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 the trial is to compare the efficacy and safety of two different titration algorithms for insulin degludec/insulin aspart (IDeg/IAsp) in subjects with type 2 diabetes mellitus previously treated with insulin glargine.
Interventions
DRUGinsulin degludec/insulin aspart
Twice weekly self-titration at intervals of 3-4 days, based upon a single pre-breakfast and pre-dinner SMPG (self-measured plasma glucose) value. For subcutaneous (s.c., under the skin) administration.
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 (diagnosed clinically) for at least 24 weeks prior to Visit 2 (randomisation) * Currently treated with IGlar (Insulin Glargine) and up to 3 oral antidiabetic drugs (OADs) (metformin, DPP-4 inhibitor, sulphonylurea/glinide or alpha-glucosidase inhibitor). All antidiabetic treatments should have been ongoing for at least 12 weeks prior to Visit 2 (randomisation) and doses should have been stable in this period of time * Glycosylated haemoglobin (HbA1c) 7.0-10.0% (both inclusive) by central laboratory analysis * Body mass index (BMI) below or equal to 40 kg/m\^2
Exclusion criteria
* Treatment with glucagon-like peptide 1 (GLP-1) receptor agonists or thiazolidinediones (TZDs) both within the last 12 weeks prior to Visit 2 (randomisation) * Stroke; heart failure New York Heart Association (NYHA) class III or IV; myocardial infarction; unstable angina pectoris; or coronary arterial bypass graft or angioplasty; all within the last 24 weeks prior to Visit 2 (randomisation) * Uncontrolled or untreated severe hypertension defined as systolic blood pressure above or equal to 180 mmHg and/or diastolic blood pressure above or equal to 100 mmHg * Recurrent severe hypoglycaemia (more than 1 severe hypoglycaemic event during last 12 months) or hypoglycaemic unawareness as judged by the investigator * Life-threatening disease (e.g. cancer)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HbA1c (Glycosylated Haemoglobin) (%) | Week 0, Week 26 | Change from baseline in HbA1c after 26 weeks of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Subjects With HbA1c Below 7.0% | Week 26 | Number of subjects with HbA1c below 7% after 26 weeks of treatment. |
| Percentage of Subjects With HbA1c Below 7.0% Without Confirmed Hypoglycaemia | Week 26 | Percentage of subjects with HbA1c below 7% without confirmed hypoglycaemic episodes after 26 weeks of treatment. |
| Incidence of Treatment Emergent Adverse Events (TEAEs) | Weeks 0-28 | A Treatment Emergent Adverse Event (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 day of randomised treatment. |
| Change From Baseline in Fasting Plasma Glucose (FPG) | Week 0, Week 26 | Change from baseline in fasting plasma glucose (FPG) after 26 weeks of treatment |
| Number of Treatment Emergent Confirmed Hypoglycaemic Episodes in the Maintenance Period | From week 16 to end of trial including follow-up (week 27) | Confirmed hypoglycaemic episodes in the maintenance period (from Week 16 to the end of the trial including follow-up \[Week 27\]) consisted of episodes of severe hypoglycaemia and minor hypoglycaemic episodes. Severe hypoglycaemic episodes were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. |
| Number of Treatment Emergent Nocturnal (00:01-05:59) Confirmed Hypoglycaemic Episodes | Weeks 0-27 | Confirmed hypoglycaemic episodes consisted of episodes of severe hypoglycaemia and minor hypoglycaemic episodes. Severe hypoglycaemic episodes were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. Nocturnal hypoglycaemic episodes were defined as occurring between 00:01 and 05:59 am. |
| Number of Treatment Emergent Confirmed Hypoglycaemic Episodes | Weeks 0-27 | Confirmed hypoglycaemic episodes consisted of episodes of severe hypoglycaemia and minor hypoglycaemic episodes. Severe hypoglycaemic episodes were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. |
Countries
Algeria, Germany, Malaysia, Turkey (Türkiye), United States
Participant flow
Recruitment details
The trial was conducted in 43 sites in 5 countries: Algeria (3 sites), Germany (5 sites), Malaysia (3 sites), Turkey (3 sites), and United States (29 sites).
Pre-assignment details
While entering the treatment period the subjects discontinued insulin glargine (IGlar) and sulfonylurea (SU)/glinides (if administered) but continued treatment with up to 3 other oral antidiabetic drugs (OADs) as prescribed.
