Diabetes, Diabetes Mellitus, Type 2
Conditions
Brief summary
This trial was conducted in Europe and North America. The aim of this clinical trial was to compare NN1250 (insulin degludec (IDeg)), a soluble insulin basal analogue (SIBA), with insulin glargine (IGlar), as add-on to subject's ongoing treatment with metformin and/or DPP-4 (dipeptyl peptidase 4) inhibitors, in patients with type 2 diabetes being treated with oral anti-diabetic drugs (OADs).
Interventions
DRUGinsulin degludec
Will be injected subcutaneously (under the skin) once daily three times weekly.
DRUGinsulin glargine
Will be injected subcutaneously (under the skin) once daily administered at the same time each day.
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Type 2 diabetes (diagnosed clinically) for at least 6 months * Insulin naïve subjects (allowed are: previous short term insulin treatment up to 14 days; treatment during hospitalisation or during gestational diabetes is allowed for periods longer than 14 days) * Current treatment: metformin monotherapy or metformin in any combination with insulin secretagogues (sulphonylurea (SU) or glinide), DPP-4 inhibitor, alpha-glucosidase-inhibitor (acarbose) with unchanged dosing for at least 3 months prior to visit 1 with the minimum doses stated: -Metformin: alone or in combination (including fixed combination) 1500 mg daily or maximum tolerated dose (at least 1000 mg daily)-Insulin secretagogue (sulfonylurea (SU) or glinide): minimum half of the daily maximal dose according to local labelling -DPP-4 inhibitor: minimum half of the daily maximal dose according to local labelling -alpha-glucosidase-inhibitor (acarbose): minimum half of the daily maximal dose or maximum tolerated dose * HbA1c 7.0-10.0 % (both inclusive) by central laboratory analysis * BMI (Body Mass Index) below or equal to 45.0 kg/m\^2
Exclusion criteria
* Use within the last 3 months prior to Visit 1 of: Thiazoledinediones (TZDs), Exenatide or Liraglutide * Cardiovascular disease, within the last 6 months prior to visit 1, defined as: stroke; decompensated heart failure New York Heart Association (NYHA) class III or IV; myocardial infarction; unstable angina pectoris; or coronary arterial bypass graft or angioplasty * Uncontrolled treated/untreated severe hypertension (systolic blood pressure at least 180 millimetre (mm) mercury (Hg) and/or diastolic blood pressure at least 100 mmHg) * Pregnancy, breast-feeding, the intention of becoming pregnant or not using adequate contraceptive measures according to local requirements * Cancer and medical history of cancer hereof (except basal cell skin cancer or squamous cell skin cancer)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Glycosylated Haemoglobin (HbA1c) | Week 0, Week 26 | Change from baseline in HbA1c after 26 weeks of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Body Weight | Week 0, Week 26 | Change from baseline in body weight after 26 weeks of treatment |
Countries
Bulgaria, Canada, France, Hungary, Netherlands, Romania, United States
Participant flow
Recruitment details
The trial was conducted at 89 sites in 7 countries: Bulgaria, Canada, France, Hungary, Netherlands, Romania, and United States.
Participants by arm
| Arm | Count |
|---|---|
| IDeg 3TW Insulin degludec (IDeg) 200 U/ml was given thrice weekly on Mondays, Wednesdays and Fridays subcutaneously (s.c.) in the evening with pre-trial metformin and with or without pre-trial DPP-4 for 26 weeks. | 233 |
| IGlar OD Insulin glargine (IGlar) was given once daily (OD) subcutaneously (s.c.) same time each day according to local labelling with pre-trial metformin and with or without pre-trial DPP-4 for 26 weeks. | 234 |
| Total | 467 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 1 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Protocol Violation | 7 | 9 |
| Overall Study | Unclassified | 12 | 12 |
| Overall Study | Withdrawal criteria | 2 | 2 |
Baseline characteristics
| Characteristic | IDeg 3TW | IGlar OD | Total |
|---|---|---|---|
| Age, Continuous | 57.3 years STANDARD_DEVIATION 9.6 | 57.5 years STANDARD_DEVIATION 10.7 | 57.4 years STANDARD_DEVIATION 10.2 |
| Body Weight | 92.3 kg STANDARD_DEVIATION 18.3 | 91.4 kg STANDARD_DEVIATION 18.7 | 91.8 kg STANDARD_DEVIATION 18.5 |
| Glycosylated haemoglobin (HbaA1c) | 8.3 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.8 | 8.3 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.8 | 8.3 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.8 |
| Sex: Female, Male Female | 101 Participants | 99 Participants | 200 Participants |
| Sex: Female, Male Male | 132 Participants | 135 Participants | 267 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 34 / 233 | 25 / 234 |
| serious Total, serious adverse events | 13 / 233 | 12 / 234 |
Outcome results
Primary
Change in Glycosylated Haemoglobin (HbA1c)
Change from baseline in HbA1c after 26 weeks of treatment
Time frame: Week 0, Week 26
Population: The Full analysis set (FAS) included all randomised subjects and missing data is imputed using last observation carried forward (LOCF).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IDeg 3TW | Change in Glycosylated Haemoglobin (HbA1c) | -1.05 percentage of glycosylated haemoglobin | Standard Deviation 0.94 |
| IGlar OD | Change in Glycosylated Haemoglobin (HbA1c) | -1.36 percentage of glycosylated haemoglobin | Standard Deviation 0.95 |
Secondary
Change in Body Weight
Change from baseline in body weight after 26 weeks of treatment
Time frame: Week 0, Week 26
Population: The FAS included all randomised subjects and missing data is imputed using last observation carried forward (LOCF).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IDeg 3TW | Change in Body Weight | 0.8 kg | Standard Deviation 3.9 |
| IGlar OD | Change in Body Weight | 0.5 kg | Standard Deviation 3.7 |