Diabetes, Diabetes Mellitus, Type 2
Conditions
Brief summary
Trial comparing effect and safety of insulin degludec/insulin aspart vs. insulin glargine plus insulin aspart in subjects with type 2 diabetes treated with basal insulin with or without oral antidiabetic treatment in need of treatment intensification.
Interventions
DRUGInsulin degludec/insulin aspart
Administered subcutaneously (s.c. under the skin) once daily.
DRUGInsulin glargine
Administered subcutaneously (s.c. under the skin) once daily.
DRUGInsulin aspart
Administered subcutaneously (s.c. under the skin) once daily.
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
* Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial * Male or female, age at least 18 years at the time of signing informed consent Algeria: Male or female, age at least 19 years at the time of signing informed consent * Diagnosed with type 2 diabetes mellitus * Treated with any basal insulin for at least 90 days prior to the day of screening * Subject not on any OAD(s) prior to trial participation OR subjects on stable daily dose(s) of OAD(s) for at least 90 days prior to screening visit (V1). The OAD(s) include any of the following anti-diabetic drug s)/regimen: a. Biguanides (metformin at least 1500 mg or maximum tolerated dose documented in the subject medical record) b. Other OADs (at least half of the maximum approved dose according to local label or maximum tolerated dose as documented in subject medical record): i. Insulin secretagogues (SU and glinides) ii. Di-peptidyl-peptidase IV (DPP-4) inhibitors iii. α-glucosidase inhibitors iv. Sodium/glucose co-transporter 2 (SGLT-2) inhibitors v. Oral combination products (of the allowed individual OADs above) * HbA1c 7.0-10.0% (53-86 mmol/mol) (both inclusive) by central laboratory analysis * Body mass index (BMI) equal to or below 45.0 kg/m\^2
Exclusion criteria
* Participation in any clinical trial of an approved or non-approved investigational medicinal product within four weeks prior to the day of screening (V1) * Any chronic disorder or severe disease which, in the opinion of the investigator, might jeopardise subject's safety or compliance with the protocol * Acute decompensation of glycaemic control requiring immediate intensification of treatment to prevent severe metabolic dysregulation (e.g. diabetes ketoacidosis) equal or below 90 days prior to the day of the screening and between screening and randomisation * Any of the following: myocardial infarction, stroke or hospitalization for unstable angina or transient ischaemic attack within the past 180 days prior to the day of screening and between screening and randomisation * Renal impairment measured as estimated Glomerular Filtration Rate (eGFR) value of below 60 ml/min/1.73 m\^2 as defined by KDIGO 2012 classification using isotope dilution mass spectrometry (IDMS) for serum creatinine measured at screening * Impaired liver function, defined as alanine aminotransferase (ALT) equal to or above 2.5 times upper normal limit (UNL) at screening. * Subjects presently classified as being in New York Heart Association (NYHA) Class IV * Planned coronary, carotid or peripheral artery revascularisation known on the day of screening * Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria in a period of 90 days before the day of screening * Anticipated initiation or change in concomitant medications (for more than 14 consecutive days) known to affect weight or glucose metabolism (e.g. treatment with orlistat, thyroid hormones, or corticosteroids)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1c (%) - Week 26 | Week 0, week 26 | Change from baseline (week 0) in glycosylated haemoglobin (HbA1c) was evaluated 26 weeks after randomisation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Responder (Yes/No) for HbA1c < 7% | Week 26 and week 38 | Participants achieving (yes/no) HbA1c \<7% was evaluated 26 and 38 weeks after randomisation, respectively. |
