
21.9%
|
| No |
30
28.6%
|
82
78.1%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (210 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method. |
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec |
|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide), with the option of choosing up to 16 dose steps (16 units IDeg/0.6 mg liraglutide) at the investigator's discretion. IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDegLira was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. | Eligible subjects were treated with insulin degludec (IDeg) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDeg was 10 units IDeg, with the option of choosing up to 16 units IDeg at the investigator's discretion. IDeg was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 units IDeg, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDeg was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. |
| Measure Participants | 105 | 105 |
| Yes |
50
47.6%
|
9
8.6%
|
| No |
55
52.4%
|
96
91.4%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (210 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method. Number Analyzed = subjects with available data. |
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec |
|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide), with the option of choosing up to 16 dose steps (16 units IDeg/0.6 mg liraglutide) at the investigator's discretion. IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDegLira was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. | Eligible subjects were treated with insulin degludec (IDeg) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDeg was 10 units IDeg, with the option of choosing up to 16 units IDeg at the investigator's discretion. IDeg was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 units IDeg, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDeg was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. |
| Measure Participants | 105 | 101 |
| Yes |
70
66.7%
|
20
19%
|
| No |
35
33.3%
|
81
77.1%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (210 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method. Number Analyzed = subjects with available data. |
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec |
|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide), with the option of choosing up to 16 dose steps (16 units IDeg/0.6 mg liraglutide) at the investigator's discretion. IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDegLira was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. | Eligible subjects were treated with insulin degludec (IDeg) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDeg was 10 units IDeg, with the option of choosing up to 16 units IDeg at the investigator's discretion. IDeg was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 units IDeg, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDeg was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. |
| Measure Participants | 105 | 101 |
| Yes |
49
46.7%
|
7
6.7%
|
| No |
56
53.3%
|
94
89.5%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (210 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method. |
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec |
|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide), with the option of choosing up to 16 dose steps (16 units IDeg/0.6 mg liraglutide) at the investigator's discretion. IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDegLira was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. | Eligible subjects were treated with insulin degludec (IDeg) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDeg was 10 units IDeg, with the option of choosing up to 16 units IDeg at the investigator's discretion. IDeg was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 units IDeg, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDeg was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. |
| Measure Participants | 105 | 105 |
| Yes |
57
54.3%
|
9
8.6%
|
| No |
48
45.7%
|
96
91.4%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (210 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method. |
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec |
|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide), with the option of choosing up to 16 dose steps (16 units IDeg/0.6 mg liraglutide) at the investigator's discretion. IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDegLira was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. | Eligible subjects were treated with insulin degludec (IDeg) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDeg was 10 units IDeg, with the option of choosing up to 16 units IDeg at the investigator's discretion. IDeg was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 units IDeg, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDeg was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. |
| Measure Participants | 105 | 105 |
| Yes |
38
36.2%
|
4
3.8%
|
| No |
67
63.8%
|
101
96.2%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (210 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method. Number Analyzed = subjects with available data. |
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec |
|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide), with the option of choosing up to 16 dose steps (16 units IDeg/0.6 mg liraglutide) at the investigator's discretion. IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDegLira was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. | Eligible subjects were treated with insulin degludec (IDeg) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDeg was 10 units IDeg, with the option of choosing up to 16 units IDeg at the investigator's discretion. IDeg was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 units IDeg, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDeg was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. |
