Diabetes, Diabetes Mellitus, Type 2
Conditions
Brief summary
This trial is conducted in Europe and North America. The aim of the trial is to compare the efficacy and safety of insulin degludec and insulin glargine 300 units/mL in subjects with type 2 diabetes mellitus inadequately treated with basal insulin with or without oral antidiabetic drugs. Due to change in glycaemic data collection process, this trial is amended to allow for a full 36 weeks (maintenance 2 period) of the use of the new process.
Interventions
DRUGInsulin degludec
For subcutaneous (s.c., under the skin) injection once daily
DRUGInsulin glargine
For subcutaneous (s.c., under the skin) injection 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
- Male or female, age above or equal to 18 years at the time of signing informed consent. - Subjects fulfilling at least one of the below criteria (For this inclusion criterion the aim is to include minimum 80% of individuals with a previous episode of hypoglycaemia (criterion e). The remaining subjects will have to fulfil at least one of criteria a-d.): - a) Experienced at least one severe hypoglycaemic episode within the last year (according to the ADA definition, April 2013 (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.). - b) Moderate chronic renal failure, defined as glomerular filtration rate 30 - 59 mL/min/1.73 m\^2 per CKD-EPI by central laboratory analysis. - c) Hypoglycaemic symptom unawareness (History of impaired autonomic responses (tremulousness, sweating, palpitations, and hunger) during hypoglycaemia). - d) Treated with insulin for more than 5 years. - e) Episode of hypoglycaemia (defined by symptoms of hypoglycaemia and/or episode with low glucose measurement (equal to or below 70 mg/dL \[equal to or below 3.9 mmol/L\])) within the last 12 weeks prior to Visit 1 (screening). - Subjects diagnosed (clinically) with type 2 diabetes mellitus. - Treated with basal only insulin (once daily or twice-daily insulin (insulin detemir; insulin glargine 100 U/mL, biosimilar of insulin glargine 100 U/mL or insulin Neutral Protamine Hagedorn)) equal to or above 90 days prior to the day of screening with or without any of the following anti-diabetic drugs with stable doses for equal to or above 90 days prior to screening: - a) Metformin - b) Dipeptidyl peptidase -4 inhibitor - c) Sodium-glucose co-transporter 2 inhibitor - d) Alpha-glucosidase-inhibitors (acarbose) - e) Thiazolidinediones - f) Marketed oral combination products only including the products listed in criteria 5a-5e - HbA1c equal to or below 9.5% (80 mmol/mol) at screening by central laboratory analysis. - BMI equal to or below 45 kg/m\^2.
Exclusion criteria
- 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes During Maintenance 2 (36 Weeks) | 36 Weeks | Severe or BG confirmed symptomatic hypoglycaemia was evaluated during maintenance 2 (36 weeks) period. Severe or BG confirmed symptomatic hypoglycaemia: An episode that is severe according to the ADA 2013 classification or blood glucose (BG) confirmed by a plasma glucose value \<3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. The observed rates (number of episodes divided by patient years of exposure multiplied by 100) of severe or BG-confirmed symptomatic hypoglycaemic episodes per patient years of exposure (PYE) is presented in this endpoint results. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Nocturnal, Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes During Maintenance 2 (36 Weeks) | 36 weeks | Nocturnal severe or BG confirmed symptomatic hypoglycaemia was evaluated during maintenance 2 (36 weeks). The nocturnal period defined as the period between 00:01 and 05:59 a.m. (both inclusive). Severe or BG confirmed symptomatic hypoglycaemia: An episode that is severe according to the ADA 2013 classification or blood glucose (BG) confirmed by a plasma glucose value \<3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. The observed rates (number of episodes divided by patient years of exposure multiplied by 100) of severe or BG-confirmed symptomatic hypoglycaemic episodes per patient years of exposure (PYE) is presented in this endpoint results. |