| Responder (Yes/No) for HbA1c <7% Without Severe or BG Confirmed Symptomatic Hypoglycaemia | Week 26 and week 38 | Participants achieving (yes/no) HbA1c \<7% without severe or blood glucose (BG) confirmed symptomatic hypoglycaemia, was evaluated 26 and 38 weeks after randomisation, respectively. Severe or BG confirmed symptomatic hypoglycaemia: An episode that is severe according to the American Diabetes Association (ADA) classification or BG confirmed by a plasma glucose value \<3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. Severe hypoglycaemia as per ADA classification: An episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. Plasma glucose concentrations may not be available during an event, but neurological recovery following the return of plasma glucose to normal is considered sufficient evidence that the event was induced by a low plasma glucose concentration. |
| Change in FPG | Week 0, week 26, week 38 | Change from baseline (week 0) in fasting plasma glucose (FPG) was evaluated 26 and 38 weeks after randomisation, respectively. |
| Change in Pre-breakfast SMPG (Used for Titration) | Week 1, week 26, week 38 | Reported results are observed pre-breakfast self-measured plasma glucose (SMPG; used for titration) values at week 1 (baseline) and 26 and 38 weeks after randomisation. |
| Change in Postprandial SMPG Increment (From 9-point Profile) | Week 0, week 26, week 38 | Change from baseline (week 0) in postprandial SMPG increment (from 9-point profile) was evaluated 26 and 38 weeks after randomisation, respectively. 9-point SMPG profiles were measured starting in the morning 2 days prior to the scheduled visit at the time points described below: 1) Before breakfast (2 days prior to visit) 2) 90 minutes after start of the breakfast 3) Before lunch 4) 90 minutes after start of the lunch 5) Before dinner/main evening meal 6) 90 minutes after start of the dinner/main evening meal 7) At bedtime (2 days or 1 day prior to visit depending on actual clock time) 8) At 4 a.m. (1 day prior to visit) 9) Before breakfast at the following day (1 day prior to the visit). |
| Change in HbA1c (%) - Week 38 | Week 0, week 38 | Change from baseline (week 0) in HbA1c was evaluated 38 weeks after randomisation. |
| Number of Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes | Weeks 0-26, weeks 16-26, weeks 0-38 | Number of treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were analysed during the following periods: weeks 0-26, weeks 16-26 and weeks 0-38. Treatment emergent: hypoglycaemic episodes were defined as treatment emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product. |
| Total Insulin Dose | Week 26 and week 38 | Total insulin dose was evaluated 26 and 38 weeks after randomisation, respectively. |
| Change in Body Weight | Week 0, week 26, week 38 | Change from baseline (week 0) in body weight was evaluated 26 and 38 weeks after randomisation, respectively. |
| Incidence of TEAEs | Weeks 0-26, weeks 26-38, weeks 0-38 | Number of treatment emergent adverse events (TEAEs) were analysed during the following periods: weeks 0-26, weeks 26-38 and weeks 0-38. Treatment emergent: An adverse event that had an onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment. If an event had an onset date before the first day of exposure on randomised treatment and increased in severity during the treatment period, or if it had an onset date within 7 days after the last drug date, then this event was also to be considered as a TEAE. |
| Number of Nocturnal, Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes | Weeks 0-26, weeks 16-26, weeks 0-38 | Number of nocturnal, treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were analysed during the following periods: weeks 0-26, weeks 16-26 and weeks 0-38. Nocturnal hypoglycaemic episodes: episodes occurring between 00:01 and 05:59 both inclusive. Treatment emergent: hypoglycaemic episodes were defined as treatment emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product. |
Countries
Algeria, Czechia, India, Russia, Serbia, Turkey (Türkiye), United States
Participant flow
Recruitment details
The trial was conducted at 71 sites in 7 countries, as follows: Algeria (4), Czech Republic (6), India (10), Russian Federation (11), Serbia (5), Turkey (7), and United States (28). Additionally, 1 site in the United States screened, but didn't randomise any subject.