| Measure Participants | 105 | 101 |
| Yes |
53
50.5%
|
8
7.6%
|
| No |
52
49.5%
|
93
88.6%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (210 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method. Number Analyzed = subjects with available data. |
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec |
|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide), with the option of choosing up to 16 dose steps (16 units IDeg/0.6 mg liraglutide) at the investigator's discretion. IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDegLira was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. | Eligible subjects were treated with insulin degludec (IDeg) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDeg was 10 units IDeg, with the option of choosing up to 16 units IDeg at the investigator's discretion. IDeg was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 units IDeg, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDeg was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. |
| Measure Participants | 105 | 101 |
| Yes |
37
35.2%
|
3
2.9%
|
| No |
68
64.8%
|
98
93.3%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (210 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method. |
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec |
|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide), with the option of choosing up to 16 dose steps (16 units IDeg/0.6 mg liraglutide) at the investigator's discretion. IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDegLira was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. | Eligible subjects were treated with insulin degludec (IDeg) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDeg was 10 units IDeg, with the option of choosing up to 16 units IDeg at the investigator's discretion. IDeg was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 units IDeg, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDeg was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. |
| Measure Participants | 105 | 105 |
| Mean (Standard Deviation) [cm] |
-0.6
(3.8)
|
0.1
(3.8)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (210 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method. |
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec |
|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide), with the option of choosing up to 16 dose steps (16 units IDeg/0.6 mg liraglutide) at the investigator's discretion. IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDegLira was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. | Eligible subjects were treated with insulin degludec (IDeg) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDeg was 10 units IDeg, with the option of choosing up to 16 units IDeg at the investigator's discretion. IDeg was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 units IDeg, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDeg was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. |
| Measure Participants | 105 | 105 |
| Systolic blood pressure |
-0.6
(14.7)
|
0.9
(13.6)
|
| Diastolic blood pressure |
0.9
(9.0)
|
1.2
(9.0)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (210 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method. Number Analyzed = subjects with available data. |
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec |
|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide), with the option of choosing up to 16 dose steps (16 units IDeg/0.6 mg liraglutide) at the investigator's discretion. IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDegLira was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. | Eligible subjects were treated with insulin degludec (IDeg) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDeg was 10 units IDeg, with the option of choosing up to 16 units IDeg at the investigator's discretion. IDeg was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 units IDeg, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDeg was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. |
| Measure Participants | 105 | 105 |
| Before breakfast |
6.59
(2.32)
|
6.53
(2.19)
|
| 90 minutes after start of breakfast |
11.00
(3.67)
|
12.02
(3.57)
|
| Before lunch |
7.22
(2.96)
|
8.49
(3.75)
|
| 90 minutes after start of lunch |
10.59
(3.17)
|
12.84
(3.65)
|
| Before dinner |
7.39
(2.56)
|
8.60
(3.97)
|
| 90 minutes after start of dinner |
11.09
(3.24)
|
13.27
(4.05)
|
| At Bedtime |
9.57
(3.54)
|
11.98
(4.17)
|
| At 4:00 a.m. |
6.75
(1.98)
|
7.72
(2.90)
|
| Before breakfast the following day |
6.14
(1.68)
|
6.40
(2.06)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (210 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method. Number Analyzed = subjects with available data. |
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec |
|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide), with the option of choosing up to 16 dose steps (16 units IDeg/0.6 mg liraglutide) at the investigator's discretion. IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDegLira was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. | Eligible subjects were treated with insulin degludec (IDeg) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDeg was 10 units IDeg, with the option of choosing up to 16 units IDeg at the investigator's discretion. IDeg was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 units IDeg, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDeg was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. |
