Phase 3
Completed N=819
A Trial Comparing the Efficacy and Safety of Insulin Degludec/Liraglutide, Insulin Degludec and Liraglutide in Japanese Subjects With Type 2 Diabetes Mellitus.
Source: ClinicalTrials.gov NCT02607306 ↗Enrolled (actual)
819
Serious AEs
5.4%
Results posted
Jul 2019
Primary outcomePrimary: Change From Baseline in HbA1c (Glycosylated Haemoglobin) Tested for Non-inferiority of IDegLira vs IDeg and Superiority of IDegLira vs Lira — -2.42; -1.80; -1.80 Percentage of HbA1c — p=<0.0001
◆ Published Evidence
Established
24citations · ~3 / year
Superior efficacy with a fixed-ratio combination of insulin degludec and liraglutide (IDegLira) compared with insulin degludec and liraglutide in insulin-naïve Japanese patients with type 2 diabetes in a phase 3, open-label, randomized trial.
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.
Linked Publications (2)
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Superior efficacy with a fixed-ratio combination of insulin degludec and liraglutide (IDegLira) compared with insulin degludec and liraglutide in insulin-naïve Japanese patients with type 2 diabetes in a phase 3, open-label, randomized trial.
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Efficacy and safety of the fixed-ratio combination of insulin degludec and liraglutide by baseline glycated hemoglobin, body mass index and age in Japanese individuals with type 2 diabetes: A subgroup analysis of two phase III trials.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in HbA1c (Glycosylated Haemoglobin) Tested for Non-inferiority of IDegLira vs IDeg and Superiority of IDegLira vs Lira |
-2.42; -1.80; -1.80 | <0.0001 sig |
| SECONDARY Change From Baseline in Body Weight (kg) |
2.9; 4.1; -1.0 | 0.0001 sig |
| SECONDARY Number of Treatment Emergent Severe or Blood Glucose (BG) Confirmed Hypoglycaemic Episodes |
467; 869; 13 | <0.0001 sig |
| SECONDARY Change From Baseline in HbA1c (Glycosylated Haemoglobin) Tested for Superiority of IDegLira vs IDeg |
-2.42; -1.80; -1.80 | <0.0001 sig |
| SECONDARY Change From Baseline in Fasting Plasma Glucose (FPG) |
-4.08; -3.97; -2.62 | — |
| SECONDARY Insulin Dose |
27.7; 34.8 | — |
| SECONDARY Responder (Yes/no): HbA1c Less Than 7.0% |
245; 189; 208; 30; 82; 65 | — |
| SECONDARY Responder (Yes/no): HbA1c Less Than 7.0% and Change in Body Weight From Baseline Below or Equal to Zero |
44; 22; 142; 231; 249; 131 | — |
| SECONDARY 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. |
227; 169; 206; 43; 96; 65 | — |
| SECONDARY 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 |
37; 22; 141; 233; 243; 130 | — |
| SECONDARY Responder (Yes/no): HbA1c Less Than 6.5% |
213; 134; 171; 62; 137; 102 | — |
| SECONDARY Responder (Yes/no): HbA1c Less Than 6.5% and Change in Body Weight From Baseline Below or Equal to Zero |
41; 17; 126; 234; 254; 147 | — |
| SECONDARY 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. |
198; 123; 170; 72; 142; 101 | — |
| SECONDARY 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 |
35; 17; 125; 235; 248; 146 | — |
| SECONDARY Change in Waist Circumference |
2.5; 3.4; -1.1 | — |
| SECONDARY Change in Blood Pressure (Systolic and Diastolic) |
1.7; 3.4; -1.8; 0.5; 0.6; -0.4 | — |
| SECONDARY Self-Measured Blood Glucose (SMBG) 9-point Profile: 9-point Profile (Individual Points in the Profile) |
5.90; 5.93; 7.35; 9.57; 10.43; 10.59 | — |
| SECONDARY Change in SMBG 9-point Profile - Mean of the 9-point Profile |
-4.60; -3.84; -3.46 | — |
| SECONDARY Change in SMBG 9-point Profile - Mean of Postprandial Increments (From Before Meal to 90 Min After for Breakfast, Lunch and Dinner) |
-0.74; -0.27; -1.01 | — |
| SECONDARY Total Cholesterol as a Ratio to Baseline at 52 Weeks |
0.92; 0.97; 0.94 | — |
| SECONDARY Low Density Lipoprotein (LDL) Cholesterol as a Ratio to Baseline at 52 Weeks |
0.91; 0.99; 0.93 | — |
| SECONDARY High Density Lipoprotein (HDL) Cholesterol as a Ratio to Baseline at 52 Weeks |
0.94; 0.94; 0.99 | — |
| SECONDARY Very Low Density Lipoprotein (VLDL) Cholesterol as a Ratio to Baseline at 52 Weeks |
0.92; 0.97; 0.91 | — |
| SECONDARY Triglycerides as a Ratio to Baseline at 52 Weeks |
0.91; 0.96; 0.91 | — |
| SECONDARY Free Fatty Acids as a Ratio to Baseline at 52 Weeks |
0.74; 0.70; 0.93 | — |
| SECONDARY Fasting C-peptide as a Ratio to Baseline at 52 Weeks |
0.61; 0.42; 1.12 | — |
| SECONDARY Fasting Human Insulin as a Ratio to Baseline at 52 Weeks |
0.90; 0.61; 1.52 | — |
| SECONDARY Fasting Glucagon as a Ratio to Baseline at 52 Weeks |
0.95; 0.94; 0.96 | — |
| SECONDARY Proinsulin as a Ratio to Baseline at 52 Weeks |
0.18; 0.17; 0.59 | — |
| SECONDARY Number of Treatment Emergent Adverse Events (TEAEs) |
873; 829; 885 | — |
| SECONDARY Number of Treatment Emergent Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemic Episodes |
135; 362; 136 | — |
| SECONDARY Number of Treatment Emergent Nocturnal Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes |
16; 42; 0 | — |
| SECONDARY Number of Treatment Emergent Hypoglycaemic Episodes According to American Diabetes Association (ADA) Definition |
4830; 6340; 162 | — |
| SECONDARY Anti-drug Antibodies: Anti-insulin Degludec Antibodies |
0.12; -0.11 | — |
| SECONDARY Anti-drug Antibodies: Number of Participants Positive or Negative for Anti-liraglutide Antibodies |
247; 224; 28; 49 | — |
| SECONDARY Change in Clinical Evaluation: Fundoscopy or Fundus Photography |
225; 213; 211; 10; 16; 14 | — |
| SECONDARY Change in Clinical Evaluation: Electrocardiogram (ECG) |
228; 230; 222; 40; 38; 41 | — |
| SECONDARY Change in Clinical Evaluation: Pulse |
3.9; 0.8; 4.2 | — |
| SECONDARY Serum Concentrations of Insulin Degludec |
1468.7; 1477.1; 2246.0; 2524.6; 2511.0; 2856.4 | — |
| SECONDARY Plasma Concentrations of Liraglutide |
5681.3; 6081.6; 9107.8; 14539.5; 10038.1; 14046.5 | — |
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT02607306) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.