Participants by arm
| Arm | Count |
|---|---|
| Insulin Degludec/Insulin Aspart Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): IDegAsp OD administered at the largest meal each day with or without OAD(s). Subjects switching from pre-trial basal insulin OD or more to IDegAsp OD at trial entry were to transfer unit-to-unit. 2) Intensification period (period-2, week 26-38): IDegAsp OD/BID administered at the largest meal(s) each day (in the case of BID dosing, one meal being dinner) based on individual needs with or without OAD(s). | 267 |
| Insulin Glargine + Insulin Aspart Subjects received treatment for 38 weeks as per the following sequence: 1) Initiation period (period-1, week 0-26): Insulin glargine (IGlar) OD administered in accordance with local labelling and insulin aspart (IAsp) OD administered at the largest meal with or without OAD(s). Subjects switching from pre-trial basal insulin OD to IGlar OD were also to transfer unit-to-unit to IGlar, while subjects switching from basal insulin more than OD to IGlar OD were to reduce the initial total daily dose by 20% or according to local labelling. IAsp was to be initiated at 4 units with the largest meal. 2) Intensification period (period-2, week 26-38): IGlar OD administered in accordance with local labelling and IAsp 1-3 times daily administered at main meals based on individual needs with or without OAD(s). | 265 |
| Total | 532 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Initiation Period (Week 0-26) | Adverse Event | 1 | 0 |
| Initiation Period (Week 0-26) | Lost to Follow-up | 1 | 4 |
| Initiation Period (Week 0-26) | Unclassified | 1 | 3 |
| Initiation Period (Week 0-26) | Withdrawal by Subject | 3 | 4 |
| Intensification Period (Week 26-38) | Adverse Event | 0 | 2 |
| Intensification Period (Week 26-38) | Lost to Follow-up | 3 | 1 |
| Intensification Period (Week 26-38) | Unclassified | 3 | 2 |
| Intensification Period (Week 26-38) | Withdrawal by Subject | 3 | 2 |
Baseline characteristics
| Characteristic | Insulin Glargine + Insulin Aspart | Total | Insulin Degludec/Insulin Aspart |
|---|---|---|---|
| Age, Continuous | 59.2 Years STANDARD_DEVIATION 9.1 | 58.7 Years STANDARD_DEVIATION 9 | 58.2 Years STANDARD_DEVIATION 8.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 20 Participants | 41 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 245 Participants | 491 Participants | 246 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 32 Participants | 61 Participants | 29 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 24 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) White | 220 Participants | 441 Participants | 221 Participants |
| Sex: Female, Male Female | 128 Participants | 270 Participants | 142 Participants |
| Sex: Female, Male Male | 137 Participants | 262 Participants | 125 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 265 | 2 / 263 |
| other Total, other adverse events | 74 / 265 | 57 / 263 |
| serious Total, serious adverse events | 18 / 265 | 20 / 263 |
Outcome results
Primary
Change in HbA1c (%) - Week 26
Change from baseline (week 0) in glycosylated haemoglobin (HbA1c) was evaluated 26 weeks after randomisation.
Time frame: Week 0, week 26
Population: FAS, which included all randomised subjects. Number of subjects analyzed = number of subjects contributed to the analysis at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Degludec/Insulin Aspart | Change in HbA1c (%) - Week 26 | Baseline (week 0) | 8.2 % of HbA1c | Standard Deviation 0.8 |
| Insulin Degludec/Insulin Aspart | Change in HbA1c (%) - Week 26 | Change from baseline (week 26) | -1.1 % of HbA1c | Standard Deviation 0.9 |
| Insulin Glargine + Insulin Aspart | Change in HbA1c (%) - Week 26 | Baseline (week 0) | 8.1 % of HbA1c | Standard Deviation 0.7 |
| Insulin Glargine + Insulin Aspart | Change in HbA1c (%) - Week 26 | Change from baseline (week 26) | -1.1 % of HbA1c | Standard Deviation 0.8 |
Comparison: The response and change from baseline in response are analysed on 1000 complete, imputed data sets after multiple imputation for each treatment arm separately. A penalty of 0.4% is added to the week 26 values for all premature treatment discontinued subjects, and subject with missing HbA1c values at week 26 in the IDegAsp arm. Each of the imputed data sets are analysed through an analysis of covariance (ANCOVA).p-value: <0.000195% CI: [-0.06, 0.21]ANCOVA
Secondary
Change in Body Weight
Change from baseline (week 0) in body weight was evaluated 26 and 38 weeks after randomisation, respectively.