| Measure Participants | 104 | 105 |
| Mean (Standard Deviation) [mmol/L] |
-2.90
(2.87)
|
-1.11
(2.68)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (210 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method. |
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec |
|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide), with the option of choosing up to 16 dose steps (16 units IDeg/0.6 mg liraglutide) at the investigator's discretion. IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDegLira was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. | Eligible subjects were treated with insulin degludec (IDeg) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDeg was 10 units IDeg, with the option of choosing up to 16 units IDeg at the investigator's discretion. IDeg was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 units IDeg, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDeg was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. |
| Measure Participants | 105 | 105 |
| Mean (Standard Deviation) [mmol/L] |
-0.76
(3.00)
|
0.70
(2.93)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (210 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method. Number analyzed = subjects with available data. |
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec |
|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide), with the option of choosing up to 16 dose steps (16 units IDeg/0.6 mg liraglutide) at the investigator's discretion. IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDegLira was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. | Eligible subjects were treated with insulin degludec (IDeg) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDeg was 10 units IDeg, with the option of choosing up to 16 units IDeg at the investigator's discretion. IDeg was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 units IDeg, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDeg was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. |
| Measure Participants | 105 | 105 |
| Total cholesterol |
0.90
(15.9)
|
0.96
(13.0)
|
| HDL cholesterol |
0.90
(17.5)
|
0.95
(12.2)
|
| LDL cholesterol |
0.86
(26.7)
|
0.95
(21.5)
|
| VLDL cholesterol |
1.02
(50.5)
|
0.97
(38.2)
|
| Triglycerides |
1.02
(58.5)
|
0.97
(39.3)
|
| Free fatty acids |
0.86
(67.7)
|
0.77
(55.3)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparator (210 subjects). Subjects in the safety set contributed to the evaluation "as treated". |
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec |
|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide), with the option of choosing up to 16 dose steps (16 units IDeg/0.6 mg liraglutide) at the investigator's discretion. IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDegLira was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. | Eligible subjects were treated with insulin degludec (IDeg) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDeg was 10 units IDeg, with the option of choosing up to 16 units IDeg at the investigator's discretion. IDeg was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 units IDeg, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDeg was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. |
| Measure Participants | 105 | 105 |
| Number [Number of events] |
280
|
210
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparator (210 subjects). Subjects in the safety set contributed to the evaluation "as treated". |
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec |
|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide), with the option of choosing up to 16 dose steps (16 units IDeg/0.6 mg liraglutide) at the investigator's discretion. IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDegLira was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. | Eligible subjects were treated with insulin degludec (IDeg) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDeg was 10 units IDeg, with the option of choosing up to 16 units IDeg at the investigator's discretion. IDeg was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 units IDeg, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDeg was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. |
| Measure Participants | 105 | 105 |
| Number [Number of episodes] |
52
|
43
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparator (210 subjects). Subjects in the safety set contributed to the evaluation "as treated". |
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec |
|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide), with the option of choosing up to 16 dose steps (16 units IDeg/0.6 mg liraglutide) at the investigator's discretion. IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDegLira was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. | Eligible subjects were treated with insulin degludec (IDeg) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDeg was 10 units IDeg, with the option of choosing up to 16 units IDeg at the investigator's discretion. IDeg was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 units IDeg, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDeg was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. |
| Measure Participants | 105 | 105 |
| Number [Number of episodes] |
780
|
717
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparator (210 subjects). Subjects in the safety set contributed to the evaluation "as treated". |
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec |
