DUAL™ I Japan: A Trial Comparing the Efficacy and Safety of Insulin Degludec/Liraglutide, Insulin Degludec and Liraglutide in Japanese Subjects With Type 2 Diabetes Mellitus.
Sponsor
Novo Nordisk A/S (Industry)
Overall Status
Completed
CT.gov ID
NCT02607306
Collaborator
(none)
819
76
3
25.1
10.8
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, insulin degludec and liraglutide in Japanese subjects with type 2 diabetes mellitus.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
819 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Trial Comparing the Efficacy and Safety of Insulin Degludec/Liraglutide, Insulin Degludec and Liraglutide in Japanese Subjects With Type 2 Diabetes Mellitus
Actual Study Start Date
:
Nov 18, 2015
Actual Primary Completion Date
:
Dec 15, 2017
Actual Study Completion Date
:
Dec 22, 2017
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Insulin degludec/liraglutide OD
|
Drug: insulin degludec/liraglutide
Injected s.c. / subcutaneously (under the skin) once daily (OD) , in combination with pre-trial OAD (oral antidiabetic drug)kept in unchanged dose.
|
| Active Comparator: Insulin degludec OD
|
Drug: insulin degludec
Injected s.c. / subcutaneously (under the skin) once daily (OD) , in combination with pre-trial OAD (oral antidiabetic drug)kept in unchanged dose.
|
| Active Comparator: Liraglutide OD
|
Drug: liraglutide
Injected s.c. / subcutaneously (under the skin) once daily (OD) , in combination with pre-trial OAD (oral antidiabetic drug)kept in unchanged dose.
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline in HbA1c (Glycosylated Haemoglobin) Tested for Non-inferiority of IDegLira vs IDeg and Superiority of IDegLira vs Lira [Week 0, Week 52]
Change from baseline (week 0) in HbA1c after 52 weeks of treatment was measured. Statistical analyses were performed to test the hypotheses: non-inferiority of IDegLira vs. IDeg and superiority of IDegLira vs. Liraglutide (Lira).
Secondary Outcome Measures
- Change From Baseline in Body Weight (kg) [Week 0, Week 52]
Change from baseline (week 0) in body weight after 52 weeks of treatment.
- Number of Treatment Emergent Severe or Blood Glucose (BG) Confirmed Hypoglycaemic Episodes [Weeks 0-52]
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.
- Change From Baseline in HbA1c (Glycosylated Haemoglobin) Tested for Superiority of IDegLira vs IDeg [Week 0, Week 52]
Change from baseline (week 0) in HbA1c after 52 weeks of treatment was measured. Statistical analysis was performed to test the hypothesis: superiority of IDegLira vs. IDeg.
- Change From Baseline in Fasting Plasma Glucose (FPG) [Week 0, Week 52]
Change from baseline (week 0) in FPG after 52 weeks
- Insulin Dose [After 52 weeks of treatment]
Actual daily total insulin dose after 52 weeks of treatment.
- Responder (Yes/no): HbA1c Less Than 7.0% [After 52 weeks of treatment]
Number of subjects with HbA1c less than 7.0% after 52 weeks of treatment.
- Responder (Yes/no): HbA1c Less Than 7.0% and Change in Body Weight From Baseline Below or Equal to Zero [After 52 weeks of treatment]
Number of subjects with HbA1c less than 7.0% and without weight gain after 52 weeks of treatment.
- Responder (Yes/no): HbA1c Less Than 7.0% Without Treatment Emergent Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemic Episodes During the Last 12 Weeks of Treatment. [After 52 weeks of treatment]
Number of subjects with HbA1c less than 7.0% after 52 weeks, who did not experience treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes during the last 12 weeks of treatment. Treatment emergent hypoglycaemic episode is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Severe or BG confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification or BG confirmed by a plasma glucose value < 3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.
- Responder (Yes/no): HbA1c Less Than 7.0% and Change in Body Weight From Baseline Below or Equal to Zero and Without Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During the Last 12 Weeks of Treatment [After 52 weeks of treatment]
Number of subjects with HbA1c less than 7.0% and without weight gain, who did not experience treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes during the last 12 weeks of treatment. Treatment emergent hypoglycaemic episode is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Severe or BG confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification or BG confirmed by a plasma glucose value < 3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.
- Responder (Yes/no): HbA1c Less Than 6.5% [After 52 weeks of treatment]
Number of subjects with HbA1c less than 6.5% after 52 weeks of treatment.
- Responder (Yes/no): HbA1c Less Than 6.5% and Change in Body Weight From Baseline Below or Equal to Zero [After 52 weeks of treatment]
Number of subjects with HbA1c less than 6.5% and without weight gain after 52 weeks of treatment.
- Responder (Yes/no): HbA1c Less Than 6.5% Without Treatment Emergent Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemic Episodes During the Last 12 Weeks of Treatment. [After 52 weeks of treatment]
Number of subjects with HbA1c less than 6.5% after 52 weeks, who did not experience treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes during the last 12 weeks of treatment. Treatment emergent hypoglycaemic episode is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Severe or BG confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification or BG confirmed by a plasma glucose value < 3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.
- Responder (Yes/no): HbA1c Less Than 6.5% and Change in Body Weight From Baseline Below or Equal to Zero and Without Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During the Last 12 Weeks of Treatment [After 52 weeks of treatment]
Number of subjects with HbA1c less than 6.5% with no weight gain, who did not experience treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes during the last 12 weeks of treatment. Treatment emergent hypoglycaemic episode is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Severe or BG confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification or BG confirmed by a plasma glucose value < 3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.
- Change in Waist Circumference [Week 0, Week 52]
Change from baseline (week 0) in waist circumference after 52 weeks of treatment.
- Change in Blood Pressure (Systolic and Diastolic) [Week 0, Week 52]
Change from baseline in blood pressure (systolic and diastolic) after 52 weeks of treatment.
- Self-Measured Blood Glucose (SMBG) 9-point Profile: 9-point Profile (Individual Points in the Profile) [After 52 weeks of the treatment]
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 52]
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 Increments (From Before Meal to 90 Min After for Breakfast, Lunch and Dinner) [Week 0, week 52]
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.
- Total Cholesterol as a Ratio to Baseline at 52 Weeks [After 52 weeks of treatment]
Total cholesterol after 52 weeks of treatment was represented as ratio to baseline (week 0) values.
- Low Density Lipoprotein (LDL) Cholesterol as a Ratio to Baseline at 52 Weeks [After 52 weeks of treatment]
Low density lipoprotein (LDL) cholesterol after 52 weeks of treatment was represented as ratio to baseline (week 0) values.
- High Density Lipoprotein (HDL) Cholesterol as a Ratio to Baseline at 52 Weeks [After 52 weeks of treatment]
High density lipoprotein (HDL) cholesterol after 52 weeks of treatment was represented as ratio to baseline (week 0) values.
- Very Low Density Lipoprotein (VLDL) Cholesterol as a Ratio to Baseline at 52 Weeks [After 52 weeks of treatment]
Very low density lipoprotein (VLDL) cholesterol after 52 weeks of treatment was represented as ratio to baseline (week 0) values.
- Triglycerides as a Ratio to Baseline at 52 Weeks [After 52 weeks of treatment]
Triglycerides after 52 weeks of treatment was represented as ratio to baseline (week 0) values.
- Free Fatty Acids as a Ratio to Baseline at 52 Weeks [After 52 weeks of treatment]
Free fatty acids after 52 weeks of treatment was represented as ratio to baseline (week 0) values.
- Fasting C-peptide as a Ratio to Baseline at 52 Weeks [After 52 weeks of treatment]
Fasting C-peptide after 52 weeks of treatment was represented as ratio to baseline (week 0) values.
- Fasting Human Insulin as a Ratio to Baseline at 52 Weeks [After 52 weeks of treatment]
Fasting human insulin after 52 weeks of treatment was represented as ratio to baseline (week 0) values.
