Diabetes, Diabetes Mellitus, Type 2
Conditions
Brief summary
This trial will be conducted in Africa, Asia, North America and South America. The aim of this clinical trial is to compare NN1250 (insulin degludec) with sitagliptin, as add-on to subject's own current oral antidiabetic (OAD) treatment, in subjects with type 2 diabetes inadequately controlled with 1-2 OADs (metformin, sulphonylurea, glinides or pioglitazone).
Interventions
DRUGinsulin degludec
Injected under the skin once daily for 26 weeks. The doses will be individually adjusted.
DRUGsitagliptin
Sitagliptin tablets administered orally once a day at the same time every day for 26 weeks
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 6 months * Ongoing treatment with 1 or 2 of the following OADs (metformin, insulin secretagogue (sulphonylurea or glinides) or pioglitazone) in any combination with unchanged dosing for at least 3 months prior to Visit 1 with the minimum doses stated: -Metformin: alone or in combination (including fixed combination)1500 mg or maximum tolerated dose (at least 1000 mg daily) -Insulin secretagogue (sulfonylurea or glinide): minimum half of the maximal daily dose according to local labelling -Pioglitazone: minimum half of the maximal daily dose according to local labelling or maximum tolerated dose * Body Mass Index (BMI) below or equal to 40.0 kg/m\^2 * HbA1c 7.5-11.0 % (both inclusive) by central laboratory analysis
Exclusion criteria
* Use within the last 3 months prior to Visit 1 of: exenatide, liraglutide, rosiglitazone or acarbose * 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) * Recurrent severe hypoglycaemia (more than 1 severe hypoglycaemic event during the last 12 months) or hypoglycaemic unawareness as judged by the Investigator or hospitalisation for diabetic ketoacidosis during the previous 6 months * Pregnancy, breast-feeding, the intention of becoming pregnant or not using adequate * Cancer and medical history hereof (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 |
|---|---|---|
| Change in Fasting Plasma Glucose (FPG) | Week 0, Week 26 | Change from baseline in FPG after 26 weeks of treatment |
Countries
Argentina, Canada, India, Mexico, South Africa, Turkey (Türkiye), United States
Participant flow
Recruitment details
The trial was conducted at 78 sites in 7 countries: Argentina (2 sites), Canada (11 sites), India (8 sites), Mexico (2 sites), South Africa (3 sites), Turkey (5 sites) and the United States (47 sites).
Participants by arm
| Arm | Count |
|---|---|
| IDeg OD Insulin degludec (IDeg) was given once daily subcutaneously (s.c.) for 26 weeks with pre-trial treatment being 1 or 2 oral anti-diabetic drugs (metformin, sulfonylureas, glinides, pioglitazone) in any combination. Variation in injection time from day to day was allowed (minimum 8 hours and maximum 40 hours between injections). | 225 |
| DPP-IV Inhibitor Sitagliptin was given once daily dose of 100 mg for 26 weeks with pre-trial treatment being 1 or 2 oral anti-diabetic drugs (metformin, sulfonylureas, glinides, pioglitazone) in any combination. | 222 |
| Total | 447 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 9 | 2 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Protocol Violation | 7 | 12 |
| Overall Study | Unclassified | 36 | 35 |
| Overall Study | Withdrawal Criteria | 3 | 5 |
Baseline characteristics
| Characteristic | IDeg OD | DPP-IV Inhibitor | Total |
|---|---|---|---|
| Age, Continuous | 56.4 years STANDARD_DEVIATION 10.2 | 54.9 years STANDARD_DEVIATION 11.4 | 55.7 years STANDARD_DEVIATION 10.9 |
| Fasting plasma glucose (FPG) | 9.4 mmol/L STANDARD_DEVIATION 2.6 | 9.9 mmol/L STANDARD_DEVIATION 3.1 | 9.7 mmol/L STANDARD_DEVIATION 2.9 |
| Glycosylated haemoglobin (HbA1c) | 8.8 percentage of glycosylated haemoglobin STANDARD_DEVIATION 1 | 9.0 percentage of glycosylated haemoglobin STANDARD_DEVIATION 1 | 8.9 percentage of glycosylated haemoglobin STANDARD_DEVIATION 1 |
| Sex: Female, Male Female | 84 Participants | 101 Participants | 185 Participants |
| Sex: Female, Male Male | 141 Participants | 121 Participants | 262 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 44 / 226 | 53 / 228 |
| serious Total, serious adverse events | 14 / 226 | 10 / 228 |
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 was imputed using last observation carried forward (LOCF). A site was closed, hence 11 randomised subjects (4 subjects with IDeg; 7 subjects with DPP-IV group/arm) were excluded from the FAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IDeg OD | Change in Glycosylated Haemoglobin (HbA1c) | -1.56 percentage of glycosylated haemoglobin | Standard Deviation 1.09 |
| DPP-IV Inhibitor | Change in Glycosylated Haemoglobin (HbA1c) | -1.22 percentage of glycosylated haemoglobin | Standard Deviation 1.16 |
Secondary
Change in Fasting Plasma Glucose (FPG)
Change from baseline in FPG after 26 weeks of treatment
Time frame: Week 0, Week 26
Population: The FAS included all randomised subjects and missing data was imputed using LOCF. One site was closed, hence 11 randomised subjects (4 in IDeg and 7 in DPP-IV group/arm) were excluded from the FAS. Fasting plasma glucose values were missing for another 8 subjects, hence did not contribute to the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IDeg OD | Change in Fasting Plasma Glucose (FPG) | -3.22 mmol/L | Standard Deviation 3.17 |
| DPP-IV Inhibitor | Change in Fasting Plasma Glucose (FPG) | -1.39 mmol/L | Standard Deviation 3.11 |