|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide), with the option of choosing up to 16 dose steps (16 units IDeg/0.6 mg liraglutide) at the investigator's discretion. IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDegLira was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. | Eligible subjects were treated with insulin degludec (IDeg) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDeg was 10 units IDeg, with the option of choosing up to 16 units IDeg at the investigator's discretion. IDeg was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 units IDeg, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDeg was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. |
| Measure Participants | 105 | 105 |
| Number [Number of episodes] |
4
|
8
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparator (210 subjects). Subjects in the safety set contributed to the evaluation "as treated". Missing data were imputed using last observation carried forward (LOCF) method. |
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec |
|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide), with the option of choosing up to 16 dose steps (16 units IDeg/0.6 mg liraglutide) at the investigator's discretion. IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDegLira was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. | Eligible subjects were treated with insulin degludec (IDeg) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDeg was 10 units IDeg, with the option of choosing up to 16 units IDeg at the investigator's discretion. IDeg was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 units IDeg, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDeg was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. |
| Measure Participants | 105 | 105 |
| Left eye - at screening visit - normal |
53
50.5%
|
70
66.7%
|
| Left eye - at screening visit - Abn, NCS |
6
5.7%
|
5
4.8%
|
| Left eye - at screening visit - Abn, CS |
46
43.8%
|
30
28.6%
|
| Left eye - week 26 - normal |
54
51.4%
|
64
61%
|
| Left eye - week 26 - Abn, NCS |
7
6.7%
|
7
6.7%
|
| Left eye - week 26 - Abn, CS |
44
41.9%
|
34
32.4%
|
| Right eye - at screening visit - normal |
55
52.4%
|
72
68.6%
|
| Right eye - at screening visit - Abn, NCS |
7
6.7%
|
6
5.7%
|
| Right eye - at screening visit - Abn, CS |
43
41%
|
27
25.7%
|
| Right eye - week 26 - normal |
52
49.5%
|
69
65.7%
|
| Right eye - week 26 - Abn, NCS |
8
7.6%
|
6
5.7%
|
| Right eye - week 26 - Abn, CS |
45
42.9%
|
30
28.6%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparator (210 subjects). Subjects in the safety set contributed to the evaluation "as treated". Missing data were imputed using last observation carried forward (LOCF) method. |
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec |
|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide), with the option of choosing up to 16 dose steps (16 units IDeg/0.6 mg liraglutide) at the investigator's discretion. IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDegLira was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. | Eligible subjects were treated with insulin degludec (IDeg) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDeg was 10 units IDeg, with the option of choosing up to 16 units IDeg at the investigator's discretion. IDeg was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 units IDeg, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDeg was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. |
| Measure Participants | 105 | 105 |
| At screening visit - normal |
80
76.2%
|
82
78.1%
|
| At screening visit - Abn, NCS |
20
19%
|
18
17.1%
|
| At screening visit - Abn, CS |
5
4.8%
|
5
4.8%
|
| Week 26 -normal |
82
78.1%
|
82
78.1%
|
| Week 26 - Abn, NCS |
17
16.2%
|
20
19%
|
| Week 26 - Abn, CS |
6
5.7%
|
3
2.9%
|
| Title | Change in Pulse |
|---|---|
| Description | Change in pulse after 26 weeks of treatment. |
| Time Frame | Week 0, week 26 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparator (210 subjects). Missing data were imputed using last observation carried forward (LOCF) method. |
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec |
|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide), with the option of choosing up to 16 dose steps (16 units IDeg/0.6 mg liraglutide) at the investigator's discretion. IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDegLira was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. | Eligible subjects were treated with insulin degludec (IDeg) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDeg was 10 units IDeg, with the option of choosing up to 16 units IDeg at the investigator's discretion. IDeg was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 units IDeg, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDeg was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. |
| Measure Participants | 105 | 105 |
| Mean (Standard Deviation) [beats per minute] |
6.1
(11.0)
|
-0.2
(7.1)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (210 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method. |
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec |
|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide), with the option of choosing up to 16 dose steps (16 units IDeg/0.6 mg liraglutide) at the investigator's discretion. IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDegLira was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. | Eligible subjects were treated with insulin degludec (IDeg) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDeg was 10 units IDeg, with the option of choosing up to 16 units IDeg at the investigator's discretion. IDeg was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 units IDeg, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDeg was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. |