Time frame: Week 0, week 26, week 38
Population: Safety analysis set, which included all subjects receiving at least one dose of the investigational product or comparator. Number of subjects analyzed = number of subjects contributed to the analysis at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Degludec/Insulin Aspart | Change in Body Weight | Baseline: Week 0 | 88.5 Kg | Standard Deviation 18.6 |
| Insulin Degludec/Insulin Aspart | Change in Body Weight | Change from basline: Week 26 | 1.7 Kg | Standard Deviation 3.2 |
| Insulin Degludec/Insulin Aspart | Change in Body Weight | Change from basline: Week 38 | 2.5 Kg | Standard Deviation 3.8 |
| Insulin Glargine + Insulin Aspart | Change in Body Weight | Baseline: Week 0 | 88.4 Kg | Standard Deviation 17.5 |
| Insulin Glargine + Insulin Aspart | Change in Body Weight | Change from basline: Week 26 | 1.4 Kg | Standard Deviation 3.2 |
| Insulin Glargine + Insulin Aspart | Change in Body Weight | Change from basline: Week 38 | 2.4 Kg | Standard Deviation 3.2 |
Secondary
Change in FPG
Change from baseline (week 0) in fasting plasma glucose (FPG) was evaluated 26 and 38 weeks after randomisation, respectively.
Time frame: Week 0, week 26, week 38
Population: FAS, which included all randomised subjects. Number of subjects analyzed = number of subjects contributed to the analysis at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Degludec/Insulin Aspart | Change in FPG | Baseline: Week 0 | 162.4 mg/dL | Standard Deviation 47.8 |
| Insulin Degludec/Insulin Aspart | Change in FPG | Change from baseline: Week 26 | -42.1 mg/dL | Standard Deviation 52.1 |
| Insulin Degludec/Insulin Aspart | Change in FPG | Change from baseline: Week 38 | -48.6 mg/dL | Standard Deviation 54.2 |
| Insulin Glargine + Insulin Aspart | Change in FPG | Baseline: Week 0 | 157.8 mg/dL | Standard Deviation 47.8 |
| Insulin Glargine + Insulin Aspart | Change in FPG | Change from baseline: Week 26 | -40.6 mg/dL | Standard Deviation 59.2 |
| Insulin Glargine + Insulin Aspart | Change in FPG | Change from baseline: Week 38 | -41.5 mg/dL | Standard Deviation 55.3 |
Secondary
Change in HbA1c (%) - Week 38
Change from baseline (week 0) in HbA1c was evaluated 38 weeks after randomisation.
Time frame: Week 0, week 38
Population: FAS, which included all randomised subjects. Number of subjects analyzed = number of subjects contributed to the analysis at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Degludec/Insulin Aspart | Change in HbA1c (%) - Week 38 | Baseline (week 0) | 8.2 % of HbA1c | Standard Deviation 0.8 |
| Insulin Degludec/Insulin Aspart | Change in HbA1c (%) - Week 38 | Change from baseline (week 38) | -1.2 % of HbA1c | Standard Deviation 0.9 |
| Insulin Glargine + Insulin Aspart | Change in HbA1c (%) - Week 38 | Baseline (week 0) | 8.1 % of HbA1c | Standard Deviation 0.7 |
| Insulin Glargine + Insulin Aspart | Change in HbA1c (%) - Week 38 | Change from baseline (week 38) | -1.2 % of HbA1c | Standard Deviation 0.9 |
Secondary
Change in Postprandial SMPG Increment (From 9-point Profile)
Change from baseline (week 0) in postprandial SMPG increment (from 9-point profile) was evaluated 26 and 38 weeks after randomisation, respectively. 9-point SMPG profiles were measured starting in the morning 2 days prior to the scheduled visit at the time points described below: 1) Before breakfast (2 days prior to visit) 2) 90 minutes after start of the breakfast 3) Before lunch 4) 90 minutes after start of the lunch 5) Before dinner/main evening meal 6) 90 minutes after start of the dinner/main evening meal 7) At bedtime (2 days or 1 day prior to visit depending on actual clock time) 8) At 4 a.m. (1 day prior to visit) 9) Before breakfast at the following day (1 day prior to the visit).
