Diabetes, Diabetes Mellitus, Type 2
Conditions
Brief summary
This trial is conducted in Africa, Asia, Europe and the United States of America (USA). The aim of this clinical trial is to compare NN5401 (insulin degludec/insulin aspart) with insulin glargine in patients with type 2 diabetes inadequately controlled with insulin and oral anti-diabetic drugs (OADs). Subjects continued their ongoing treatment with OADs in the trial.
Interventions
DRUGinsulin degludec/insulin aspart
Treat-to-target dose titration scheme, injected subcutaneously (under the skin) once daily with main meal. Dose was individually adjusted.
DRUGinsulin glargine
Treat-to-target dose titration scheme, 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
* Type 2 diabetes mellitus (diagnosed clinically) for at least 6 months * Treatment with basal insulin regimen (insulin detemir, insulin glargine or neutral protamine Hagedorn \[NPH\] insulin) once daily (OD), for at least 3 months * Ongoing treatment with: metformin with or without other oral antidiabetic drugs (OADs) for at least 3 months prior to randomisation * HbA1c 7.0-10.0 % (both inclusive) by central laboratory analysis * BMI maximum 40.0 kg/m\^2
Exclusion criteria
* Treatment with insulin regimens other than a basal insulin regimen (insulin detemir or insulin glargine or NPH insulin) OD within 3 months prior to Visit 1 * Treatment with glucagon-like peptide 1 (GLP-1) receptor agonists within 3 months prior to visit 1 * Current rosiglitazone users * 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) * Impaired liver function, defined as alanine aminotransferase (ALAT) at least 2.5 times upper limit of normal (one retest analysed at the central laboratory within a week of receipt of the result is permitted with the result of the last sample being conclusive) * 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 |
|---|---|---|
| Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) | Week 26 | Mean of SMPG after 26 weeks of treatment. Plasma glucose measured: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner, bedtime, at 4 am and before breakfast. |
Countries
Croatia, France, India, Poland, South Africa, South Korea, Sweden, Turkey (Türkiye), United States
Participant flow
Recruitment details
The trial was conducted at 61 sites in 9 countries: Croatia (2 sites), France (4), India (8), Poland (4), South Africa (3), Republic of Korea (6), Sweden (5), Turkey (5) and United States of America (24).
Participants by arm
| Arm | Count |
|---|---|
| IDegAsp OD Insulin degludec/insulin aspart (IDegAsp) was given once daily (OD) subcutaneously (s.c.) with main evening meal or the largest meal of the day in combination with metformin±pioglitazone±DPP-4 inhibitor. | 230 |
| IGlar OD Insulin glargine (IGlar) was given once daily (OD) subcutaneously according to approved labelling in combination with metformin±pioglitazone±DPP-4. inhibitor. | 233 |
| Total | 463 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Lack of Efficacy | 3 | 1 |
| Overall Study | Protocol Violation | 6 | 3 |
| Overall Study | Unclassified | 17 | 13 |
| Overall Study | Withdrawal Criteria | 10 | 10 |
Baseline characteristics
| Characteristic | IDegAsp OD | IGlar OD | Total |
|---|---|---|---|
| Age, Continuous | 57.8 years STANDARD_DEVIATION 9.5 | 58.4 years STANDARD_DEVIATION 10.1 | 58.1 years STANDARD_DEVIATION 9.8 |
| Fasting plasma glucose (FPG) | 8.0 mmol/L STANDARD_DEVIATION 2.5 | 7.8 mmol/L STANDARD_DEVIATION 2.8 | 7.9 mmol/L STANDARD_DEVIATION 2.7 |
| Glycosylated haemoglobin (HbA1c) | 8.3 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.8 | 8.4 percentage of glycosylated haemoglobin STANDARD_DEVIATION 1 | 8.3 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.9 |
| Sex: Female, Male Female | 95 Participants | 106 Participants | 201 Participants |
| Sex: Female, Male Male | 135 Participants | 127 Participants | 262 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 51 / 230 | 62 / 233 |
| serious Total, serious adverse events | 10 / 230 | 8 / 233 |
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 was imputed using last observation carried forward (LOCF). Two subjects withdrew prior to exposure to trial drug, hence excluded from the FAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IDegAsp OD | Change in Glycosylated Haemoglobin (HbA1c) | -0.98 percentage of glycosylated haemoglobin | Standard Deviation 1.01 |
| IGlar OD | Change in Glycosylated Haemoglobin (HbA1c) | -1.00 percentage of glycosylated haemoglobin | Standard Deviation 1.06 |
Secondary
Mean of 9-point Self Measured Plasma Glucose Profile (SMPG)
Mean of SMPG after 26 weeks of treatment. Plasma glucose measured: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner, bedtime, at 4 am and before breakfast.
Time frame: Week 26
Population: The full analysis set (FAS) included all randomised subjects and missing data was imputed using last observation carried forward (LOCF). Two subjects withdrew prior to exposure to trial drug, hence excluded from the FAS. For 23 subjects all 9-point SMPG values were missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IDegAsp OD | Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) | 8.1 mmol/L | Standard Deviation 2 |
| IGlar OD | Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) | 8.4 mmol/L | Standard Deviation 2 |