Diabetes, Diabetes Mellitus, Type 2
Conditions
Brief summary
This trial is conducted in Africa, Asia, Europe, and North America. The aim of this clinical trial is to compare the efficacy and safety of NN1250 (insulin degludec (IDeg)) with insulin glargine (IGlar) in subjects with type 2 diabetes currently treated with metformin alone or with metformin combined with an oral anti-diabetic drug (OAD) qualifying for intensified treatment.
Interventions
DRUGinsulin degludec
Injected subcutaneously (under the skin) three times weekly. Dose was individually adjusted.
DRUGinsulin glargine
Injected subcutaneously (under the skin) once daily. Dose was individually adjusted.
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
* Insulin naïve subject (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 three 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 secretaguogue (sulfonylurea 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 * Body Mass Index (BMI) below or equal to 45.0 kg/m\^2
Exclusion criteria
* Use within the last 3 months prior to Visit 1 of: thiazoledinediones, 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 (for UK: adequate contraceptive measures are defined as established use of oral, injected or implanted hormonal methods of contraception, sterilisation, intrauterine device or intrauterine system, or consistent use of barrier methods) * 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 26 | Change from baseline in HbA1c after week 26 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Body Weight | Week 26 | Change from baseline in body weight after week 26 |
Countries
Canada, Czechia, Israel, Puerto Rico, Slovakia, South Africa, United Kingdom, United States
Participant flow
Recruitment details
The trial was conducted at 94 sites in 7 countries: Canada (14 sites), Czech Republic (5 sites), Israel (5 sites), Slovakia (5 sites), South Africa (3 sites), United Kingdom (8 sites) and United States (54 sites). In addition, 9 sites (United Kingdom (1 site) and United States (8 sites)) were approved, but did not enroll any subjects.
Participants by arm
| Arm | Count |
|---|---|
| IDeg 3TW Insulin degludec (IDeg) 200U/mL given 3 times weekly (Mondays, Wednesdays, Fridays) in the morning with metformin with or without dipeptidyl peptidase-4 (DPP-4) inhibitor treatment for 26 weeks. | 229 |
| IGlar OD Insulin glargine (IGlar) 100U/mL given once a day (OD), according to the labelling instructions with metformin with or without dipeptidyl peptidase-4 (DPP-4) inhibitor treatment for 26 weeks. | 230 |
| Total | 459 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lack of Efficacy | 3 | 2 |
| Overall Study | Protocol Violation | 5 | 1 |
| Overall Study | Unclassified | 18 | 15 |
| Overall Study | Withdrawal criteria | 12 | 6 |
Baseline characteristics
| Characteristic | IGlar OD | Total | IDeg 3TW |
|---|---|---|---|
| Age, Continuous | 57.9 years STANDARD_DEVIATION 9.7 | 58.1 years STANDARD_DEVIATION 9.8 | 58.4 years STANDARD_DEVIATION 9.9 |
| Body weight | 95.7 kg STANDARD_DEVIATION 19 | 93.3 kg STANDARD_DEVIATION 18.9 | 90.8 kg STANDARD_DEVIATION 18.6 |
| Fasting Plasma Glucose | 9.6 mmol/L STANDARD_DEVIATION 2.4 | 9.5 mmol/L STANDARD_DEVIATION 2.4 | 9.3 mmol/L STANDARD_DEVIATION 2.4 |
| Glycosylated haemoglobin (HbA1c) | 8.3 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.9 | 8.2 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.8 | 8.2 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.8 |
| Sex: Female, Male Female | 93 Participants | 198 Participants | 105 Participants |
| Sex: Female, Male Male | 137 Participants | 261 Participants | 124 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 69 / 227 | 77 / 229 |
| serious Total, serious adverse events | 11 / 227 | 4 / 229 |
Outcome results
Primary
Change in Glycosylated Haemoglobin (HbA1c)
Change from baseline in HbA1c after week 26
Time frame: Week 26
Population: The Full analysis set (FAS) included all randomised subjects and missing data is imputed using last observation carried forward (LOCF).1 subject was randomised despite being a screening failure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IDeg 3TW | Change in Glycosylated Haemoglobin (HbA1c) | -1.00 percentage of glycosylated haemoglobin | Standard Deviation 0.95 |
| IGlar OD | Change in Glycosylated Haemoglobin (HbA1c) | -1.40 percentage of glycosylated haemoglobin | Standard Deviation 1.07 |
Secondary
Change in Body Weight
Change from baseline in body weight after week 26
Time frame: Week 26
Population: The Safety analysis set (SAS) included all subjects who received at least one dose of the investigational product or its comparator. Missing data is imputed using last observation carried forward (LOCF). For 3 subjects baseline values were missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IDeg 3TW | Change in Body Weight | 0.8 kg | Standard Deviation 3.6 |
| IGlar OD | Change in Body Weight | 1.0 kg | Standard Deviation 3.7 |