Diabetes, Diabetes Mellitus, Type 2
Conditions
Brief summary
This trial is conducted in Africa, Asia, Europe and South America. The aim of this clinical trial is to compare NN1250 (insulin degludec (IDeg) with insulin glargine (IGlar) in patients with type 2 diabetes. Subjects treated with oral antidiabetic drug(s) (OAD(s)) should continue their current OAD treatment at the stable, prerandomisation dose level and dosing frequency.
Interventions
DRUGinsulin degludec
Injected s.c. (under the skin) once daily (alternative regimen). Dose was individually adjusted.
DRUGinsulin glargine
Insulin glargine injected s.c. (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 * Current treatment: oral anti-diabetic drug(s) (OAD(s)) alone, basal insulin alone or the combination of OAD(s) and basal insulin. Allowed OADs are: Metformin, insulin secretagogues (sulphonylureas (SU) or glinides), pioglitazone with unchanged dosing for at least 3 months prior to Visit 1 * HbA1c: OADs only users 7.0-11.0 % (both inclusive), basal insulin with/without OADs users 7.0-10.0% (both inclusive) by central laboratory analysis * Body Mass Index (BMI) below or equal to 40.0 kg/m\^2
Exclusion criteria
* Cancer and medical history of cancer hereof * Use within the last 3 months prior to Visit 1 of: glucagon-like peptide-1(GLP-1) receptor agonist (exenatide, liraglutide), rosiglitazone, dipeptidyl peptidase IV (DPP-IV) inhibitors, alpha-glucosidase-inhibitors * 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, 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 and 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, before bedtime, at 4 am and before breakfast. |
| 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 (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. |
| 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. |
Countries
Argentina, Finland, Hungary, India, Israel, Malaysia, Mexico, North Macedonia, Norway, Russia, Serbia, South Africa, Taiwan, United Kingdom
Participant flow
Recruitment details
The trial was conducted at 69 sites in 14 countries: Hungary (3 sites), Macedonia (1 site), Serbia (3 sites), Finland (7 sites), Norway (6 sites), United Kingdom (6 sites), Argentina (4 sites), Mexico (2 sites), South Africa (3 sites), India (10 sites), Malaysia (5 sites), Taiwan (3 sites), Russian Federation (8 sites) and Israel (8 sites).
Participants by arm
| Arm | Count |
|---|---|
| IDeg OD FF Insulin degludec (IDeg) was given once daily (OD) subcutaneously (s.c.) with or without pre-trial OADs for 26 weeks with alternating morning and evening dosing according to a fixed flexible (FF) schedule (approximately 8-40 hours intervals between doses). | 229 |
| IDeg OD Insulin degludec (IDeg) was given once daily (OD) subcutaneously (s.c.) at main evening meal with or without pre-trial OADs for 26 weeks. | 228 |
| IGlar OD Insulin glargine (IGlar) was given once daily (OD) subcutaneously (s.c.) according to local labelling with or without pre-trial OADs for 26 weeks. | 230 |
| Total | 687 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 | 2 |
| Overall Study | Lack of Efficacy | 2 | 2 | 1 |
| Overall Study | Other | 14 | 14 | 17 |
| Overall Study | Protocol Violation | 3 | 3 | 3 |
| Overall Study | Withdrawal criteria | 5 | 4 | 4 |
Baseline characteristics
| Characteristic | IDeg OD FF | IDeg OD | IGlar OD | Total |
|---|---|---|---|---|
| Age, Continuous | 56.2 years STANDARD_DEVIATION 10.3 | 56.5 years STANDARD_DEVIATION 9.6 | 56.7 years STANDARD_DEVIATION 8.8 | 56.4 years STANDARD_DEVIATION 9.6 |
| Fasting plasma glucose (FPG) | 9.0 mmol/L STANDARD_DEVIATION 2.6 | 8.8 mmol/L STANDARD_DEVIATION 2.8 | 9.0 mmol/L STANDARD_DEVIATION 2.8 | 8.9 mmol/L STANDARD_DEVIATION 2.7 |
| Gender Female | 94 Participants | 104 Participants | 119 Participants | 317 Participants |
| Gender Male | 135 Participants | 124 Participants | 111 Participants | 370 Participants |
| Glycosylated haemoglobin (HbA1c) | 8.5 percentage of glycosylated haemoglobin STANDARD_DEVIATION 1 | 8.4 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.9 | 8.4 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.9 | 8.4 percentage of glycosylated haemoglobin STANDARD_DEVIATION 0.9 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 58 / 230 | 57 / 226 | 53 / 229 |
| serious Total, serious adverse events | 6 / 230 | 8 / 226 | 4 / 229 |
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). In FAS, subjects contributed to the evaluation 'as randomised'.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IDeg OD FF | Change in Glycosylated Haemoglobin (HbA1c) | -1.28 percentage of glycosylated haemoglobin | Standard Deviation 1 |
| IDeg OD | Change in Glycosylated Haemoglobin (HbA1c) | -1.07 percentage of glycosylated haemoglobin | Standard Deviation 0.99 |
| IGlar OD | Change in Glycosylated Haemoglobin (HbA1c) | -1.26 percentage of glycosylated haemoglobin | Standard Deviation 1.07 |
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 and missing data is imputed using last observation carried forward (LOCF). In FAS, subjects contributed to the evaluation 'as randomised'. For 28 subjects all 9-point SMPG values were missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IDeg OD FF | Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) | 7.9 mmol/L | Standard Deviation 1.8 |
| IDeg OD | Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) | 8.0 mmol/L | Standard Deviation 2.1 |
| IGlar OD | Mean of 9-point Self Measured Plasma Glucose Profile (SMPG) | 7.8 mmol/L | Standard Deviation 1.9 |
Secondary
Rate of Confirmed Hypoglycaemic Episodes
Rate of 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.
Time frame: Week 0 to Week 26 + 7 days follow up
Population: The SAS included all subjects who received at least one dose of the investigational product or its comparator. In SAS, subjects contributed to the evaluation 'as treated'.230 subjects in the IDeg Flex group, 226 in the IDeg OD group and 229 in the IGlar OD group
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IDeg OD FF | Rate of Confirmed Hypoglycaemic Episodes | 364 Episodes/100 years of patient exposure |
| IDeg OD | Rate of Confirmed Hypoglycaemic Episodes | 363 Episodes/100 years of patient exposure |
| IGlar OD | Rate of Confirmed Hypoglycaemic Episodes | 348 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 SAS included all subjects who received at least one dose of the investigational product or its comparator. In SAS, subjects contributed to the evaluation 'as treated'.230 subjects in the IDeg Flex group, 226 in the IDeg OD group and 229 in the IGlar OD group
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IDeg OD FF | Rate of Nocturnal Confirmed Hypoglycaemic Episodes | 63 Episodes/100 years of patient exposure |
| IDeg OD | Rate of Nocturnal Confirmed Hypoglycaemic Episodes | 56 Episodes/100 years of patient exposure |
| IGlar OD | Rate of Nocturnal Confirmed Hypoglycaemic Episodes | 75 Episodes/100 years of patient exposure |