- Fasting Glucagon as a Ratio to Baseline at 52 Weeks [After 52 weeks of treatment]
Fasting glucagon after 52 weeks of treatment was represented as ratio to baseline (week 0) values.
- Proinsulin as a Ratio to Baseline at 52 Weeks [After 52 weeks of treatment]
Proinsulin after 52 weeks of treatment was represented as ratio to baseline (week 0) values.
- Number of Treatment Emergent Adverse Events (TEAEs) [0-52 weeks]
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 Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemic Episodes [0-52 weeks]
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 Nocturnal Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes [0-52 weeks]
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.
- Number of Treatment Emergent Hypoglycaemic Episodes According to American Diabetes Association (ADA) Definition [0-52 weeks]
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.
- Anti-drug Antibodies: Anti-insulin Degludec Antibodies [at week 52]
Insulin degludec (IDeg)-specific antibodies were measured at week 52, as %B/T (percentage of bound & precipitated radioactive drug/total added drug to the sample). A sample is measured in 2 different series. In series 1, the radioactive IDeg (tracer) and surplus unlabeled IDeg are added to the sample. In series 2, the tracer and surplus unlabeled human insulin are added to the sample. Series 1 represents unspecific background binding. Series 2 represents IDeg specific antibodies including unspecific background binding. The reported %B/T is calculated by subtracting the background %B/T in series 1 from the %B/T result in series 2. If the background result has higher values than the %B/T in series 2, the resulting value is negative %B/T. Here, a negative %B/T value means that the test samples do not have IDeg-specific antibodies. The reason for getting a negative value for %B/T is due to variation in the analytical background. Thus, the results presented are not a change from baseline.
- Anti-drug Antibodies: Number of Participants Positive or Negative for Anti-liraglutide Antibodies [at week 52]
Anti-liraglutide antibodies were measured at week 52. Number of participants positive or negative for anti-liraglutide antibodies at week 52 were reported.
- Change in Clinical Evaluation: Fundoscopy or Fundus Photography [at screening (week -2 to week 0), at week 52]
The result of the fundus photography/dilated fundoscopy was interpreted by the investigator into following categories: Normal; Abnormal (Abn), Not Clinically significant (NCS); Abnormal, Clinically significant (CS). Reported results are number of subjects with 'normal'; 'Abn, NCS' and 'Abn, CS' fundoscopy/fundus photography results at screening (week -2 to week 0) and week 52.
- Change in Clinical Evaluation: Electrocardiogram (ECG) [at screening (week -2 to week 0), at week 52]
The result of the ECG was interpreted by the investigator into following categories: Normal; Abnormal (Abn), Not Clinically significant (NCS); Abnormal, Clinically significant (CS). Reported results are number of subjects with 'normal'; 'Abn, NCS' and 'Abn, CS' ECG results at screening (week -2 to week 0) and week 52.
- Change in Clinical Evaluation: Pulse [Week 0, week 52]
Change in pulse after 52 weeks of treatment.
- Serum Concentrations of Insulin Degludec [Weeks 2, 8, 16, 26, 44, 52]
Samples from the IDegLira and IDeg arms were analysed for serum concentrations of insulin degludec using validated ELISA assays.
- Plasma Concentrations of Liraglutide [Weeks 2, 8, 16, 26, 44, 52]
Samples from the IDegLira and liraglutide arms were assayed for plasma concentrations of liraglutide using validated ELISA assays.
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
-
Type 2 diabetes subjects (diagnosed clinically) at least 6 months prior to screening
-
HbA1c (glycosylated haemoglobin) 7.0-11.0 % (both inclusive) by central laboratory analysis, with the aim of a median of 8.3%. When approximately 50% of the randomised subjects have a HbA1c above 8.3%, the remaining subjects randomised must have a HbA1c below or equal to 8.3%; or when approximately 50% of the randomised subjects have a HbA1c below or equal to 8.3%, the remaining subjects randomised must have a HbA1c above 8.3%
-
Body-mass index (BMI) above or equal to 20 kg/m^2
-
Subjects on stable therapy with one OAD (defined as unchanged medication and unchanged dose) for at least 60 days (metformin, a-GI, TZD, SU, SGLT2i or glinide) prior to screening according to approved Japanese labelling
Exclusion Criteria:
-
Previous treatment with insulin (except for short-term treatment in connection with intercurrent illness including gestational diabetes)
-
Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria in a period of 60 days before screening
-
Anticipated initiation or change in concomitant medications in excess of 14 days known to affect weight or glucose metabolism
-
Impaired liver function, defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) equal to or above 2.5 times upper limit of normal
-
Renal impairment estimated Glomerular Filtration Rate (eGFR) below 60mL/min/1.73m^2 as per Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
-
Screening calcitonin equal to or above 50 ng/L
-
History of pancreatitis (acute or chronic)
-
Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN 2)
-
Subjects presently classified as being in New York Heart Association (NYHA) Class IV
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novo Nordisk Investigational Site | Adachi-ku, Tokyo | Japan | 123-0845 | |
| 2 | Novo Nordisk Investigational Site | Akita-shi, Akita | Japan | 010-8543 | |
| 3 | Novo Nordisk Investigational Site | Annaka-shi, Gunma | Japan | 379-0116 | |
| 4 | Novo Nordisk Investigational Site | Asahikawa-shi, Hokkaido | Japan | 070-0002 | |
| 5 | Novo Nordisk Investigational Site | Chiba-shi, Chiba | Japan | 260-0804 | |
| 6 | Novo Nordisk Investigational Site | Chitose, Hokkaido | Japan | 066-0032 | |
| 7 | Novo Nordisk Investigational Site | Chuo-ku, Tokyo | Japan | 103-0002 | |
| 8 | Novo Nordisk Investigational Site | Chuo-ku,Tokyo | Japan | 103-0025 | |
| 9 | Novo Nordisk Investigational Site | Chuo-ku, | Japan | 104 0061 | |
| 10 | Novo Nordisk Investigational Site | Edogawa-ku, Tokyo | Japan | 134-0084 | |
| 11 | Novo Nordisk Investigational Site | Fujisawa-shi, Kanagawa | Japan | 251-0041 | |
| 12 | Novo Nordisk Investigational Site | Fukuoka-shi, Fukuoka | Japan | 819-0168 | |
| 13 | Novo Nordisk Investigational Site | Fukushima | Japan | 963-8851 | |
| 14 | Novo Nordisk Investigational Site | Gunma | Japan | 373-0036 | |
| 15 | Novo Nordisk Investigational Site | Hachioji-shi, Tokyo | Japan | 192-0917 | |
| 16 | Novo Nordisk Investigational Site | Hokkaido | Japan | 060-0062 | |
| 17 | Novo Nordisk Investigational Site | Hokkaido | Japan | 078-8236 | |
| 18 | Novo Nordisk Investigational Site | Ibaraki | Japan | 311-0113 | |
| 19 | Novo Nordisk Investigational Site | Ichihara-shi, Chiba | Japan | 290-0003 | |
| 20 | Novo Nordisk Investigational Site | Iruma-shi, Saitama | Japan | 358-0011 | |
| 21 | Novo Nordisk Investigational Site | Itabashi-ku, Tokyo | Japan | 173-0004 | |
| 22 | Novo Nordisk Investigational Site | Itabashi-ku, Tokyo | Japan | 175-0093 | |
| 23 | Novo Nordisk Investigational Site | Izumisano-shi,Osaka | Japan | 598-8577 | |
| 24 | Novo Nordisk Investigational Site | Izumisano-shi | Japan | 598 0048 | |
| 25 | Novo Nordisk Investigational Site | Kagoshima-shi, Kagoshima | Japan | 890-0061 | |
| 26 | Novo Nordisk Investigational Site | Kamakura-shi | Japan | 247 0056 | |
| 27 | Novo Nordisk Investigational Site | Kanagawa | Japan | 235-0045 | |
| 28 | Novo Nordisk Investigational Site | Kanra-gun, Gunma | Japan | 370-2214 | |
| 29 | Novo Nordisk Investigational Site | Kashiwara-shi, Osaka | Japan | 582-0005 | |
| 30 | Novo Nordisk Investigational Site | Kawagoe-shi, Saitama | Japan | 350-0851 | |
| 31 | Novo Nordisk Investigational Site | Kawaguchi-shi, Saitama | Japan | 332-0012 | |
| 32 | Novo Nordisk Investigational Site | Kawasaki-shi,Kanagawa | Japan | 215-0026 | |
| 33 | Novo Nordisk Investigational Site | Kisarazu-shi, Chiba | Japan | 292-0038 | |
| 34 | Novo Nordisk Investigational Site | Kobe-shi, Hyogo | Japan | ||
| 35 | Novo Nordisk Investigational Site | Kuki-shi, Saitama | Japan | 346-8530 | |
