Diabetes, Diabetes Mellitus, Type 2
Conditions
Brief summary
This trial is conducted in Asia, Europe and the United States of America (USA). The aim of this trial is to compare the efficacy and safety of insulin degludec/liraglutide (IDegLira) and insulin degludec (IDeg) in subjects with type 2 diabetes. Subjects continue their pre-trial treatment with metformin throughout the entire trial.
Interventions
DRUGinsulin degludec/liraglutide
IDeg/Lira treatment will be initiated and titrated (individually adjusted) twice weekly according to the mean self measured plasma glucose (SMPG) (fasting). IDegLira is injected subcutaneously (under the skin) once daily.
DRUGinsulin degludec
IDeg treatment will be initiated and titrated (individually adjusted) twice weekly according to the mean self measured plasma glucose (SMPG) (fasting). IDeg is injected subcutaneously (under the skin) once daily.
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects with type 2 diabetes * HbA1c (glycosylated haemoglobin) 7.5-10.0% (both inclusive) * Subjects on stable daily doses for at least 90 days prior to trial start of: Basal insulin (total daily basal insulin dose within the range of 20-40U in combination with: metformin (1500 mg or more or max. tolerated dose) or metformin (1500 mg or more or max. tolerated dose) and SU (sulfonylurea) (equal to or more than half of the max. approved dose according to local label) or metformin and glinides (equal to or more than half of the max. approved dose according to local label) * BMI (Body Mass Index) more than or equal to 27 kg/m\^2
Exclusion criteria
* Treatment with glucagon like peptide-1 (GLP-1) receptor agonists (e.g. exenatide, liraglutide), dipeptidyl peptidase 4 (DPP-4) inhibitors and/or thiazolidinediones within 90 days prior to trial start * Impaired liver function * Impaired renal function * Screening calcitonin equal to or above 50 ng/l * Subjects with personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN 2) * Cardiac disorder defined as: congestive heart failure (NYHA class III-IV), diagnosis of unstable angina pectoris, cerebral stroke and/or myocardial infarction within the last 52 weeks prior to trial start and/or planned coronary, carotid or peripheral artery revascularisation procedures * Severe uncontrolled treated or untreated hypertension (systolic blood pressure equal to or above 180 mm Hg or diastolic blood pressure equal to or above 100 mm Hg) * Acute treatment required proliferative retinopathy or maculopathy (macular oedema) according to physician's opinion * History of chronic pancreatitis or idiopathic acute pancreatitis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HbA1c (Glycosylated Haemoglobin) | Week 0, week 26 | Observed mean change from baseline in HbA1c after 26 Weeks of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Body Weight | Week 0, week 26 | Observed mean change from baseline in body weight after 26 Weeks of treatment. |
Countries
Bulgaria, Denmark, Hungary, India, Slovenia, Switzerland, United States
Participant flow
Recruitment details
The trial was conducted at 75 sites in 7 countries: Bulgaria (6), Switzerland (2), Denmark (3), Hungary (3), India (6), Slovenia (3), and the United States (52).
Participants by arm
| Arm | Count |
|---|---|
| IDegLira IDegLira was injected subcutaneously (under the skin) once daily for 26 weeks in combination with metformin treatment. Metformin dose was maintained at the stable, pre-randomisation dose and frequency level. Treatment with IDegLira was initiated at 16 dose steps containing 16 units insulin degludec and 0.6 mg liraglutide. Dose adjustment of IDegLira was to be performed twice weekly based on the mean of three pre-breakfast SMPG values measured on the day of titration and the two days prior to titration aiming at a fasting glycaemic target of 4.0-5.0 mmol/L. | 199 |
| IDeg Insulin degludec (IDeg) was injected subcutaneously (under the skin) once daily for 26 weeks. Metformin dose was maintained at the stable, pre-randomisation dose and frequency level. Treatment with IDeg was initiated with 16 units. Dose adjustment of IDeg was to be performed twice weekly based on the mean of 3 preceding daily fasting SMPG values on 3 consecutive days (fasting glycaemic target of 4.0-5.0 mmol/L). | 199 |
| Total | 398 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 3 |
| Overall Study | Lack of Efficacy | 1 | 2 |
| Overall Study | Protocol Violation | 0 | 2 |
| Overall Study | Site closure | 8 | 7 |
| Overall Study | Unclassified | 9 | 6 |
| Overall Study | Withdrawal Criteria | 13 | 15 |
Baseline characteristics
| Characteristic | IDegLira | IDeg | Total |
|---|---|---|---|
| Age, Continuous | 56.8 years STANDARD_DEVIATION 8.9 | 57.5 years STANDARD_DEVIATION 10.5 | 57.2 years STANDARD_DEVIATION 9.7 |
| Body Weight | 95.4 kg STANDARD_DEVIATION 19.4 | 93.5 kg STANDARD_DEVIATION 20 | 94.5 kg STANDARD_DEVIATION 19.7 |
| HbA1c (glycosylated haemoglobin) | 8.7 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.7 | 8.8 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.7 | 8.8 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.7 |
| Sex: Female, Male Female | 87 Participants | 93 Participants | 180 Participants |
| Sex: Female, Male Male | 112 Participants | 106 Participants | 218 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 45 / 199 | 29 / 199 |
| serious Total, serious adverse events | 7 / 199 | 11 / 199 |
Outcome results
Primary
Change From Baseline in HbA1c (Glycosylated Haemoglobin)
Observed mean change from baseline in HbA1c after 26 Weeks of treatment.
Time frame: Week 0, week 26
Population: Full analysis set. Missing data was imputed using last observation carried forward (LOCF).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IDegLira | Change From Baseline in HbA1c (Glycosylated Haemoglobin) | -1.90 percentage of glycosylated haemoglobin | Standard Deviation 1.09 |
| IDeg | Change From Baseline in HbA1c (Glycosylated Haemoglobin) | -0.89 percentage of glycosylated haemoglobin | Standard Deviation 1.18 |
p-value: <0.000195% CI: [-1.25, -0.84]ANCOVA
Secondary
Change in Body Weight
Observed mean change from baseline in body weight after 26 Weeks of treatment.
Time frame: Week 0, week 26
Population: Full analysis set. Missing data was imputed using LOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IDegLira | Change in Body Weight | -2.7 kg | Standard Deviation 3.7 |
| IDeg | Change in Body Weight | 0.0 kg | Standard Deviation 3.4 |