Time frame: Week 0, week 26, week 38
Population: FAS, which included all randomised subjects. Number of subjects analyzed = number of subjects contributed to the analysis at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Degludec/Insulin Aspart | Change in Postprandial SMPG Increment (From 9-point Profile) | Baseline: Week 0 | 54.5 mg/dL | Standard Deviation 37.7 |
| Insulin Degludec/Insulin Aspart | Change in Postprandial SMPG Increment (From 9-point Profile) | Change from baseline: Week 26 | -10.8 mg/dL | Standard Deviation 46.3 |
| Insulin Degludec/Insulin Aspart | Change in Postprandial SMPG Increment (From 9-point Profile) | Change from baseline: Week 38 | -17.7 mg/dL | Standard Deviation 40 |
| Insulin Glargine + Insulin Aspart | Change in Postprandial SMPG Increment (From 9-point Profile) | Baseline: Week 0 | 48.4 mg/dL | Standard Deviation 38 |
| Insulin Glargine + Insulin Aspart | Change in Postprandial SMPG Increment (From 9-point Profile) | Change from baseline: Week 26 | -8.7 mg/dL | Standard Deviation 40.6 |
| Insulin Glargine + Insulin Aspart | Change in Postprandial SMPG Increment (From 9-point Profile) | Change from baseline: Week 38 | -19.7 mg/dL | Standard Deviation 45 |
Secondary
Change in Pre-breakfast SMPG (Used for Titration)
Reported results are observed pre-breakfast self-measured plasma glucose (SMPG; used for titration) values at week 1 (baseline) and 26 and 38 weeks after randomisation.
Time frame: Week 1, week 26, week 38
Population: FAS, which included all randomised subjects. Number of subjects analyzed = number of subjects contributed to the analysis at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Degludec/Insulin Aspart | Change in Pre-breakfast SMPG (Used for Titration) | Week 1 (Baseline) | 158.3 mg/dL | Standard Deviation 45.7 |
| Insulin Degludec/Insulin Aspart | Change in Pre-breakfast SMPG (Used for Titration) | Week 26 | 107.5 mg/dL | Standard Deviation 24.8 |
| Insulin Degludec/Insulin Aspart | Change in Pre-breakfast SMPG (Used for Titration) | Week 38 | 102.9 mg/dL | Standard Deviation 20 |
| Insulin Glargine + Insulin Aspart | Change in Pre-breakfast SMPG (Used for Titration) | Week 1 (Baseline) | 149.4 mg/dL | Standard Deviation 43.8 |
| Insulin Glargine + Insulin Aspart | Change in Pre-breakfast SMPG (Used for Titration) | Week 26 | 103.4 mg/dL | Standard Deviation 20.7 |
| Insulin Glargine + Insulin Aspart | Change in Pre-breakfast SMPG (Used for Titration) | Week 38 | 103.8 mg/dL | Standard Deviation 22.5 |
Secondary
Incidence of TEAEs
Number of treatment emergent adverse events (TEAEs) were analysed during the following periods: weeks 0-26, weeks 26-38 and weeks 0-38. Treatment emergent: An adverse event that had an onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment. If an event had an onset date before the first day of exposure on randomised treatment and increased in severity during the treatment period, or if it had an onset date within 7 days after the last drug date, then this event was also to be considered as a TEAE.