| Number of Severe Hypoglycaemic Episodes During Maintenance 2 (36 Weeks) | 36 weeks (maintenance 2) | Severe hypoglycaemia are those episodes positively adjudicated by the event adjudication committee according to the ADA definition of a severe hypoglycaemic episode. This was evaluated for maintenance 2 period. The observed rates (number of episodes divided by patient years of exposure multiplied by 100) of severe hypoglycaemic episodes per patient years of exposure (PYE) is presented in this endpoint results. |
| Change in HbA1c From Baseline to End of Treatment (up to 88 Weeks) | Week 0, week 88 | Change in glycosylated haemoglobin (HbA1c) was evaluated from baseline to end of treatment period (week 88). |
| Change in Fasting Plasma Glucose (FPG) From Baseline to End of Treatment (up to 88 Weeks) | Week 0, week 88 | Change in fasting plasma glucose (FPG) was evaluated from baseline to end of treatment period (week 88). |
| Percentage of Participants With FPG ≤ 7.2 mmol/L (130 mg/dL) at End of Treatment (up to 88 Weeks) (Yes/no) | At 88 weeks | Participants achieving a fasting plasma glucose value of less than or equal to 7.2 mmol/L (130 mg/dL) at end of treatment (up to 88 weeks). |
| Percentage of Participants With FPG ≤ 5.0 mmol/L (90 mg/dL) at End of Treatment (up to 88 Weeks) (Yes/no) | At 88 weeks | Participants achieving a fasting plasma glucose value of less than or equal to 5.0 mmol/L (90 mg/dL) at end of treatment (up to 88 weeks). |
| Percentage of Participants With HbA1c < 7.0% (53 mmol/Mol) at End of Treatment (up to 88 Weeks) and no Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During Maintenance 2 (36 Weeks) (Yes/no) | End of Treatment (up to 88 Weeks) | Participants achieving target HbA1c of less than 7.0% at the end of treatment (88 weeks) without severe or BG-confirmed hypoglycaemia during maintenance 2 (36 weeks). |
| Basal Insulin Dose (U) at End of Treatment (up to 88 Weeks) | 88 weeks | The observed mean daily basal insulin doses was evaluated at the end of trial (88 weeks). |
| Change in Mean Pre-breakfast Self-measured Plasma Glucose Used for Titration From Baseline to End of Treatment (up to 88 Weeks) | Week 0, week 88 | Participants measured their pre-breakfast self-measured plasma glucose (SMPG) value until end of treatment (week 88). Mean pre-breakfast self-measured plasma glucose used for titration at baseline and end of treatment (up to 88 weeks) are presented. |
| Number of Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes During Treatment (up to 88 Weeks) | 88 weeks | Severe or BG confirmed symptomatic hypoglycaemia was evaluated during treatment (up to 88 weeks). Severe or BG confirmed symptomatic hypoglycaemia: An episode that is severe according to the ADA 2013 classification or blood glucose (BG) confirmed by a plasma glucose value \<3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. The observed rates (number of episodes divided by patient years of exposure multiplied by 100) of severe or BG-confirmed symptomatic hypoglycaemic episodes per patient years of exposure (PYE) is presented in this endpoint results. |
| Number of Nocturnal, Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes During Treatment (up to 88 Weeks) | 88 weeks | Nocturnal severe or BG confirmed symptomatic hypoglycaemia was evaluated at the end of trial (88 weeks). The nocturnal period defined as the period between 00:01 and 05:59 a.m. (both inclusive). Severe or BG confirmed symptomatic hypoglycaemia: An episode that is severe according to the ADA 2013 classification or blood glucose (BG) confirmed by a plasma glucose value \<3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. The observed rates (number of episodes divided by patient years of exposure multiplied by 100) of severe or BG-confirmed symptomatic hypoglycaemic episodes per patient years of exposure (PYE) is presented in this endpoint results. |
