Diabetes, Diabetes Mellitus, Type 2
Conditions
Brief summary
This trial is conducted in South Africa, Europe and North America. The aim of this trial is to compare efficacy and safety of NN1250 (insulin degludec (IDeg)) with insulin glargine (IGlar), as add-on to subject's ongoing treatment with metformin and/or dipeptyl peptidase 4 (DPP-4) inhibitors, in patients with type 2 diabetes being treated with oral anti-diabetic drugs (OADs) qualifying for intensified treatment.
Interventions
DRUGinsulin degludec
Injected subcutaneously (under the skin) once daily. 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 an insulin secretagogue (sulfonylurea or glinide), DPP-4 inhibitor, alpha-glucosidase-inhibitors (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 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-inhibitors (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) maximum 45.0 kg/m\^2 * Type 2 diabetes (diagnosed clinically) for at least 6 months * Ability and willingness to adhere to the protocol including performance of self monitored plasma glucose (SMPG) profiles according to the protocol
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 \[for UK: adequate contraceptive measures are defined as established use of oral, injected or implanted hormonal methods of contraception, sterilisation, intrauterine device or intrauterine system, or consistent use of barrier methods\] * 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 0, Week 26 | Change from baseline in HbA1c after 26 weeks of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Fasting Plasma Glucose (FPG) | Week 0, Week 26 | Change from baseline in FPG after 26 weeks of treatment |
Countries
Canada, France, Ireland, Russia, South Africa, Ukraine, United Kingdom, United States
Participant flow
Recruitment details
The trial was conducted at 106 sites in 8 countries: Canada (11), France (6), Ireland (3), Russian Federation (7), South Africa (4), Ukraine (2), United Kingdom (18) and United States of America (55).
Pre-assignment details
Subjects continued on metformin with or without dipeptidyl peptidase-4 (DPP-4) inhibitors at the pre-randomisation dose level and dosing frequency.
Participants by arm
| Arm | Count |
|---|---|
| IDeg 200 U/mL OD Insulin degludec (IDeg) 200U/mL was given once daily (OD) subcutaneously with the main evening meal in combination with metformin with or without dipeptidyl peptidase-4 (DPP-4) inhibitor treatment for 26 weeks. | 228 |
| IGlar OD Insulin glargine (IGlar) was given once daily (OD) subcutaneously according to approved labelling in combination with metformin with or without dipeptidyl peptidase-4 (DPP-4) inhibitor treatment for 26 weeks. | 229 |
| Total | 457 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 4 |
| Overall Study | Lack of Efficacy | 0 | 2 |
| Overall Study | Other | 17 | 12 |
| Overall Study | Protocol Violation | 5 | 2 |
| Overall Study | Withdrawal Criteria | 3 | 9 |
Baseline characteristics
| Characteristic | IDeg 200 U/mL OD | IGlar OD | Total |
|---|---|---|---|
| Age, Continuous | 57.8 years STANDARD_DEVIATION 9 | 57.3 years STANDARD_DEVIATION 9.4 | 57.5 years STANDARD_DEVIATION 9.2 |
| Fasting plasma glucose (FPG) | 9.6 mmol/L STANDARD_DEVIATION 2.9 | 9.7 mmol/L STANDARD_DEVIATION 2.6 | 9.6 mmol/L STANDARD_DEVIATION 2.7 |
| Glycosylated haemoglobin (HbA1c) | 8.3 percentage of glycosylated haemoglobin STANDARD_DEVIATION 1 | 8.2 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.9 | 8.3 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.9 |
| Sex: Female, Male Female | 109 Participants | 105 Participants | 214 Participants |
| Sex: Female, Male Male | 119 Participants | 124 Participants | 243 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 51 / 228 | 60 / 228 |
| serious Total, serious adverse events | 15 / 228 | 10 / 228 |
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: Full analysis set (FAS) includes all randomised subjects and missing data was imputed using last observation carried forward (LOCF). 2 subjects were withdrawn prior to exposure to the study drug in the IDeg arm as they were randomised in error and 1 subject in the IGlar arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IDeg 200 U/mL OD | Change in Glycosylated Haemoglobin (HbA1c) | -1.30 percentage of glycosylated haemoglobin | Standard Deviation 1.04 |
| IGlar OD | Change in Glycosylated Haemoglobin (HbA1c) | -1.32 percentage of glycosylated haemoglobin | Standard Deviation 0.98 |
Secondary
Change in Fasting Plasma Glucose (FPG)
Change from baseline in FPG after 26 weeks of treatment
Time frame: Week 0, Week 26
Population: The FAS included all randomised subjects and missing data was imputed using last observation carried forward (LOCF). For 3 subjects baseline values were missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IDeg 200 U/mL OD | Change in Fasting Plasma Glucose (FPG) | -3.70 mmol/L | Standard Deviation 3.06 |
| IGlar OD | Change in Fasting Plasma Glucose (FPG) | -3.38 mmol/L | Standard Deviation 2.96 |