| 36 | Novo Nordisk Investigational Site | Kumamoto-shi, Kumamoto | Japan | 860-0811 | |
| 37 | Novo Nordisk Investigational Site | Kumamoto-shi, Kumamoto | Japan | 861-8039 | |
| 38 | Novo Nordisk Investigational Site | Kumamoto | Japan | 862-0976 | |
| 39 | Novo Nordisk Investigational Site | Kushiro-shi, Hokkaido | Japan | 085-0032 | |
| 40 | Novo Nordisk Investigational Site | Kyoto-shi, Kyoto | Japan | 606-8507 | |
| 41 | Novo Nordisk Investigational Site | Minato-ku, Tokyo | Japan | 108-0075 | |
| 42 | Novo Nordisk Investigational Site | Mito-shi, Ibaraki | Japan | 310-0826 | |
| 43 | Novo Nordisk Investigational Site | Mito-shi, Ibaraki | Japan | 311-4153 | |
| 44 | Novo Nordisk Investigational Site | Miura-shi, Kanagawa | Japan | 238-0101 | |
| 45 | Novo Nordisk Investigational Site | Miyazaki | Japan | 880-0034 | |
| 46 | Novo Nordisk Investigational Site | Nagoya-shi, Aichi | Japan | 455-8530 | |
| 47 | Novo Nordisk Investigational Site | Nagoya-shi, Aichi | Japan | 456-0058 | |
| 48 | Novo Nordisk Investigational Site | Nishinomiya-shi, Hygo | Japan | 662 0971 | |
| 49 | Novo Nordisk Investigational Site | Obihiro-shi, Hokkaido | Japan | 080 0016 | |
| 50 | Novo Nordisk Investigational Site | Obihiro-shi, Hokkaido | Japan | 080 0848 | |
| 51 | Novo Nordisk Investigational Site | Oita-shi | Japan | 870 0039 | |
| 52 | Novo Nordisk Investigational Site | Okawa-shi, Fukuoka | Japan | 831-0016 | |
| 53 | Novo Nordisk Investigational Site | Onga-gun, Fukuoka | Japan | 811-4342 | |
| 54 | Novo Nordisk Investigational Site | Osaka-shi, Osaka | Japan | 530-0013 | |
| 55 | Novo Nordisk Investigational Site | Osaka-shi, Osaka | Japan | 533-0024 | |
| 56 | Novo Nordisk Investigational Site | Osaka-shi, Osaka | Japan | 536-0001 | |
| 57 | Novo Nordisk Investigational Site | Osaka | Japan | 569-1045 | |
| 58 | Novo Nordisk Investigational Site | Ota-ku, Tokyo | Japan | 1430015 | |
| 59 | Novo Nordisk Investigational Site | Saijo-shi, Ehime | Japan | 793-0027 | |
| 60 | Novo Nordisk Investigational Site | Sapporo-shi, Hokkaido | Japan | 004-0004 | |
| 61 | Novo Nordisk Investigational Site | Sapporo-shi, Hokkaido | Japan | 060-0001 | |
| 62 | Novo Nordisk Investigational Site | Sendai-shi, Miyagi | Japan | 980-0011 | |
| 63 | Novo Nordisk Investigational Site | Sendai-shi, Miyagi | Japan | 980-0021 | |
| 64 | Novo Nordisk Investigational Site | Shimotsuke-shi, Tochigi | Japan | 329-0433 | |
| 65 | Novo Nordisk Investigational Site | Shizuoka-shi, Shizuoka | Japan | 424-0853 | |
| 66 | Novo Nordisk Investigational Site | Tochigi | Japan | 323-0022 | |
| 67 | Novo Nordisk Investigational Site | Tokyo | Japan | 103-0027 | |
| 68 | Novo Nordisk Investigational Site | Tokyo | Japan | 103-0028 | |
| 69 | Novo Nordisk Investigational Site | Tokyo | Japan | 104-0031 | |
| 70 | Novo Nordisk Investigational Site | Tokyo | Japan | 169-0073 | |
| 71 | Novo Nordisk Investigational Site | Toshima-ku, Tokyo | Japan | 171-0021 | |
| 72 | Novo Nordisk Investigational Site | Toyonaka-shi, Osaka | Japan | 560-0082 | |
| 73 | Novo Nordisk Investigational Site | Ube-shi, Yamaguchi | Japan | 755-0046 | |
| 74 | Novo Nordisk Investigational Site | Urasoe-shi, | Japan | 901 2104 | |
| 75 | Novo Nordisk Investigational Site | Yamaguchi-shi, Yamaguchi | Japan | 754-0002 | |
| 76 | Novo Nordisk Investigational Site | Yamato-shi, Kanagawa | Japan | 242-0004 |
Sponsors and Collaborators
- Novo Nordisk A/S
Investigators
None specified.Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.Responsible Party:
Novo Nordisk A/S
ClinicalTrials.gov Identifier:
NCT02607306
Other Study ID Numbers:
- NN9068-4183
- U1111-1170-1332
- JapicCTI-153089
First Posted:
Nov 18, 2015
Last Update Posted:
Apr 9, 2021
Last Verified:
Mar 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | The trial was conducted at 71 sites in Japan. 71 sites screened and randomised subjects. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). 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). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. |
| Period Title: Overall Study | |||
| STARTED | 275 | 271 | 273 |
| COMPLETED | 254 | 248 | 263 |
| NOT COMPLETED | 21 | 23 | 10 |
Baseline Characteristics
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide | Total |
|---|---|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). 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). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Total of all reporting groups |
| Overall Participants | 275 | 271 | 273 | 819 |
| Age (Years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Years] |
56.9
(10.2)
|
57.8
(9.9)
|
56.8
(10.1)
|
57.2
(10.1)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
81
29.5%
|
76
28%
|
81
29.7%
|
238
29.1%
|
| Male |
194
70.5%
|
195
72%
|
192
70.3%
|
581
70.9%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||
| Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Not Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
275
100%
|
271
100%
|
273
100%
|
819
100%
|
| Race (NIH/OMB) (Count of Participants) | ||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
275
100%
|
271
100%
|
273
100%
|
819
100%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| White |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Glycosylated Haemoglobin (HbA1c) (Percentage of HbA1c) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [Percentage of HbA1c] |
8.52
(1.12)
|
8.53
(1.05)
|
8.32
(0.99)
|
8.45
(1.06)
|
Outcome Measures
| Title | Change From Baseline in HbA1c (Glycosylated Haemoglobin) Tested for Non-inferiority of IDegLira vs IDeg and Superiority of IDegLira vs Lira |
|---|---|
| Description | Change from baseline (week 0) in HbA1c after 52 weeks of treatment was measured. Statistical analyses were performed to test the hypotheses: non-inferiority of IDegLira vs. IDeg and superiority of IDegLira vs. Liraglutide (Lira). |
| Time Frame | Week 0, Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (819 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 | Liraglutide |
|---|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). 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). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. |
| Measure Participants | 275 | 271 | 273 |
| Mean (Standard Deviation) [Percentage of HbA1c] |
-2.42
(1.04)
|
-1.80
(1.02)
|
-1.80
(0.92)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Insulin Degludec/Liraglutide, Insulin Degludec |
|---|---|---|
| Comments | The change from baseline in response after 52 weeks are analysed using an ANCOVA model with treatment and pre-trial OAD as fixed factors and baseline HbA1c value as covariate. | |
| Type of Statistical Test | Non-Inferiority | |
| Comments | Non-inferiority of IDegLira vs. IDeg was confirmed if the 95% confidence interval for the mean treatment difference lies entirely below 0.3%. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | p-value for non-inferiority of IDegLira vs IDeg is presented | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Treatment contrast |
| Estimated Value | -0.63 | |
| Confidence Interval |
(2-Sided) 95% -0.75 to -0.52 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Insulin Degludec/Liraglutide, Liraglutide |
|---|---|---|
| Comments | The change from baseline in response after 52 weeks are analysed using an ANCOVA model with treatment and pre-trial OAD as fixed factors and baseline HbA1c value as covariate. | |
| Type of Statistical Test | Superiority | |
| Comments | Superiority of IDegLira vs. Lira was confirmed if the 95% confidence interval for the mean treatment difference for change from baseline in HbA1c lies entirely below 0.0%. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | p-value for superiority of IDegLira vs Lira is presented | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Treatment contrast |
| Estimated Value | -0.48 | |
| Confidence Interval |
(2-Sided) 95% -0.60 to -0.37 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in Body Weight (kg) |
|---|---|
| Description | Change from baseline (week 0) in body weight after 52 weeks of treatment. |
| Time Frame | Week 0, Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (819 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 | Liraglutide |