| Number of Severe Hypoglycaemic Episodes During Treatment (up to 88 Weeks) | 88 weeks | Severe hypoglycaemia are those episodes positively adjudicated by the event adjudication committee according to the ADA definition of a severe hypoglycaemic episode. This was evaluated for the total trial period (88 weeks). The observed rates (number of episodes divided by patient years of exposure multiplied by 100) of severe hypoglycaemic episodes per patient years of exposure (PYE) is presented in this endpoint results. |
| Number of Adverse Events From Randomisation to End of Maintenance Period 2 (up to 88 Weeks) | 88 weeks | The adverse events presented are treatment emergent. A treatment-emergent AE (TEAE) was defined as an event that had onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last days of randomised treatment or had onset date before the first day of exposure on randomised treatment and increased in severity during the treatment period and until 7 days after the last date of randomised treatment. Number of adverse events expressed in rates, from randomisation to end of maintenance period 2 (up to 88 weeks) is presented. Rate = number of events divided by patient years of exposure multiplied by 100. |
| Change in Body Weight From Baseline to End of Treatment (up to 88 Weeks) | Week 0, week 88 | Change in body weight, measured in kilograms, from baseline (week 0) to end of treatment (week 88). |
| Percentage of Participants With HbA1c < 7.0% (53 mmol/Mol) at End of Treatment (up to 88 Weeks) and no Nocturnal, Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes During Maintenance 2 (36 Weeks) (Yes/no) | At 88 weeks | Participants achieving target HbA1c of less than 7.0% at the end of treatment (88 weeks) without nocturnal severe or BG-confirmed hypoglycaemia during maintenance 2 (36 weeks). |
Countries
Canada, Denmark, Estonia, Germany, Greece, Hungary, Norway, Poland, Puerto Rico, Romania, Serbia, United States
Participant flow
Recruitment details
The trial was conducted at 230 sites in 11 countries as follows. Number of sites that screened and randomised participants to treatment are given in parenthesis. Canada:(9/9), Denmark: (6/6), Estonia: (5/5), Germany: (11 /11), Greece: (7/7), Hungary: (9/9), Norway: (4/4), Poland: (9/9), Romania: (5/4), Serbia: (8/8), United States: (157/153).
Pre-assignment details
The participants were previously treated with basal insulin once daily or twice daily ± oral anti-diabetic drugs excluding sulfonylureas/glinides. Pre-trial insulin was discontinued and the subjects continued their pre-trial oral anti-diabetic drugs (OADs).
Participants by arm
| Arm | Count |
|---|---|
| Insulin Degludec U200 Participants received insulin degludec 200 units/mL once daily as subcutaneous injections (in the thigh, upper arm or abdomen) ± oral anti-diabetic drugs. The daily basal insulin dose was reduced by 20% from their pre-trial dose. Insulin dose was adjusted once weekly by the investigator, based on the mean of three fasting self measured plasma glucose (SMPG) values, to reach a SMPG of 4.0-5.0 mmol/L (71-90 mg/dL). The treatment duration was up to 88 weeks divided into; a 16-week titration period, an up to 36-week maintenance period 1 (variable length) and a 36-week maintenance period 2. | 805 |
| Insulin Glargine U300 Participants received insulin glargine 300 units/mL once daily as subcutaneous injections (in the thigh, upper arm or abdomen) ± pre-trial oral anti-diabetic drugs. The dose of IGlar U300 corresponded to the pre-trial daily basal insulin dose. Insulin dose was adjusted once weekly by the investigator, based on the mean of three fasting SMPG values, to reach a SMPG of 4.0-5.0 mmol/L (71-90 mg/dL). The treatment duration was up to 88 weeks divided into; a 16-week titration period, an up to 36-week maintenance period 1 (variable length) and a 36-week maintenance period 2. | 804 |
| Total | 1,609 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Maintenance Period 1 (36 Weeks) | Death | 3 | 3 |
| Maintenance Period 1 (36 Weeks) | Lost to Follow-up | 7 | 4 |
| Maintenance Period 1 (36 Weeks) | Subject withdrawal reason not collected | 1 | 0 |