Time frame: Weeks 0-26, weeks 26-38, weeks 0-38
Population: Safety analysis set, which included all subjects receiving at least one dose of the investigational product (IDegAsp) or comparator (IGlar). Number of subjects analyzed = number of subjects contributed to the analysis at specified time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Insulin Degludec/Insulin Aspart | Incidence of TEAEs | Weeks 0-38 | 614 Events |
| Insulin Degludec/Insulin Aspart | Incidence of TEAEs | Weeks 0-26 | 441 Events |
| Insulin Degludec/Insulin Aspart | Incidence of TEAEs | Weeks 26-38 | 173 Events |
| Insulin Glargine + Insulin Aspart | Incidence of TEAEs | Weeks 0-38 | 525 Events |
| Insulin Glargine + Insulin Aspart | Incidence of TEAEs | Weeks 0-26 | 408 Events |
| Insulin Glargine + Insulin Aspart | Incidence of TEAEs | Weeks 26-38 | 117 Events |
Secondary
Number of Nocturnal, Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes
Number of nocturnal, treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were analysed during the following periods: weeks 0-26, weeks 16-26 and weeks 0-38. Nocturnal hypoglycaemic episodes: episodes occurring between 00:01 and 05:59 both inclusive. Treatment emergent: hypoglycaemic episodes were defined as treatment emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product.
Time frame: Weeks 0-26, weeks 16-26, weeks 0-38
Population: Safety analysis set, which included all subjects receiving at least one dose of the investigational product (IDegAsp) or comparator (IGlar). Number of subjects analyzed = number of subjects contributed to the analysis at specified time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Insulin Degludec/Insulin Aspart | Number of Nocturnal, Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes | Weeks 0-26 | 61 Episodes |
| Insulin Degludec/Insulin Aspart | Number of Nocturnal, Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes | Weeks 16-26 | 24 Episodes |
| Insulin Degludec/Insulin Aspart | Number of Nocturnal, Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes | Weeks 0-38 | 113 Episodes |
| Insulin Glargine + Insulin Aspart | Number of Nocturnal, Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes | Weeks 0-26 | 118 Episodes |
| Insulin Glargine + Insulin Aspart | Number of Nocturnal, Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes | Weeks 16-26 | 58 Episodes |
| Insulin Glargine + Insulin Aspart | Number of Nocturnal, Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes | Weeks 0-38 | 189 Episodes |
Secondary
Number of Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes
Number of treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were analysed during the following periods: weeks 0-26, weeks 16-26 and weeks 0-38. Treatment emergent: hypoglycaemic episodes were defined as treatment emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 7 calendar days after the last day on trial product.
Time frame: Weeks 0-26, weeks 16-26, weeks 0-38
Population: Safety analysis set, which included all subjects receiving at least one dose of the investigational product or comparator. Number of subjects analyzed = number of subjects contributed to the analysis at specified time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Insulin Degludec/Insulin Aspart | Number of Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes | Weeks 0-26 | 329 Episodes |
| Insulin Degludec/Insulin Aspart | Number of Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes | Weeks 16-26 | 154 Episodes |
| Insulin Degludec/Insulin Aspart | Number of Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes | Weeks 0-38 | 537 Episodes |
| Insulin Glargine + Insulin Aspart | Number of Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes | Weeks 0-26 | 376 Episodes |
| Insulin Glargine + Insulin Aspart | Number of Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes | Weeks 16-26 | 194 Episodes |
| Insulin Glargine + Insulin Aspart | Number of Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes | Weeks 0-38 | 640 Episodes |
Secondary
Responder (Yes/No) for HbA1c < 7%
Participants achieving (yes/no) HbA1c \<7% was evaluated 26 and 38 weeks after randomisation, respectively.