|---|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). 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). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. |
| Measure Participants | 275 | 271 | 273 |
| Mean (Standard Deviation) [Kg] |
2.9
(3.2)
|
4.1
(4.3)
|
-1.0
(3.4)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Insulin Degludec/Liraglutide, Insulin Degludec |
|---|---|---|
| Comments | The change from baseline in response after 52 weeks were analysed using an ANCOVA method with treatment and pre-trial OAD treatment as fixed factors and baseline body weight as covariate. | |
| Type of Statistical Test | Superiority | |
| Comments | A hierarchical testing procedure is used to control the overall type I error on a two sided 5% level. If and only if non-inferiority of IDegLira vs. IDeg and superiority of IDegLira vs. Lira are confirmed in the primary analysis (change in HbA1c), the three secondary confirmatory tests are performed for superiority of IDegLira versus IDeg with a fixed sequence (1. change in body weight, 2. number of treatment emergent severe or BG confirmed hypoglycaemic episodes and 3. change in HbA1c). | |
| Statistical Test of Hypothesis | p-Value | 0.0001 |
| Comments | p-value for superiority of IDegLira vs IDeg is presented | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Treatment contrast |
| Estimated Value | -1.19 | |
| Confidence Interval |
(2-Sided) 95% -1.80 to -0.59 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| 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 | Weeks 0-52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparator (819 subjects). Subjects in the safety set contributed to the evaluation "as treated". |
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). 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). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. |
| Measure Participants | 275 | 271 | 273 |
| Number [Episodes] |
467
|
869
|
13
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Insulin Degludec/Liraglutide, Insulin Degludec |
|---|---|---|
| Comments | The number of events is analysed using a negative binomial regression model (log link) with the logarithm of the treatment emergent exposure time (100 years) as offset. The model includes treatment and pre-trial OAD treatment as fixed factors. | |
| Type of Statistical Test | Superiority | |
| Comments | A hierarchical testing procedure is used to control the overall type I error on a two sided 5% level. If and only if non-inferiority of IDegLira vs. IDeg and superiority of IDegLira vs. Lira are confirmed in the primary analysis (change in HbA1c), the three secondary confirmatory tests are performed for superiority of IDegLira versus IDeg with a fixed sequence (1. change in body weight, 2. number of treatment emergent severe or BG confirmed hypoglycaemic episodes and 3. change in HbA1c). | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | p-value for superiority of IDegLira vs IDeg is presented | |
| Method | Negative binomial regression | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Treatment contrast |
| Estimated Value | 0.48 | |
| Confidence Interval |
(2-Sided) 95% 0.35 to 0.68 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in HbA1c (Glycosylated Haemoglobin) Tested for Superiority of IDegLira vs IDeg |
|---|---|
| Description | Change from baseline (week 0) in HbA1c after 52 weeks of treatment was measured. Statistical analysis was performed to test the hypothesis: superiority of IDegLira vs. IDeg. |
| Time Frame | Week 0, Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (819 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 | Liraglutide |
|---|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). 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). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. |
| Measure Participants | 275 | 271 | 273 |
| Mean (Standard Deviation) [Percentage of HbA1c] |
-2.42
(1.04)
|
-1.80
(1.02)
|
-1.80
(0.92)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Insulin Degludec/Liraglutide, Insulin Degludec |
|---|---|---|
| Comments | The change from baseline in response after 52 weeks are analysed using an ANCOVA model with treatment, pre-trial OAD as fixed factors and corresponding baseline HbA1c value as covariate. | |
| Type of Statistical Test | Superiority | |
| Comments | A hierarchical testing procedure is used to control the overall type I error on a two sided 5% level. If and only if non-inferiority of IDegLira vs. IDeg and superiority of IDegLira vs. Lira are confirmed in the primary analysis (change in HbA1c), the three secondary confirmatory tests are performed for superiority of IDegLira versus IDeg with a fixed sequence (1. change in body weight, 2. number of treatment emergent severe or BG confirmed hypoglycaemic episodes and 3. change in HbA1c). | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | p-value for superiority of IDegLira vs IDeg is presented | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Treatment contrast |
| Estimated Value | -0.63 | |
| Confidence Interval |
(2-Sided) 95% -0.75 to -0.52 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in Fasting Plasma Glucose (FPG) |
|---|---|
| Description | Change from baseline (week 0) in FPG after 52 weeks |
| Time Frame | Week 0, Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (819 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 | Liraglutide |
|---|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). 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). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. |
| Measure Participants | 275 | 271 | 272 |
| Mean (Standard Deviation) [mmol/L] |
-4.08
(2.47)
|
-3.97
(2.56)
|
-2.62
(1.95)
|
| Title | Insulin Dose |
|---|---|
| Description | Actual daily total insulin dose after 52 weeks of treatment. |
| Time Frame | After 52 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 (819 subjects). Subjects in the safety set contributed to the evaluation "as treated". Missing data were imputed using LOCF method. This endpoint evaluation is only applicable for subjects in IDegLira and IDeg arm. |
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec |
|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). 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). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. |
| Measure Participants | 275 | 271 |
| Mean (Standard Deviation) [Insulin Units/Day] |
27.7
(14.8)
|
34.8
(26.0)
|
| Title | Responder (Yes/no): HbA1c Less Than 7.0% |
|---|---|
| Description | Number of subjects with HbA1c less than 7.0% after 52 weeks of treatment. |
| Time Frame | After 52 weeks of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (819 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 | Liraglutide |
|---|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). 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). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. |
| Measure Participants | 275 | 271 | 273 |
| Yes |
245
89.1%
|
189
69.7%
|
208
76.2%
|
| No |
30
10.9%
|
82
30.3%
|
65
23.8%
|
| Title | Responder (Yes/no): HbA1c Less Than 7.0% and Change in Body Weight From Baseline Below or Equal to Zero |
|---|---|
| Description | Number of subjects with HbA1c less than 7.0% and without weight gain after 52 weeks of treatment. |
| Time Frame | After 52 weeks of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (819 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 | Liraglutide |
|---|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). 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). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. |
| Measure Participants | 275 | 271 | 273 |
| Yes |
44
16%
|
22
8.1%
|
142
52%
|
| No |
231
84%
|
249
91.9%
|
131
48%
|
| 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 52 weeks, who did not experience treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes during the last 12 weeks of treatment. Treatment emergent hypoglycaemic episode is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Severe or BG confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification or BG confirmed by a plasma glucose value < 3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. |
| Time Frame | After 52 weeks of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (819 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 | Liraglutide |