| Maintenance Period 1 (36 Weeks) | Withdrawal by Subject | 36 | 36 |
| Maintencance Period 2 (36 Weeks) | Death | 4 | 6 |
| Maintencance Period 2 (36 Weeks) | Lost to Follow-up | 3 | 6 |
| Maintencance Period 2 (36 Weeks) | Not reconsenting | 0 | 2 |
| Maintencance Period 2 (36 Weeks) | Withdrawal by Subject | 18 | 13 |
Baseline characteristics
| Characteristic | Insulin Glargine U300 | Total | Insulin Degludec U200 |
|---|---|---|---|
| Age, Continuous | 62.8 Years STANDARD_DEVIATION 10 | 62.8 Years STANDARD_DEVIATION 10 | 62.9 Years STANDARD_DEVIATION 10 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 100 Participants | 184 Participants | 84 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 704 Participants | 1425 Participants | 721 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 4 Participants | 9 Participants | 5 Participants |
| Race (NIH/OMB) Asian | 29 Participants | 54 Participants | 25 Participants |
| Race (NIH/OMB) Black or African American | 65 Participants | 143 Participants | 78 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 10 Participants | 4 Participants |
| Race (NIH/OMB) White | 699 Participants | 1392 Participants | 693 Participants |
| Sex: Female, Male Female | 368 Participants | 701 Participants | 333 Participants |
| Sex: Female, Male Male | 436 Participants | 908 Participants | 472 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 7 / 802 | 9 / 798 |
| other Total, other adverse events | 496 / 802 | 476 / 798 |
| serious Total, serious adverse events | 167 / 802 | 141 / 798 |
Outcome results
Primary
Number of Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes During Maintenance 2 (36 Weeks)
Severe or BG confirmed symptomatic hypoglycaemia was evaluated during maintenance 2 (36 weeks) period. Severe or BG confirmed symptomatic hypoglycaemia: An episode that is severe according to the ADA 2013 classification or blood glucose (BG) confirmed by a plasma glucose value \<3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. The observed rates (number of episodes divided by patient years of exposure multiplied by 100) of severe or BG-confirmed symptomatic hypoglycaemic episodes per patient years of exposure (PYE) is presented in this endpoint results.
Time frame: 36 Weeks
Population: The safety analysis set (SAS) comprised all subjects who received at least one dose of the investigational product or comparator.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin Degludec 200 | Number of Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes During Maintenance 2 (36 Weeks) | 216.8 Episodes/(PYE*100) |
| Insulin Glargine U300 | Number of Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes During Maintenance 2 (36 Weeks) | 243.9 Episodes/(PYE*100) |
Comparison: The number of episodes is analysed using a negative binomial regression model (log link) with the logarithm of the time period in which a hypoglycaemic episode was considered treatment emergent as offset. The model includes treatment, number of OADs, region, sex and dosing time as fixed factors, and age as a covariate. Missing values are imputed through multiple imputation by treatment arm, based on a Poisson model.p-value: 0.171595% CI: [0.73, 1.06]Regression, Cox
Secondary
Basal Insulin Dose (U) at End of Treatment (up to 88 Weeks)
The observed mean daily basal insulin doses was evaluated at the end of trial (88 weeks).
Time frame: 88 weeks
Population: The safety analysis set (SAS) comprised all subjects who received at least one dose of the investigational product or comparator. Number Analyzed = number of participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Degludec 200 | Basal Insulin Dose (U) at End of Treatment (up to 88 Weeks) | 66.6 Units | Standard Deviation 48.54 |
| Insulin Glargine U300 | Basal Insulin Dose (U) at End of Treatment (up to 88 Weeks) | 73.0 Units | Standard Deviation 48.48 |
Secondary
Change in Body Weight From Baseline to End of Treatment (up to 88 Weeks)
Change in body weight, measured in kilograms, from baseline (week 0) to end of treatment (week 88).
