Diabetes, Diabetes Mellitus, Type 2
Conditions
Brief summary
This trial is conducted in Asia and Japan. The aim of this trial is to compare insulin degludec (NN1250) with insulin glargine both combined with oral antidiabetic drugs (OADs) in subjects with type 2 diabetes never treated with insulin.
Interventions
DRUGinsulin degludec
Insulin degludec injected subcutaneously (under the skin) once daily. The doses will be individually adjusted
DRUGinsulin glargine
Insulin glargine injected subcutaneously (under the skin) once daily. The doses will be 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
* For Japan only: minimum age is 20 years * Type 2 diabetes mellitus (diagnosed clinically) for at least 6 months * Current treatment with monotherapy or combination of an insulin secretagouge (sulfonylurea or glinide) and metformin, with or without addition of alfa-glucosidase-inhibitors or a DPP-4 inhibitor with unchanged dosing for at least 3 months prior to visit 1. The dose(s) should as minimum be as stated: -Insulin secretagogue (sulfonylurea or glinide): Minimum half of the daily maximal dose according to local labelling -Metformin: alone or in combination (including fixed combination): Maximum tolerated dose - alfa-glucosidase-inhibitors: Minimum half of the daily maximal dose or maximum tolerated dose -DPP-4 (dipeptyl peptidase 4) inhibitor: According to local labelling * HbA1c 7.0-10.0 % (both inclusive) by central laboratory analysis * Body Mass Index (BMI) no higher than 35.0 kg/m\^2
Exclusion criteria
* Use within the last 3 months prior to Visit 1 of: TZDs (thiazolidinediones), 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, or the intention of becoming pregnant or not using adequate contraceptive measures according to local requirements (for Thailand: adequate contraceptive measures are: diaphragm, condom (by the partner), intrauterine device in place for last three months before trial starts, sponge, cap with spermicide, contraceptive patch, approved hormonal implant (i.e. Norplant), oral contraceptives taken without difficulty for the last three months before trial starts, post menopausal state or sterilisation.) * Cancer and medical history of cancer (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 |
|---|---|---|
| Rate of Confirmed Hypoglycaemic Episodes | Week 0 to Week 26 + 7 days follow up | Rate of confirmed hypoglycaemic episodes per 100 patient years of exposure Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes are defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes are defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. |
| Rate of Nocturnal Confirmed Hypoglycaemic Episodes | Week 0 to Week 26 + 7 days follow up | Rate of nocturnal confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes are defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes are defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. Nocturnal hypoglycaemic episodes are defined as occurring between 00:01 and 05:59 a.m. |
| 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, before bedtime, at 4 am and before breakfast. |
Countries
Hong Kong, Japan, Malaysia, South Korea, Taiwan, Thailand
Participant flow
Recruitment details
The trial was conducted at 52 sites in 6 countries: Hong Kong (1), Japan (12), Malaysia (8), South Korea (19), Thailand (6) and Taiwan (6)
Pre-assignment details
Subjects continued on their current treatment with oral antidiabetic drug(s) (OAD(s) treatment except for dipeptyl peptidase-4 (DPP-4) inhibitors, at the pre-randomisation dose level and dosing frequency.
Participants by arm
| Arm | Count |
|---|---|
| IDeg OD Insulin degludec (IDeg) was given once daily (OD) subcutaneously (under the skin) in the evening in combination with pre-trial OADs (except DPP-4 inhibitors) for 26 weeks. Insulin doses were individually adjusted. | 289 |
| IGlar OD Insulin glargine (IGlar) was given once daily (OD) subcutaneously (under the skin) according to approved labelling in combination with pre-trial OADs (except DPP-4 inhibitors) for 26 weeks. Insulin doses were individually adjusted. | 146 |
| Total | 435 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 |
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Other | 12 | 3 |
| Overall Study | Protocol Violation | 3 | 2 |
| Overall Study | Withdrawal criteria | 13 | 2 |
Baseline characteristics
| Characteristic | IDeg OD | IGlar OD | Total |
|---|---|---|---|
| Age, Continuous | 58.8 years STANDARD_DEVIATION 9.8 | 58.1 years STANDARD_DEVIATION 10.1 | 58.6 years STANDARD_DEVIATION 9.9 |
| Fasting plasma glucose (FPG) | 8.4 mmol/L STANDARD_DEVIATION 2.1 | 8.6 mmol/L STANDARD_DEVIATION 1.9 | 8.5 mmol/L STANDARD_DEVIATION 2 |
| Glycosylated haemoglobin (HbA1c) | 8.4 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.8 | 8.5 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.8 | 8.5 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.8 |
| Sex: Female, Male Female | 131 Participants | 71 Participants | 202 Participants |
| Sex: Female, Male Male | 158 Participants | 75 Participants | 233 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 58 / 284 | 39 / 146 |
| serious Total, serious adverse events | 8 / 284 | 8 / 146 |
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 is imputed using last observation carried forward (LOCF).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IDeg OD | Change in Glycosylated Haemoglobin (HbA1c) | -1.24 percentage of glycosylated haemoglobin | Standard Deviation 0.87 |
| IGlar OD | Change in Glycosylated Haemoglobin (HbA1c) | -1.35 percentage of glycosylated haemoglobin | Standard Deviation 0.87 |
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, before bedtime, at 4 am and before breakfast.
Time frame: Week 26
Population: The FAS included all randomised subjects.The missing data is imputed using last observation carried forward (LOCF). For 25 subjects all 9-point SMPG values were missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IDeg OD | Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) | 8.2 mmol/L | Standard Deviation 1.8 |
| IGlar OD | Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) | 8.0 mmol/L | Standard Deviation 1.9 |
Secondary
Rate of Confirmed Hypoglycaemic Episodes
Rate of confirmed hypoglycaemic episodes per 100 patient years of exposure Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes are defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes are defined as able to treat her/himself and plasma glucose below 3.1 mmol/L.
Time frame: Week 0 to Week 26 + 7 days follow up
Population: The Safety analysis set (SAS) included all subjects who received at least one dose of the investigational product or its comparator.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IDeg OD | Rate of Confirmed Hypoglycaemic Episodes | 298 Episodes/100 years of patient exposure |
| IGlar OD | Rate of Confirmed Hypoglycaemic Episodes | 370 Episodes/100 years of patient exposure |
Secondary
Rate of Nocturnal Confirmed Hypoglycaemic Episodes
Rate of nocturnal confirmed hypoglycaemic episodes per 100 patient years of exposure (PYE). Confirmed hypoglycaemic episodes consisted of severe hypoglycaemia as well as minor hypoglycaemic episodes. Severe hypoglycaemic episodes are defined as requiring assistance to administer carbohydrate, glucagon, or other resuscitative actions. Minor hypoglycaemic episodes are defined as able to treat her/himself and plasma glucose below 3.1 mmol/L. Nocturnal hypoglycaemic episodes are defined as occurring between 00:01 and 05:59 a.m.
Time frame: Week 0 to Week 26 + 7 days follow up
Population: The Safety analysis set included all subjects who received at least one dose of the investigational product or its comparator.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IDeg OD | Rate of Nocturnal Confirmed Hypoglycaemic Episodes | 78 Episodes/100 years of patient exposure |
| IGlar OD | Rate of Nocturnal Confirmed Hypoglycaemic Episodes | 124 Episodes/100 years of patient exposure |