|---|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). 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). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. |
| Measure Participants | 270 | 265 | 271 |
| Yes |
227
82.5%
|
169
62.4%
|
206
75.5%
|
| No |
43
15.6%
|
96
35.4%
|
65
23.8%
|
| Title | Responder (Yes/no): HbA1c Less Than 7.0% and Change in Body Weight From Baseline Below or Equal to Zero and Without Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During the Last 12 Weeks of Treatment |
|---|---|
| Description | Number of subjects with HbA1c less than 7.0% and without weight gain, who did not experience treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes during the last 12 weeks of treatment. Treatment emergent hypoglycaemic episode is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Severe or BG confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification or BG confirmed by a plasma glucose value < 3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. |
| Time Frame | After 52 weeks of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (819 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 | Liraglutide |
|---|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). 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). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. |
| Measure Participants | 270 | 265 | 271 |
| Yes |
37
13.5%
|
22
8.1%
|
141
51.6%
|
| No |
233
84.7%
|
243
89.7%
|
130
47.6%
|
| Title | Responder (Yes/no): HbA1c Less Than 6.5% |
|---|---|
| Description | Number of subjects with HbA1c less than 6.5% after 52 weeks of treatment. |
| Time Frame | After 52 weeks of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (819 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 | Liraglutide |
|---|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). 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). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. |
| Measure Participants | 275 | 271 | 273 |
| Yes |
213
77.5%
|
134
49.4%
|
171
62.6%
|
| No |
62
22.5%
|
137
50.6%
|
102
37.4%
|
| Title | Responder (Yes/no): HbA1c Less Than 6.5% and Change in Body Weight From Baseline Below or Equal to Zero |
|---|---|
| Description | Number of subjects with HbA1c less than 6.5% and without weight gain after 52 weeks of treatment. |
| Time Frame | After 52 weeks of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (819 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 | Liraglutide |
|---|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). 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). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. |
| Measure Participants | 275 | 271 | 273 |
| Yes |
41
14.9%
|
17
6.3%
|
126
46.2%
|
| No |
234
85.1%
|
254
93.7%
|
147
53.8%
|
| Title | Responder (Yes/no): HbA1c Less Than 6.5% Without Treatment Emergent Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemic Episodes During the Last 12 Weeks of Treatment. |
|---|---|
| Description | Number of subjects with HbA1c less than 6.5% after 52 weeks, who did not experience treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes during the last 12 weeks of treatment. Treatment emergent hypoglycaemic episode is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Severe or BG confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification or BG confirmed by a plasma glucose value < 3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. |
| Time Frame | After 52 weeks of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (819 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 | Liraglutide |
|---|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). 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). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. |
| Measure Participants | 270 | 265 | 271 |
| Yes |
198
72%
|
123
45.4%
|
170
62.3%
|
| No |
72
26.2%
|
142
52.4%
|
101
37%
|
| Title | Responder (Yes/no): HbA1c Less Than 6.5% and Change in Body Weight From Baseline Below or Equal to Zero and Without Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During the Last 12 Weeks of Treatment |
|---|---|
| Description | Number of subjects with HbA1c less than 6.5% with no weight gain, who did not experience treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes during the last 12 weeks of treatment. Treatment emergent hypoglycaemic episode is defined as an event that had onset date on or after the first day of trial product administration, and no later than 7 days after the last day on trial product. Severe or BG confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification or BG confirmed by a plasma glucose value < 3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. |
| Time Frame | After 52 weeks of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (819 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 | Liraglutide |
|---|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). 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). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. |
| Measure Participants | 270 | 265 | 271 |
| Yes |
35
12.7%
|
17
6.3%
|
125
45.8%
|
| No |
235
85.5%
|
248
91.5%
|
146
53.5%
|
| Title | Change in Waist Circumference |
|---|---|
| Description | Change from baseline (week 0) in waist circumference after 52 weeks of treatment. |
| Time Frame | Week 0, Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (819 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 | Liraglutide |
|---|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). 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). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. |
| Measure Participants | 275 | 271 | 273 |
| Mean (Standard Deviation) [Cm] |
2.5
(4.5)
|
3.4
(5.2)
|
-1.1
(4.4)
|
| Title | Change in Blood Pressure (Systolic and Diastolic) |
|---|---|
| Description | Change from baseline in blood pressure (systolic and diastolic) after 52 weeks of treatment. |
| Time Frame | Week 0, Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (819 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 | Liraglutide |
|---|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). 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). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. |
| Measure Participants | 275 | 271 | 273 |
| Systolic blood pressure |
1.7
(12.0)
|
3.4
(14.3)
|
-1.8
(13.0)
|
| Diastolic blood pressure |
0.5
(7.9)
|
0.6
(9.3)
|
-0.4
(8.3)
|
| Title | Self-Measured Blood Glucose (SMBG) 9-point Profile: 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 52 weeks of the treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (819 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 | Liraglutide |
|---|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). 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). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. |
| Measure Participants | 275 | 271 | 273 |
| Before breakfast |
5.90
(1.45)
|
5.93
(1.64)
|
7.35
(1.70)
|
| 90 minutes after start of breakfast |
9.57
(2.83)
|
10.43
(3.16)
|
10.59
(3.25)
|
| Before lunch |
6.01
(1.90)
|
6.72
(2.59)
|
6.87
(2.07)
|
| 90 minutes after start of lunch |
9.85
(3.16)
|
11.12
(3.04)
|
10.59
(3.38)
|
| Before dinner |
6.47
(2.44)
|
6.90
(2.57)
|
7.03
(2.04)
|
| 90 minutes after start of dinner |
9.67
(3.01)
|
10.89
(3.25)
|
10.14
(3.03)
|
| Bedtime |
8.27
(2.79)
|
9.49
(3.28)
|
8.73
(2.58)
|
| At 4:00 a.m. |
6.12
(1.70)
|
6.41
(2.18)
|
7.27
(1.79)
|
| Before breakfast the following day |
5.77
(1.56)
|
5.71
(1.68)
|
7.13
(1.68)
|
| 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 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (819 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 | Liraglutide |
|---|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). 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). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. |
| Measure Participants | 275 | 269 | 272 |
| Mean (Standard Deviation) [mmol/L] |
-4.60
(2.65)
|
-3.84
(2.63)
|
-3.46
(2.37)
|
| Title | Change in SMBG 9-point Profile - Mean of Postprandial Increments (From Before Meal to 90 Min After for 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 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (819 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 | Liraglutide |