Time frame: Week 0, week 88
Population: The safety analysis set (SAS) comprised all subjects who received at least one dose of the investigational product or comparator. Number Analyzed = number of participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Degludec 200 | Change in Body Weight From Baseline to End of Treatment (up to 88 Weeks) | 2.9 kg | Standard Deviation 5.17 |
| Insulin Glargine U300 | Change in Body Weight From Baseline to End of Treatment (up to 88 Weeks) | 1.7 kg | Standard Deviation 5.84 |
Secondary
Change in Fasting Plasma Glucose (FPG) From Baseline to End of Treatment (up to 88 Weeks)
Change in fasting plasma glucose (FPG) was evaluated from baseline to end of treatment period (week 88).
Time frame: Week 0, week 88
Population: Full analysis set (FAS) included all randomised subjects. Number Analyzed = number of participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Degludec 200 | Change in Fasting Plasma Glucose (FPG) From Baseline to End of Treatment (up to 88 Weeks) | -35.50 mg/dL | Standard Deviation 49.34 |
| Insulin Glargine U300 | Change in Fasting Plasma Glucose (FPG) From Baseline to End of Treatment (up to 88 Weeks) | -25.68 mg/dL | Standard Deviation 56.69 |
Secondary
Change in HbA1c From Baseline to End of Treatment (up to 88 Weeks)
Change in glycosylated haemoglobin (HbA1c) was evaluated from baseline to end of treatment period (week 88).
Time frame: Week 0, week 88
Population: The full analysis set (FAS) comprised all randomised subjects. Number Analyzed = number of participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Degludec 200 | Change in HbA1c From Baseline to End of Treatment (up to 88 Weeks) | -0.54 Percentage of HbA1c | Standard Deviation 0.91 |
| Insulin Glargine U300 | Change in HbA1c From Baseline to End of Treatment (up to 88 Weeks) | -0.46 Percentage of HbA1c | Standard Deviation 0.9 |
Secondary
Change in Mean Pre-breakfast Self-measured Plasma Glucose Used for Titration From Baseline to End of Treatment (up to 88 Weeks)
Participants measured their pre-breakfast self-measured plasma glucose (SMPG) value until end of treatment (week 88). Mean pre-breakfast self-measured plasma glucose used for titration at baseline and end of treatment (up to 88 weeks) are presented.
Time frame: Week 0, week 88
Population: Full analysis set (FAS) included all randomised subjects. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Degludec 200 | Change in Mean Pre-breakfast Self-measured Plasma Glucose Used for Titration From Baseline to End of Treatment (up to 88 Weeks) | Baseline (week 0) | 8.39 mmol/L | Standard Deviation 2.73 |
| Insulin Degludec 200 | Change in Mean Pre-breakfast Self-measured Plasma Glucose Used for Titration From Baseline to End of Treatment (up to 88 Weeks) | End of treatment (week 88) | 5.46 mmol/L | Standard Deviation 1.08 |
| Insulin Glargine U300 | Change in Mean Pre-breakfast Self-measured Plasma Glucose Used for Titration From Baseline to End of Treatment (up to 88 Weeks) | Baseline (week 0) | 8.41 mmol/L | Standard Deviation 2.75 |
| Insulin Glargine U300 | Change in Mean Pre-breakfast Self-measured Plasma Glucose Used for Titration From Baseline to End of Treatment (up to 88 Weeks) | End of treatment (week 88) | 5.56 mmol/L | Standard Deviation 1.23 |
Secondary
Number of Adverse Events From Randomisation to End of Maintenance Period 2 (up to 88 Weeks)
The adverse events presented are treatment emergent. A treatment-emergent AE (TEAE) was defined as an event that had onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last days of randomised treatment or had onset date before the first day of exposure on randomised treatment and increased in severity during the treatment period and until 7 days after the last date of randomised treatment. Number of adverse events expressed in rates, from randomisation to end of maintenance period 2 (up to 88 weeks) is presented. Rate = number of events divided by patient years of exposure multiplied by 100.