Participants by arm
| Arm | Count |
|---|---|
| IDegAsp Simple Insulin degludec/insulin aspart (IDegAsp) was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) simple titration algorithm arm, self-titration was performed twice weekly at intervals of 3-4 days and based upon a single pre-breakfast and pre-dinner self-measured plasma glucose (SMPG) value. | 136 |
| IDegAsp Step Wise IDegAsp was injected subcutaneously (s.c.) in either abdomen, upper arm (deltoid area) or thigh. A pre-filled pen injector (PDS290) was used to administer IDegAsp. During treatment period subjects were allowed to continue up to 3 (oral antidiabetic drugs) OADs, except insulin glargine, sulphonylurea and glinides. In the IDegAsp twice daily (BID) stepwise titration algorithm arm, self-titration was done once weekly based on the lowest of 3 pre-breakfast and 3 pre-dinner SMPG values (measurements on 3 consecutive days prior to titration). | 136 |
| Total | 272 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 2 |
| Overall Study | Unclassified | 18 | 15 |
Baseline characteristics
| Characteristic | IDegAsp Simple | IDegAsp Step Wise | Total |
|---|---|---|---|
| Age, Continuous | 58.8 years STANDARD_DEVIATION 9.8 | 59.1 years STANDARD_DEVIATION 9.4 | 58.9 years STANDARD_DEVIATION 9.6 |
| Fasting plasma glucose | 7.8 mmol/L STANDARD_DEVIATION 2.3 | 8.1 mmol/L STANDARD_DEVIATION 3 | 8.0 mmol/L STANDARD_DEVIATION 2.6 |
| Glycosylated Haemoglobin (HbA1c) | 8.2 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.9 | 8.2 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.9 | 8.2 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.9 |
| Sex: Female, Male Female | 60 Participants | 53 Participants | 113 Participants |
| Sex: Female, Male Male | 76 Participants | 83 Participants | 159 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 45 / 135 | 53 / 134 |
| serious Total, serious adverse events | 7 / 135 | 10 / 134 |
Outcome results
Primary
Change From Baseline in HbA1c (Glycosylated Haemoglobin) (%)
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. Missing data were imputed using last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| IDegAsp Simple | Change From Baseline in HbA1c (Glycosylated Haemoglobin) (%) | -1.45 Percent (%) glycosylated haemoglobin | Standard Error 0.09 |
| IDegAsp Step Wise | Change From Baseline in HbA1c (Glycosylated Haemoglobin) (%) | -1.33 Percent (%) glycosylated haemoglobin | Standard Error 0.09 |
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG)
Change from baseline in fasting plasma glucose (FPG) after 26 weeks of treatment
Time frame: Week 0, Week 26
Population: The full analysis set (FAS) included all randomised subjects. Missing data were imputed using LOCF.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| IDegAsp Simple | Change From Baseline in Fasting Plasma Glucose (FPG) | -1.68 mmol/L | Standard Error 0.23 |
| IDegAsp Step Wise | Change From Baseline in Fasting Plasma Glucose (FPG) | -1.98 mmol/L | Standard Error 0.23 |
Secondary
Incidence of Treatment Emergent Adverse Events (TEAEs)
A Treatment Emergent Adverse Event (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 day of randomised treatment.
Time frame: Weeks 0-28
Population: The safety analysis set included all subjects who received at least one dose of the investigational product.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IDegAsp Simple | Incidence of Treatment Emergent Adverse Events (TEAEs) | 242 number of events |
| IDegAsp Step Wise | Incidence of Treatment Emergent Adverse Events (TEAEs) | 286 number of events |
Secondary
Number of Treatment Emergent Confirmed Hypoglycaemic Episodes
Confirmed hypoglycaemic episodes consisted of episodes of severe hypoglycaemia and minor hypoglycaemic episodes. Severe hypoglycaemic episodes were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L.
Time frame: Weeks 0-27
Population: The safety analysis set included all subjects who received at least one dose of the investigational product.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IDegAsp Simple | Number of Treatment Emergent Confirmed Hypoglycaemic Episodes | 552 episodes |
| IDegAsp Step Wise | Number of Treatment Emergent Confirmed Hypoglycaemic Episodes | 323 episodes |
Secondary
Number of Treatment Emergent Confirmed Hypoglycaemic Episodes in the Maintenance Period
Confirmed hypoglycaemic episodes in the maintenance period (from Week 16 to the end of the trial including follow-up \[Week 27\]) consisted of episodes of severe hypoglycaemia and minor hypoglycaemic episodes. Severe hypoglycaemic episodes were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L.
Time frame: From week 16 to end of trial including follow-up (week 27)
Population: The safety analysis set included all subjects who received at least one dose of the investigational product. Subjects in maintenance period were included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IDegAsp Simple | Number of Treatment Emergent Confirmed Hypoglycaemic Episodes in the Maintenance Period | 230 episodes |
| IDegAsp Step Wise | Number of Treatment Emergent Confirmed Hypoglycaemic Episodes in the Maintenance Period | 143 episodes |
Secondary
Number of Treatment Emergent Nocturnal (00:01-05:59) Confirmed Hypoglycaemic Episodes
Confirmed hypoglycaemic episodes consisted of episodes of severe hypoglycaemia and minor hypoglycaemic episodes. Severe hypoglycaemic episodes were defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes were defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. Nocturnal hypoglycaemic episodes were defined as occurring between 00:01 and 05:59 am.
Time frame: Weeks 0-27
Population: The safety analysis set included all subjects who received at least one dose of the investigational product.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IDegAsp Simple | Number of Treatment Emergent Nocturnal (00:01-05:59) Confirmed Hypoglycaemic Episodes | 82 episodes |
| IDegAsp Step Wise | Number of Treatment Emergent Nocturnal (00:01-05:59) Confirmed Hypoglycaemic Episodes | 49 episodes |
Secondary
Percentage of Subjects With HbA1c Below 7.0% Without Confirmed Hypoglycaemia
Percentage of subjects with HbA1c below 7% without confirmed hypoglycaemic episodes after 26 weeks of treatment.
Time frame: Week 26
Population: The full analysis set (FAS) included all randomised subjects. Missing data were imputed using LOCF. Twenty five (25) subjects did not contribute to statistical analysis as Endpoint was only defined for subjects exposed for at least 12 treatment weeks.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IDegAsp Simple | Percentage of Subjects With HbA1c Below 7.0% Without Confirmed Hypoglycaemia | 25.4 percentage of subjects |
| IDegAsp Step Wise | Percentage of Subjects With HbA1c Below 7.0% Without Confirmed Hypoglycaemia | 32.0 percentage of subjects |
Secondary
Subjects With HbA1c Below 7.0%
Number of subjects with HbA1c below 7% after 26 weeks of treatment.
Time frame: Week 26
Population: The full analysis set (FAS) included all randomised subjects. Missing data were imputed using LOCF.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IDegAsp Simple | Subjects With HbA1c Below 7.0% | 91 Subjects |
| IDegAsp Step Wise | Subjects With HbA1c Below 7.0% | 85 Subjects |