|---|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). 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). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. |
| Measure Participants | 275 | 269 | 272 |
| Mean (Standard Deviation) [mmol/L] |
-0.74
(2.51)
|
-0.27
(2.39)
|
-1.01
(2.38)
|
| Title | Total Cholesterol as a Ratio to Baseline at 52 Weeks |
|---|---|
| Description | Total cholesterol after 52 weeks of treatment was represented as ratio to baseline (week 0) values. |
| Time Frame | After 52 weeks of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (819 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 | Liraglutide |
|---|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). 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). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. |
| Measure Participants | 275 | 271 | 273 |
| Geometric Mean (Geometric Coefficient of Variation) [Ratio] |
0.92
(13.9)
|
0.97
(11.9)
|
0.94
(13.0)
|
| Title | Low Density Lipoprotein (LDL) Cholesterol as a Ratio to Baseline at 52 Weeks |
|---|---|
| Description | Low density lipoprotein (LDL) cholesterol after 52 weeks of treatment was represented as ratio to baseline (week 0) values. |
| Time Frame | After 52 weeks of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (819 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 | Liraglutide |
|---|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). 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). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. |
| Measure Participants | 275 | 271 | 273 |
| Geometric Mean (Geometric Coefficient of Variation) [Ratio] |
0.91
(23.4)
|
0.99
(18.2)
|
0.93
(24.2)
|
| Title | High Density Lipoprotein (HDL) Cholesterol as a Ratio to Baseline at 52 Weeks |
|---|---|
| Description | High density lipoprotein (HDL) cholesterol after 52 weeks of treatment was represented as ratio to baseline (week 0) values. |
| Time Frame | After 52 weeks of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (819 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 | Liraglutide |
|---|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). 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). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. |
| Measure Participants | 275 | 271 | 273 |
| Geometric Mean (Geometric Coefficient of Variation) [Ratio] |
0.94
(16.4)
|
0.94
(14.6)
|
0.99
(14.5)
|
| Title | Very Low Density Lipoprotein (VLDL) Cholesterol as a Ratio to Baseline at 52 Weeks |
|---|---|
| Description | Very low density lipoprotein (VLDL) cholesterol after 52 weeks of treatment was represented as ratio to baseline (week 0) values. |
| Time Frame | After 52 weeks of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (819 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 | Liraglutide |
|---|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). 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). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. |
| Measure Participants | 275 | 271 | 273 |
| Geometric Mean (Geometric Coefficient of Variation) [Ratio] |
0.92
(44.3)
|
0.97
(42.1)
|
0.91
(42.2)
|
| Title | Triglycerides as a Ratio to Baseline at 52 Weeks |
|---|---|
| Description | Triglycerides after 52 weeks of treatment was represented as ratio to baseline (week 0) values. |
| Time Frame | After 52 weeks of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (819 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 | Liraglutide |
|---|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). 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). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. |
| Measure Participants | 275 | 271 | 273 |
| Geometric Mean (Geometric Coefficient of Variation) [Ratio] |
0.91
(48.3)
|
0.96
(44.2)
|
0.91
(44.0)
|
| Title | Free Fatty Acids as a Ratio to Baseline at 52 Weeks |
|---|---|
| Description | Free fatty acids after 52 weeks of treatment was represented as ratio to baseline (week 0) values. |
| Time Frame | After 52 weeks of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (819 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 | Liraglutide |
|---|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). 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). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. |
| Measure Participants | 275 | 271 | 273 |
| Geometric Mean (Geometric Coefficient of Variation) [Ratio] |
0.74
(60.8)
|
0.70
(59.3)
|
0.93
(49.5)
|
| Title | Fasting C-peptide as a Ratio to Baseline at 52 Weeks |
|---|---|
| Description | Fasting C-peptide after 52 weeks of treatment was represented as ratio to baseline (week 0) values. |
| Time Frame | After 52 weeks of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (819 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 | Liraglutide |
|---|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). 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). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. |
| Measure Participants | 275 | 271 | 272 |
| Geometric Mean (Geometric Coefficient of Variation) [Ratio] |
0.61
(75.6)
|
0.42
(82.6)
|
1.12
(29.9)
|
| Title | Fasting Human Insulin as a Ratio to Baseline at 52 Weeks |
|---|---|
| Description | Fasting human insulin after 52 weeks of treatment was represented as ratio to baseline (week 0) values. |
| Time Frame | After 52 weeks of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (819 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 | Liraglutide |
|---|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). 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). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. |
| Measure Participants | 275 | 271 | 273 |
| Geometric Mean (Geometric Coefficient of Variation) [Ratio] |
0.90
(89.0)
|
0.61
(81.1)
|
1.52
(66.6)
|
| Title | Fasting Glucagon as a Ratio to Baseline at 52 Weeks |
|---|---|
| Description | Fasting glucagon after 52 weeks of treatment was represented as ratio to baseline (week 0) values. |
| Time Frame | After 52 weeks of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (819 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 | Liraglutide |
|---|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). 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). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. |
| Measure Participants | 275 | 271 | 272 |
| Geometric Mean (Geometric Coefficient of Variation) [Ratio] |
0.95
(27.9)
|
0.94
(27.6)
|
0.96
(25.7)
|
| Title | Proinsulin as a Ratio to Baseline at 52 Weeks |
|---|---|
| Description | Proinsulin after 52 weeks of treatment was represented as ratio to baseline (week 0) values. |
| Time Frame | After 52 weeks of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (819 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 | Liraglutide |
|---|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). 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). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. |
| Measure Participants | 270 | 266 | 264 |
| Geometric Mean (Geometric Coefficient of Variation) [Ratio] |
0.18
(231.5)
|
0.17
(188.8)
|
0.59
(85.9)
|
| Title | Number of Treatment Emergent Adverse Events (TEAEs) |
|---|---|
| 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 | 0-52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparator (819 subjects). Subjects in the safety set contributed to the evaluation "as treated". |
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). 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). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. |
| Measure Participants | 275 | 271 | 273 |
| Number [Events] |
873
|
829
|
885
|
| Title | Number of Treatment Emergent Severe or Blood Glucose (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 | 0-52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparator (819 subjects). Subjects in the safety set contributed to the evaluation "as treated". |
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). 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). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. |
| Measure Participants | 275 | 271 | 273 |
| Number [Episodes] |
135
|
362
|
136