Time frame: 88 weeks
Population: The safety analysis set (SAS) comprised all subjects who received at least one dose of the investigational product or comparator.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin Degludec 200 | Number of Adverse Events From Randomisation to End of Maintenance Period 2 (up to 88 Weeks) | 367.32 Episodes/(PYE*100) |
| Insulin Glargine U300 | Number of Adverse Events From Randomisation to End of Maintenance Period 2 (up to 88 Weeks) | 365.42 Episodes/(PYE*100) |
Secondary
Number of Nocturnal, Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes During Maintenance 2 (36 Weeks)
Nocturnal severe or BG confirmed symptomatic hypoglycaemia was evaluated during maintenance 2 (36 weeks). The nocturnal period defined as the period between 00:01 and 05:59 a.m. (both inclusive). Severe or BG confirmed symptomatic hypoglycaemia: An episode that is severe according to the ADA 2013 classification or blood glucose (BG) confirmed by a plasma glucose value \<3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. The observed rates (number of episodes divided by patient years of exposure multiplied by 100) of severe or BG-confirmed symptomatic hypoglycaemic episodes per patient years of exposure (PYE) is presented in this endpoint results.
Time frame: 36 weeks
Population: The safety analysis set (SAS) comprised all subjects who received at least one dose of the investigational product or comparator. Number Analyzed = number of participants with available data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin Degludec 200 | Number of Nocturnal, Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes During Maintenance 2 (36 Weeks) | 62.30 Episodes/(PYE*100) |
| Insulin Glargine U300 | Number of Nocturnal, Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes During Maintenance 2 (36 Weeks) | 93.75 Episodes/(PYE*100) |
Secondary
Number of Nocturnal, Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes During Treatment (up to 88 Weeks)
Nocturnal severe or BG confirmed symptomatic hypoglycaemia was evaluated at the end of trial (88 weeks). The nocturnal period defined as the period between 00:01 and 05:59 a.m. (both inclusive). Severe or BG confirmed symptomatic hypoglycaemia: An episode that is severe according to the ADA 2013 classification or blood glucose (BG) confirmed by a plasma glucose value \<3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. The observed rates (number of episodes divided by patient years of exposure multiplied by 100) of severe or BG-confirmed symptomatic hypoglycaemic episodes per patient years of exposure (PYE) is presented in this endpoint results.
Time frame: 88 weeks
Population: The safety analysis set (SAS) comprised all subjects who received at least one dose of the investigational product or comparator.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin Degludec 200 | Number of Nocturnal, Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes During Treatment (up to 88 Weeks) | 36.93 Episodes/(PYE*100) |
| Insulin Glargine U300 | Number of Nocturnal, Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes During Treatment (up to 88 Weeks) | 60.03 Episodes/(PYE*100) |
Secondary
Number of Severe Hypoglycaemic Episodes During Maintenance 2 (36 Weeks)
Severe hypoglycaemia are those episodes positively adjudicated by the event adjudication committee according to the ADA definition of a severe hypoglycaemic episode. This was evaluated for maintenance 2 period. The observed rates (number of episodes divided by patient years of exposure multiplied by 100) of severe hypoglycaemic episodes per patient years of exposure (PYE) is presented in this endpoint results.
Time frame: 36 weeks (maintenance 2)
Population: The safety analysis set (SAS) comprised all subjects who received at least one dose of the investigational product or comparator. Number Analyzed = number of participants with available data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin Degludec 200 | Number of Severe Hypoglycaemic Episodes During Maintenance 2 (36 Weeks) | 0.98 Episodes/(PYE*100) |
| Insulin Glargine U300 | Number of Severe Hypoglycaemic Episodes During Maintenance 2 (36 Weeks) | 4.88 Episodes/(PYE*100) |
Secondary
Number of Severe Hypoglycaemic Episodes During Treatment (up to 88 Weeks)
Severe hypoglycaemia are those episodes positively adjudicated by the event adjudication committee according to the ADA definition of a severe hypoglycaemic episode. This was evaluated for the total trial period (88 weeks). The observed rates (number of episodes divided by patient years of exposure multiplied by 100) of severe hypoglycaemic episodes per patient years of exposure (PYE) is presented in this endpoint results.