Time frame: Week 26 and week 38
Population: FAS, which included all randomised subjects. Number of subjects analyzed = number of subjects contributed to the analysis at specified time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Insulin Degludec/Insulin Aspart | Responder (Yes/No) for HbA1c < 7% | Week 26: Yes | 120 Number of participants |
| Insulin Degludec/Insulin Aspart | Responder (Yes/No) for HbA1c < 7% | Week 26: No | 121 Number of participants |
| Insulin Degludec/Insulin Aspart | Responder (Yes/No) for HbA1c < 7% | Week 38: Yes | 139 Number of participants |
| Insulin Degludec/Insulin Aspart | Responder (Yes/No) for HbA1c < 7% | Week 38: No | 95 Number of participants |
| Insulin Glargine + Insulin Aspart | Responder (Yes/No) for HbA1c < 7% | Week 38: No | 93 Number of participants |
| Insulin Glargine + Insulin Aspart | Responder (Yes/No) for HbA1c < 7% | Week 26: Yes | 120 Number of participants |
| Insulin Glargine + Insulin Aspart | Responder (Yes/No) for HbA1c < 7% | Week 38: Yes | 140 Number of participants |
| Insulin Glargine + Insulin Aspart | Responder (Yes/No) for HbA1c < 7% | Week 26: No | 122 Number of participants |
Secondary
Responder (Yes/No) for HbA1c <7% Without Severe or BG Confirmed Symptomatic Hypoglycaemia
Participants achieving (yes/no) HbA1c \<7% without severe or blood glucose (BG) confirmed symptomatic hypoglycaemia, was evaluated 26 and 38 weeks after randomisation, respectively. Severe or BG confirmed symptomatic hypoglycaemia: An episode that is severe according to the American Diabetes Association (ADA) classification or BG confirmed by a plasma glucose value \<3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. Severe hypoglycaemia as per ADA classification: An episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. Plasma glucose concentrations may not be available during an event, but neurological recovery following the return of plasma glucose to normal is considered sufficient evidence that the event was induced by a low plasma glucose concentration.
Time frame: Week 26 and week 38
Population: FAS, which included all randomised subjects. Number of subjects analyzed = number of subjects contributed to the analysis at specified time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Insulin Degludec/Insulin Aspart | Responder (Yes/No) for HbA1c <7% Without Severe or BG Confirmed Symptomatic Hypoglycaemia | Week 26: Yes | 73 Number of participants |
| Insulin Degludec/Insulin Aspart | Responder (Yes/No) for HbA1c <7% Without Severe or BG Confirmed Symptomatic Hypoglycaemia | Week 26: No | 168 Number of participants |
| Insulin Degludec/Insulin Aspart | Responder (Yes/No) for HbA1c <7% Without Severe or BG Confirmed Symptomatic Hypoglycaemia | Week 38: Yes | 60 Number of participants |
| Insulin Degludec/Insulin Aspart | Responder (Yes/No) for HbA1c <7% Without Severe or BG Confirmed Symptomatic Hypoglycaemia | Week 38: No | 174 Number of participants |
| Insulin Glargine + Insulin Aspart | Responder (Yes/No) for HbA1c <7% Without Severe or BG Confirmed Symptomatic Hypoglycaemia | Week 38: No | 177 Number of participants |
| Insulin Glargine + Insulin Aspart | Responder (Yes/No) for HbA1c <7% Without Severe or BG Confirmed Symptomatic Hypoglycaemia | Week 26: Yes | 61 Number of participants |
| Insulin Glargine + Insulin Aspart | Responder (Yes/No) for HbA1c <7% Without Severe or BG Confirmed Symptomatic Hypoglycaemia | Week 38: Yes | 56 Number of participants |
| Insulin Glargine + Insulin Aspart | Responder (Yes/No) for HbA1c <7% Without Severe or BG Confirmed Symptomatic Hypoglycaemia | Week 26: No | 181 Number of participants |
Secondary
Total Insulin Dose
Total insulin dose was evaluated 26 and 38 weeks after randomisation, respectively.
Time frame: Week 26 and week 38
Population: Safety analysis set, which included all subjects receiving at least one dose of the investigational product or comparator. Number of subjects analyzed = number of subjects contributed to the analysis at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Degludec/Insulin Aspart | Total Insulin Dose | Week 26 | 70.9 Units | Standard Deviation 41.5 |
| Insulin Degludec/Insulin Aspart | Total Insulin Dose | Week 38 | 83.4 Units | Standard Deviation 51.3 |
| Insulin Glargine + Insulin Aspart | Total Insulin Dose | Week 26 | 79.4 Units | Standard Deviation 37.7 |
| Insulin Glargine + Insulin Aspart | Total Insulin Dose | Week 38 | 89.3 Units | Standard Deviation 43.1 |