|
| 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 | 0-52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparator (819 subjects). Subjects in the safety set contributed to the evaluation "as treated". |
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). 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). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. |
| Measure Participants | 275 | 271 | 273 |
| Number [Episodes] |
16
|
42
|
0
|
| 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 | 0-52 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparator (819 subjects). Subjects in the safety set contributed to the evaluation "as treated". |
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). 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). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. |
| Measure Participants | 275 | 271 | 273 |
| Number [Episodes] |
4830
|
6340
|
162
|
| Title | Anti-drug Antibodies: Anti-insulin Degludec Antibodies |
|---|---|
| Description | Insulin degludec (IDeg)-specific antibodies were measured at week 52, as %B/T (percentage of bound & precipitated radioactive drug/total added drug to the sample). A sample is measured in 2 different series. In series 1, the radioactive IDeg (tracer) and surplus unlabeled IDeg are added to the sample. In series 2, the tracer and surplus unlabeled human insulin are added to the sample. Series 1 represents unspecific background binding. Series 2 represents IDeg specific antibodies including unspecific background binding. The reported %B/T is calculated by subtracting the background %B/T in series 1 from the %B/T result in series 2. If the background result has higher values than the %B/T in series 2, the resulting value is negative %B/T. Here, a negative %B/T value means that the test samples do not have IDeg-specific antibodies. The reason for getting a negative value for %B/T is due to variation in the analytical background. Thus, the results presented are not a change from baseline. |
| Time Frame | at week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparator (819 subjects). Subjects in the safety set contributed to the evaluation "as treated". Missing data were imputed using LOCF method. This endpoint is only applicable for subjects in IDegLira and IDeg arm. |
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec |
|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). 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). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. |
| Measure Participants | 275 | 271 |
| Mean (Standard Deviation) [Percentage B/T] |
0.12
(3.34)
|
-0.11
(0.42)
|
| Title | Anti-drug Antibodies: Number of Participants Positive or Negative for Anti-liraglutide Antibodies |
|---|---|
| Description | Anti-liraglutide antibodies were measured at week 52. Number of participants positive or negative for anti-liraglutide antibodies at week 52 were reported. |
| Time Frame | at week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparator (819 subjects). Subjects in the safety set contributed to the evaluation "as treated". Missing data were imputed using LOCF method.This endpoint is only applicable for subjects in IDegLira and Lira arm. |
| Arm/Group Title | Insulin Degludec/Liraglutide | Liraglutide |
|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). 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). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. |
| Measure Participants | 275 | 273 |
| Negative |
247
89.8%
|
224
82.7%
|
| Positive |
28
10.2%
|
49
18.1%
|
| 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 52. |
| Time Frame | at screening (week -2 to week 0), at week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparator (819 subjects). Subjects in the safety set contributed to the evaluation "as treated". Number Analyzed = subjects with available data. |
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). 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). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. |
| Measure Participants | 275 | 271 | 273 |
| Left eye - at screening visit - normal |
225
81.8%
|
213
78.6%
|
211
77.3%
|
| Left eye - at screening visit - Abn, NCS |
10
3.6%
|
16
5.9%
|
14
5.1%
|
| Left eye - at screening visit - Abn, CS |
39
14.2%
|
42
15.5%
|
47
17.2%
|
| Left eye - week 52 - normal |
217
78.9%
|
214
79%
|
212
77.7%
|
| Left eye - week 52 - Abn, NCS |
17
6.2%
|
16
5.9%
|
15
5.5%
|
| Left eye - week 52 - Abn, CS |
40
14.5%
|
41
15.1%
|
45
16.5%
|
| Right eye - at screening visit - normal |
224
81.5%
|
212
78.2%
|
207
75.8%
|
| Right eye - at screening visit - Abn, NCS |
10
3.6%
|
14
5.2%
|
12
4.4%
|
| Right eye - at screening visit - Abn, CS |
41
14.9%
|
45
16.6%
|
54
19.8%
|
| Right eye - week 52 - normal |
220
80%
|
217
80.1%
|
209
76.6%
|
| Right eye - week 52 - Abn, NCS |
14
5.1%
|
14
5.2%
|
15
5.5%
|
| Right eye - week 52 - Abn, CS |
41
14.9%
|
40
14.8%
|
49
17.9%
|
| 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 52. |
| Time Frame | at screening (week -2 to week 0), at week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparator (819 subjects). Subjects in the safety set contributed to the evaluation "as treated". |
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). 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). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. |
| Measure Participants | 275 | 271 | 273 |
| At screening visit - normal |
228
82.9%
|
230
84.9%
|
222
81.3%
|
| At screening visit - Abn, NCS |
40
14.5%
|
38
14%
|
41
15%
|
| At screening visit - Abn, CS |
7
2.5%
|
3
1.1%
|
10
3.7%
|
| Week 52 - normal |
238
86.5%
|
232
85.6%
|
233
85.3%
|
| Week 52 - Abn, NCS |
30
10.9%
|
35
12.9%
|
34
12.5%
|
| Week 52 - Abn, CS |
7
2.5%
|
4
1.5%
|
6
2.2%
|
| Title | Change in Clinical Evaluation: Pulse |
|---|---|
| Description | Change in pulse after 52 weeks of treatment. |
| Time Frame | Week 0, week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set (SAS) included all subjects receiving at least one dose of the investigational product or comparator (819 subjects). Subjects in the safety set contributed to the evaluation "as treated". |
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide |
|---|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). 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). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. |
| Measure Participants | 275 | 271 | 273 |
| Mean (Standard Deviation) [beats per minute] |
3.9
(9.5)
|
0.8
(8.9)
|
4.2
(9.1)
|
| Title | Serum Concentrations of Insulin Degludec |
|---|---|
| Description | Samples from the IDegLira and IDeg arms were analysed for serum concentrations of insulin degludec using validated ELISA assays. |
| Time Frame | Weeks 2, 8, 16, 26, 44, 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (819 subjects). All subjects in FAS with at least one valid concentration value were included in the analysis. No imputations of missing concentration values were applied. Number Analyzed = subjects with available data. This endpoint is only applicable for subjects in IDegLira and IDeg arm. |
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec |
|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). 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). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. |
| Measure Participants | 275 | 271 |
| At week 2 |
1468.7
(55.9)
|
1477.1
(61.3)
|
| At week 8 |
2246.0
(72.2)
|
2524.6
(71.5)
|
| At week 16 |
2511.0
(83.6)
|
2856.4
(84.4)
|
| At week 26 |
2597.3
(88.3)
|
2946.9
(91.1)
|
| At week 44 |
2766.6
(85.8)
|
3238.8
(91.7)
|
| At week 52 |
2393.8
(116.7)
|
3124.4
(101.2)
|
| Title | Plasma Concentrations of Liraglutide |
|---|---|
| Description | Samples from the IDegLira and liraglutide arms were assayed for plasma concentrations of liraglutide using validated ELISA assays. |
| Time Frame | Weeks 2, 8, 16, 26, 44, 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) included all randomised subjects (819 subjects). All subjects in FAS with at least one valid concentration value were included in the analysis. No imputations of missing concentration values were applied. Number Analyzed = subjects with available data. This endpoint is only applicable for subjects in IDegLira and Lira arm. |