Time frame: 88 weeks
Population: The safety analysis set (SAS) comprised all subjects who received at least one dose of the investigational product or comparator.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin Degludec 200 | Number of Severe Hypoglycaemic Episodes During Treatment (up to 88 Weeks) | 2.06 Episodes/(PYE*100) |
| Insulin Glargine U300 | Number of Severe Hypoglycaemic Episodes During Treatment (up to 88 Weeks) | 5.21 Episodes/(PYE*100) |
Secondary
Number of Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes During Treatment (up to 88 Weeks)
Severe or BG confirmed symptomatic hypoglycaemia was evaluated during treatment (up to 88 weeks). Severe or BG confirmed symptomatic hypoglycaemia: An episode that is severe according to the ADA 2013 classification or blood glucose (BG) confirmed by a plasma glucose value \<3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. The observed rates (number of episodes divided by patient years of exposure multiplied by 100) of severe or BG-confirmed symptomatic hypoglycaemic episodes per patient years of exposure (PYE) is presented in this endpoint results.
Time frame: 88 weeks
Population: The safety analysis set (SAS) comprised all subjects who received at least one dose of the investigational product or comparator.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin Degludec 200 | Number of Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes During Treatment (up to 88 Weeks) | 137.8 Episodes/(PYE*100) |
| Insulin Glargine U300 | Number of Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes During Treatment (up to 88 Weeks) | 163.7 Episodes/(PYE*100) |
Secondary
Percentage of Participants With FPG ≤ 5.0 mmol/L (90 mg/dL) at End of Treatment (up to 88 Weeks) (Yes/no)
Participants achieving a fasting plasma glucose value of less than or equal to 5.0 mmol/L (90 mg/dL) at end of treatment (up to 88 weeks).
Time frame: At 88 weeks
Population: Full analysis set (FAS) included all randomised subjects. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Insulin Degludec 200 | Percentage of Participants With FPG ≤ 5.0 mmol/L (90 mg/dL) at End of Treatment (up to 88 Weeks) (Yes/no) | Yes | 31.5 Percentage of participants |
| Insulin Degludec 200 | Percentage of Participants With FPG ≤ 5.0 mmol/L (90 mg/dL) at End of Treatment (up to 88 Weeks) (Yes/no) | No | 68.5 Percentage of participants |
| Insulin Glargine U300 | Percentage of Participants With FPG ≤ 5.0 mmol/L (90 mg/dL) at End of Treatment (up to 88 Weeks) (Yes/no) | Yes | 21.7 Percentage of participants |
| Insulin Glargine U300 | Percentage of Participants With FPG ≤ 5.0 mmol/L (90 mg/dL) at End of Treatment (up to 88 Weeks) (Yes/no) | No | 78.3 Percentage of participants |
Secondary
Percentage of Participants With FPG ≤ 7.2 mmol/L (130 mg/dL) at End of Treatment (up to 88 Weeks) (Yes/no)
Participants achieving a fasting plasma glucose value of less than or equal to 7.2 mmol/L (130 mg/dL) at end of treatment (up to 88 weeks).