| Measure Participants | 105 | 105 |
| Total score |
7.9
(14.8)
|
0.1
(13.4)
|
| Burden on social activities and daily activities |
5.7
(17.3)
|
0.6
(17.1)
|
| Anxiety and dissatisfaction with treatment |
12.9
(20.8)
|
0.4
(17.2)
|
| Hypoglycaemia |
-2.6
(25.5)
|
-1.6
(25.9)
|
| Satisfaction with treatment |
15.8
(22.5)
|
-0.4
(24.7)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (210 subjects). The statistical evaluation of the FAS followed the intention-to-treat (ITT) principle and subjects contributed to the evaluation "as randomised". Missing data were imputed using last observation carried forward (LOCF) method. |
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec |
|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide), with the option of choosing up to 16 dose steps (16 units IDeg/0.6 mg liraglutide) at the investigator's discretion. IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDegLira was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. | Eligible subjects were treated with insulin degludec (IDeg) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDeg was 10 units IDeg, with the option of choosing up to 16 units IDeg at the investigator's discretion. IDeg was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 units IDeg, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDeg was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. |
| Measure Participants | 105 | 105 |
| Change in VAS score |
6.3
(17.8)
|
-1.0
(15.5)
|
| Index score |
0.02
(0.08)
|
-0.01
(0.11)
|
Adverse Events
| Time Frame | Week 0 (randomisation) to week 26 (end of treatment) and 7 days after end of treatment. | |||
|---|---|---|---|---|
| Adverse Event Reporting 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. | |||
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec | ||
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide), with the option of choosing up to 16 dose steps (16 units IDeg/0.6 mg liraglutide) at the investigator's discretion. IDegLira was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 dose steps (50 units IDeg/1.8 mg liraglutide), aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDegLira was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. | Eligible subjects were treated with insulin degludec (IDeg) in combination with metformin (at stable pre-trial dose and frequency level) for 26 weeks. The starting dose of IDeg was 10 units IDeg, with the option of choosing up to 16 units IDeg at the investigator's discretion. IDeg was titrated twice weekly according to a predefined titration algorithm to a maximum of 50 units IDeg, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). IDeg was injected subcutaneously (s.c.), once daily (OD) in the thigh, upper arm (deltoid region) or abdomen. One follow-up contact was scheduled at least 7 to 10 days after end of treatment. | ||
All Cause Mortality |
||||
| Insulin Degludec/Liraglutide | Insulin Degludec | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/105 (0%) | 0/105 (0%) | ||
Serious Adverse Events |
||||
| Insulin Degludec/Liraglutide | Insulin Degludec | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/105 (2.9%) | 4/105 (3.8%) | ||
| Cardiac disorders | ||||
| Acute myocardial infarction | 1/105 (1%) | 1 | 0/105 (0%) | 0 |
| Cardiac failure congestive | 1/105 (1%) | 1 | 0/105 (0%) | 0 |
| Eye disorders | ||||
| Retinal detachment | 0/105 (0%) | 0 | 1/105 (1%) | 1 |
| Hepatobiliary disorders | ||||
| Cholecystitis acute | 0/105 (0%) | 0 | 1/105 (1%) | 1 |
| Infections and infestations | ||||
| Gastroenteritis | 1/105 (1%) | 1 | 0/105 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||
| Hip fracture | 1/105 (1%) | 1 | 0/105 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Pancreatic carcinoma | 0/105 (0%) | 0 | 1/105 (1%) | 1 |
| Renal cell carcinoma | 0/105 (0%) | 0 | 1/105 (1%) | 1 |
| Nervous system disorders | ||||
| Loss of consciousness | 0/105 (0%) | 0 | 1/105 (1%) | 2 |
Other (Not Including Serious) Adverse Events |
||||
| Insulin Degludec/Liraglutide | Insulin Degludec | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 54/105 (51.4%) | 48/105 (45.7%) | ||
| Eye disorders | ||||
| Diabetic retinopathy | 17/105 (16.2%) | 18 | 17/105 (16.2%) | 18 |
| Gastrointestinal disorders | ||||
| Abdominal discomfort | 8/105 (7.6%) | 8 | 5/105 (4.8%) | 5 |
| Constipation | 9/105 (8.6%) | 10 | 4/105 (3.8%) | 4 |
| Diarrhoea | 15/105 (14.3%) | 20 | 5/105 (4.8%) | 6 |
| Nausea | 10/105 (9.5%) | 12 | 4/105 (3.8%) | 5 |
| Vomiting | 9/105 (8.6%) | 11 | 2/105 (1.9%) | 2 |
| Infections and infestations | ||||
| Viral upper respiratory tract infection | 21/105 (20%) | 27 | 24/105 (22.9%) | 30 |
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 8/105 (7.6%) | 8 | 0/105 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
At the end of the trial, one or more scientific publications may be prepared collaboratively by the investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for up to 60 days to protect intellectual property
Results Point of Contact
| Name/Title | Clinical Reporting Anchor and Disclosure (1452) |
|---|---|
| Organization | Novo Nordisk A/S |
| Phone | (+1) 866-867-7178 |
| clinicaltrials@novonordisk.com |
Responsible Party:
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT02911948
Other Study ID Numbers:
- NN9068-4184
- U1111-1178-3453
- JapicCTI-163385
First Posted:
Sep 23, 2016
Last Update Posted:
Apr 9, 2021
Last Verified:
Mar 1, 2021