| Arm/Group Title | Insulin Degludec/Liraglutide | Liraglutide |
|---|---|---|
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). 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). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. |
| Measure Participants | 275 | 273 |
| At week 2 |
5681.3
(49.4)
|
6081.6
(65.4)
|
| At week 8 |
9107.8
(61.4)
|
14539.5
(71.0)
|
| At week 16 |
10038.1
(69.5)
|
14046.5
(73.0)
|
| At week 26 |
9995.3
(77.5)
|
13904.2
(91.8)
|
| At week 44 |
8791.7
(81.0)
|
12855.6
(112.7)
|
| At week 52 |
7426.2
(103.5)
|
12127.4
(142.4)
|
Adverse Events
| Time Frame | Week 0 (randomisation) to week 52 (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. | |||||
| Arm/Group Title | Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide | |||
| Arm/Group Description | Eligible subjects were treated with insulin degludec/liraglutide (IDegLira) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency; dose reduction was allowed in case of safety concern). The recommended starting dose of IDegLira was 10 dose steps (10 units IDeg/0.36 mg liraglutide). 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). One follow-up visit was scheduled 7 days after end of treatment. IDegLira was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with insulin degludec (IDeg) once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). The recommended starting dose of IDeg was 10 units. IDeg was titrated twice weekly according to a predefined titration algorithm, aiming to reach a fasting plasma glucose target between 72 mg/dL (4.0 mmol/L) and 90 mg/dL (5.0 mmol/L). There was no maximum dose decided for IDeg. One follow-up visit was scheduled 7 days after end of treatment. IDeg was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | Eligible subjects were treated with liraglutide once daily (OD) in combination with pre-trial oral anti diabetic drugs (at stable dose level and dosing frequency unless there were safety concerns, in which case dose reduction was allowed). For liraglutide the starting dose of liraglutide was 0.3 mg/day and subsequent weekly dose escalation by 0.3 mg weekly to a fixed maximum dose of 1.8 mg/day. One follow-up visit was scheduled 7 days after end of treatment. Liraglutide was injected subcutaneously in the thigh, upper arm (deltoid region) or abdomen. The injection area chosen remained unchanged throughout the trial, although rotation within the area was recommended. | |||
All Cause Mortality |
||||||
| Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/275 (0.4%) | 0/271 (0%) | 0/273 (0%) | |||
Serious Adverse Events |
||||||
| Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 17/275 (6.2%) | 13/271 (4.8%) | 14/273 (5.1%) | |||
| Cardiac disorders | ||||||
| Acute myocardial infarction | 0/275 (0%) | 0 | 1/271 (0.4%) | 1 | 0/273 (0%) | 0 |
| Angina pectoris | 2/275 (0.7%) | 2 | 0/271 (0%) | 0 | 0/273 (0%) | 0 |
| Atrioventricular block complete | 0/275 (0%) | 0 | 1/271 (0.4%) | 1 | 0/273 (0%) | 0 |
| Cardiac disorder | 1/275 (0.4%) | 1 | 0/271 (0%) | 0 | 0/273 (0%) | 0 |
| Myocardial ischaemia | 0/275 (0%) | 0 | 1/271 (0.4%) | 1 | 0/273 (0%) | 0 |
| Sinus node dysfunction | 0/275 (0%) | 0 | 0/271 (0%) | 0 | 1/273 (0.4%) | 1 |
| Eye disorders | ||||||
| Retinal detachment | 1/275 (0.4%) | 1 | 0/271 (0%) | 0 | 0/273 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| Autoimmune pancreatitis | 0/275 (0%) | 0 | 0/271 (0%) | 0 | 1/273 (0.4%) | 1 |
| Gastrooesophageal reflux disease | 1/275 (0.4%) | 1 | 0/271 (0%) | 0 | 0/273 (0%) | 0 |
| Large intestine polyp | 1/275 (0.4%) | 1 | 0/271 (0%) | 0 | 0/273 (0%) | 0 |
| Pancreatitis acute | 1/275 (0.4%) | 1 | 0/271 (0%) | 0 | 0/273 (0%) | 0 |
| General disorders | ||||||
| Chills | 0/275 (0%) | 0 | 0/271 (0%) | 0 | 1/273 (0.4%) | 1 |
| Hepatobiliary disorders | ||||||
| Cholecystitis | 1/275 (0.4%) | 1 | 0/271 (0%) | 0 | 0/273 (0%) | 0 |
| Cholecystitis acute | 0/275 (0%) | 0 | 0/271 (0%) | 0 | 1/273 (0.4%) | 1 |
| Infections and infestations | ||||||
| Cellulitis | 0/275 (0%) | 0 | 0/271 (0%) | 0 | 1/273 (0.4%) | 1 |
| Herpes zoster meningitis | 0/275 (0%) | 0 | 1/271 (0.4%) | 1 | 0/273 (0%) | 0 |
| Pneumonia | 0/275 (0%) | 0 | 0/271 (0%) | 0 | 1/273 (0.4%) | 1 |
| Pneumonia haemophilus | 1/275 (0.4%) | 1 | 0/271 (0%) | 0 | 0/273 (0%) | 0 |
| Tonsillitis | 0/275 (0%) | 0 | 1/271 (0.4%) | 1 | 0/273 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||
| Femoral neck fracture | 0/275 (0%) | 0 | 0/271 (0%) | 0 | 1/273 (0.4%) | 1 |
| Meniscus injury | 1/275 (0.4%) | 1 | 0/271 (0%) | 0 | 0/273 (0%) | 0 |
| Spinal compression fracture | 1/275 (0.4%) | 1 | 0/271 (0%) | 0 | 0/273 (0%) | 0 |
| Thoracic vertebral fracture | 1/275 (0.4%) | 1 | 0/271 (0%) | 0 | 0/273 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||
| Hypoglycaemia | 1/275 (0.4%) | 1 | 0/271 (0%) | 0 | 0/273 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Adrenal neoplasm | 0/275 (0%) | 0 | 1/271 (0.4%) | 1 | 0/273 (0%) | 0 |
| Benign neoplasm of bladder | 1/275 (0.4%) | 1 | 0/271 (0%) | 0 | 0/273 (0%) | 0 |
| Breast cancer | 0/275 (0%) | 0 | 0/271 (0%) | 0 | 1/273 (0.4%) | 1 |
| Gastric cancer stage I | 1/275 (0.4%) | 1 | 0/271 (0%) | 0 | 0/273 (0%) | 0 |
| Lung adenocarcinoma | 0/275 (0%) | 0 | 1/271 (0.4%) | 1 | 0/273 (0%) | 0 |
| Lung neoplasm malignant | 0/275 (0%) | 0 | 1/271 (0.4%) | 1 | 0/273 (0%) | 0 |
| Metastases to lymph nodes | 0/275 (0%) | 0 | 1/271 (0.4%) | 1 | 0/273 (0%) | 0 |
| Nervous system disorders | ||||||
| Carpal tunnel syndrome | 0/275 (0%) | 0 | 1/271 (0.4%) | 1 | 0/273 (0%) | 0 |
| Cerebral infarction | 1/275 (0.4%) | 1 | 0/271 (0%) | 0 | 0/273 (0%) | 0 |
| Facial paralysis | 0/275 (0%) | 0 | 0/271 (0%) | 0 | 1/273 (0.4%) | 1 |
| Hypoglycaemic unconsciousness | 0/275 (0%) | 0 | 1/271 (0.4%) | 1 | 0/273 (0%) | 0 |
| Thalamic infarction | 1/275 (0.4%) | 1 | 0/271 (0%) | 0 | 0/273 (0%) | 0 |
| Thrombotic cerebral infarction | 0/275 (0%) | 0 | 1/271 (0.4%) | 1 | 0/273 (0%) | 0 |
| Psychiatric disorders | ||||||
| Suicide attempt | 0/275 (0%) | 0 | 0/271 (0%) | 0 | 1/273 (0.4%) | 1 |
| Reproductive system and breast disorders | ||||||
| Endometrial hyperplasia | 0/275 (0%) | 0 | 1/271 (0.4%) | 1 | 0/273 (0%) | 0 |
| Uterine prolapse | 0/275 (0%) | 0 | 0/271 (0%) | 0 | 1/273 (0.4%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Sleep apnoea syndrome | 1/275 (0.4%) | 1 | 1/271 (0.4%) | 1 | 1/273 (0.4%) | 1 |
| Surgical and medical procedures | ||||||
| Cardiac ablation | 0/275 (0%) | 0 | 0/271 (0%) | 0 | 1/273 (0.4%) | 1 |
| Large intestinal polypectomy | 0/275 (0%) | 0 | 0/271 (0%) | 0 | 1/273 (0.4%) | 1 |
| Vascular disorders | ||||||
| Peripheral arterial occlusive disease | 0/275 (0%) | 0 | 1/271 (0.4%) | 1 | 0/273 (0%) | 0 |
| Varicose vein | 0/275 (0%) | 0 | 1/271 (0.4%) | 1 | 0/273 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||
| Insulin Degludec/Liraglutide | Insulin Degludec | Liraglutide | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 153/275 (55.6%) | 137/271 (50.6%) | 158/273 (57.9%) | |||
| Eye disorders | ||||||
| Diabetic retinopathy | 17/275 (6.2%) | 17 | 12/271 (4.4%) | 14 | 11/273 (4%) | 11 |
| Gastrointestinal disorders | ||||||
| Constipation | 27/275 (9.8%) | 28 | 12/271 (4.4%) | 12 | 38/273 (13.9%) | 42 |
| Diarrhoea | 15/275 (5.5%) | 20 | 12/271 (4.4%) | 14 | 24/273 (8.8%) | 31 |
| Nausea | 9/275 (3.3%) | 13 | 5/271 (1.8%) | 7 | 23/273 (8.4%) | 30 |
| Infections and infestations | ||||||
| Influenza | 15/275 (5.5%) | 15 | 9/271 (3.3%) | 9 | 9/273 (3.3%) | 9 |
| Pharyngitis | 11/275 (4%) | 13 | 15/271 (5.5%) | 18 | 9/273 (3.3%) | 9 |
| Viral upper respiratory tract infection | 106/275 (38.5%) | 166 | 91/271 (33.6%) | 161 | 94/273 (34.4%) | 155 |
| Investigations | ||||||
| Lipase increased | 6/275 (2.2%) | 8 | 0/271 (0%) | 0 | 15/273 (5.5%) | 15 |
| Weight increased | 4/275 (1.5%) | 4 | 19/271 (7%) | 19 | 1/273 (0.4%) | 1 |
| Nervous system disorders | ||||||
| Headache | 7/275 (2.5%) | 11 | 7/271 (2.6%) | 12 | 15/273 (5.5%) | 17 |
| Skin and subcutaneous tissue disorders | ||||||
| Eczema | 16/275 (5.8%) | 18 | 6/271 (2.2%) | 6 | 9/273 (3.3%) | 10 |
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:
NCT02607306
Other Study ID Numbers:
- NN9068-4183
- U1111-1170-1332
- JapicCTI-153089
First Posted:
Nov 18, 2015
Last Update Posted:
Apr 9, 2021
Last Verified:
Mar 1, 2021