Time frame: At 88 weeks
Population: Full analysis set (FAS) included all randomised subjects. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Insulin Degludec 200 | Percentage of Participants With FPG ≤ 7.2 mmol/L (130 mg/dL) at End of Treatment (up to 88 Weeks) (Yes/no) | Yes | 84.0 Percentage of participants |
| Insulin Degludec 200 | Percentage of Participants With FPG ≤ 7.2 mmol/L (130 mg/dL) at End of Treatment (up to 88 Weeks) (Yes/no) | No | 16.0 Percentage of participants |
| Insulin Glargine U300 | Percentage of Participants With FPG ≤ 7.2 mmol/L (130 mg/dL) at End of Treatment (up to 88 Weeks) (Yes/no) | Yes | 72.0 Percentage of participants |
| Insulin Glargine U300 | Percentage of Participants With FPG ≤ 7.2 mmol/L (130 mg/dL) at End of Treatment (up to 88 Weeks) (Yes/no) | No | 28.0 Percentage of participants |
Secondary
Percentage of Participants With HbA1c < 7.0% (53 mmol/Mol) at End of Treatment (up to 88 Weeks) and no Nocturnal, Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes During Maintenance 2 (36 Weeks) (Yes/no)
Participants achieving target HbA1c of less than 7.0% at the end of treatment (88 weeks) without nocturnal severe or BG-confirmed hypoglycaemia during maintenance 2 (36 weeks).
Time frame: At 88 weeks
Population: Full analysis set (FAS) included all randomised subjects. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Insulin Degludec 200 | Percentage of Participants With HbA1c < 7.0% (53 mmol/Mol) at End of Treatment (up to 88 Weeks) and no Nocturnal, Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes During Maintenance 2 (36 Weeks) (Yes/no) | Yes | 47.4 Percentage of participants |
| Insulin Degludec 200 | Percentage of Participants With HbA1c < 7.0% (53 mmol/Mol) at End of Treatment (up to 88 Weeks) and no Nocturnal, Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes During Maintenance 2 (36 Weeks) (Yes/no) | No | 52.6 Percentage of participants |
| Insulin Glargine U300 | Percentage of Participants With HbA1c < 7.0% (53 mmol/Mol) at End of Treatment (up to 88 Weeks) and no Nocturnal, Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes During Maintenance 2 (36 Weeks) (Yes/no) | Yes | 39.3 Percentage of participants |
| Insulin Glargine U300 | Percentage of Participants With HbA1c < 7.0% (53 mmol/Mol) at End of Treatment (up to 88 Weeks) and no Nocturnal, Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes During Maintenance 2 (36 Weeks) (Yes/no) | No | 60.7 Percentage of participants |
Secondary
Percentage of Participants With HbA1c < 7.0% (53 mmol/Mol) at End of Treatment (up to 88 Weeks) and no Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During Maintenance 2 (36 Weeks) (Yes/no)
Participants achieving target HbA1c of less than 7.0% at the end of treatment (88 weeks) without severe or BG-confirmed hypoglycaemia during maintenance 2 (36 weeks).
Time frame: End of Treatment (up to 88 Weeks)
Population: Full analysis set (FAS) included all randomised subjects. Number Analyzed = number of participants with available data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Insulin Degludec 200 | Percentage of Participants With HbA1c < 7.0% (53 mmol/Mol) at End of Treatment (up to 88 Weeks) and no Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During Maintenance 2 (36 Weeks) (Yes/no) | Yes | 35.3 Percentage of participants |
| Insulin Degludec 200 | Percentage of Participants With HbA1c < 7.0% (53 mmol/Mol) at End of Treatment (up to 88 Weeks) and no Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During Maintenance 2 (36 Weeks) (Yes/no) | No | 64.7 Percentage of participants |
| Insulin Glargine U300 | Percentage of Participants With HbA1c < 7.0% (53 mmol/Mol) at End of Treatment (up to 88 Weeks) and no Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During Maintenance 2 (36 Weeks) (Yes/no) | Yes | 30.0 Percentage of participants |
| Insulin Glargine U300 | Percentage of Participants With HbA1c < 7.0% (53 mmol/Mol) at End of Treatment (up to 88 Weeks) and no Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes During Maintenance 2 (36 Weeks) (Yes/no) | No | 70.0 Percentage of participants |