Diabetes, Diabetes Mellitus, Type 2
Conditions
Brief summary
This trial is conducted in the United States of America. The aim of this trial is to explore how different fasting blood glucose targets affect glucose control in patients with type 2 diabetes, when patients are empowered to do dose adjustments themselves.
Interventions
DRUGinsulin detemir
Treat-to-target dose titration scheme, s.c. injection, once daily. Fasting plasma glucose (FPG) titration target range of 70-90 mg/dL
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 * 1-3 oral treatments * Insulin naive * BMI (Body Mass Index) less than or equal to 45
Exclusion criteria
* Pregnancy * Retinopathy * Cardiac disease * Uncontrolled hypertension * Recurrent hypoglycaemia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Glycosylated Haemoglobin A1c (HbA1c) Less Than 7% | week 20 | Percentage (%) of subjects reaching glycosylated haemoglobin A1c (HbA1c) less than 7% measured after 20 weeks of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Glycosylated Haemoglobin A1c (HbA1c) Less Than or Equal to 6.5% | week 20 | Percentage (%) of participants reaching glycosylated haemoglobin A1c (HbA1c) less than or equal to 6.5% measured after 20 weeks of treatment |
| Change in Glycosylated Haemoglobin A1c (HbA1c) Percentage From Baseline | week -2, week 20 | Change in glycosylated haemoglobin A1c (HbA1c) percentage from baseline measured from week -2 to week 20 |
| Incidence of Hypoglycaemic Episodes (All, Major, Minor and Symptoms Only) | weeks 0-20 | Incidence of hypoglycaemic episodes (all, major, minor and symptoms only) occurring during the treatment period from week 0 to week 20. Classification was as follows: * If subject was unable to treat himself: Major incidence. * If subject could treat himself and plasma glucose was less than 3.1 mmol/l: Minor incidence. * If subject could treat himself and plasma glucose was equal to or greater than 3.1 mmol/l, or there was no plasma glucose measurement: Symptoms only. |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
69 sites in the United States of America (USA).
Pre-assignment details
Subjects were randomised 1:1 to 2 FPG (fasting plasma glucose) titration targets. Insulin doses were self-titrated every three days based on self-measured FPG levels as follows: -3 units if FPG was below the lower limit of the target range, no change if FPG was within target range, and +3 units if FPG was above the upper limit of the target range.
Participants by arm
| Arm | Count |
|---|---|
| FPG 70-90 mg/dL Aggressive FPG (fasting plasma glucose) titration target range group | 122 |
| FPG 80-110 mg/dL Conventional FPG (fasting plasma glucose) titration target range group | 122 |
| Total | 244 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 |
| Overall Study | Discontinued due to injection | 0 | 2 |
| Overall Study | Inclusion criteria were not met | 1 | 0 |
| Overall Study | Lack of time and intolerance to drug | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Move to another state | 1 | 0 |
| Overall Study | No need of study drug to treat diabetes | 0 | 1 |
| Overall Study | No wish to keep taking Avandia | 0 | 1 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Protocol Violation | 8 | 4 |
| Overall Study | Subject off study drug for too long | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 3 |
Baseline characteristics
| Characteristic | FPG 80-110 mg/dL | Total | FPG 70-90 mg/dL |
|---|---|---|---|
| Age, Continuous | 57.2 years STANDARD_DEVIATION 10.6 | 56.9 years STANDARD_DEVIATION 10 | 56.6 years STANDARD_DEVIATION 9.4 |
| Fasting plasma glucose (FPG) | 163.1 mg/dL STANDARD_DEVIATION 40.4 | 163.5 mg/dL STANDARD_DEVIATION 41.7 | 164.0 mg/dL STANDARD_DEVIATION 43.1 |
| Glycosylated haemoglobin (HbA1c) | 7.9 percentage STANDARD_DEVIATION 0.6 | 8.0 percentage STANDARD_DEVIATION 0.6 | 8.0 percentage STANDARD_DEVIATION 0.6 |
| Sex: Female, Male Female | 44 Participants | 98 Participants | 54 Participants |
| Sex: Female, Male Male | 78 Participants | 146 Participants | 68 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 45 / 121 | 30 / 122 |
| serious Total, serious adverse events | 5 / 121 | 4 / 122 |
Outcome results
Primary
Percentage of Participants Achieving Glycosylated Haemoglobin A1c (HbA1c) Less Than 7%
Percentage (%) of subjects reaching glycosylated haemoglobin A1c (HbA1c) less than 7% measured after 20 weeks of treatment
Time frame: week 20
Population: The intent-to-treat (ITT) population with non-missing HbA1c values at end of study, LOCF (last observation carried forward)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FPG 70-90 mg/dL | Percentage of Participants Achieving Glycosylated Haemoglobin A1c (HbA1c) Less Than 7% | 64.3 percentage of participants |
| FPG 80-110 mg/dL | Percentage of Participants Achieving Glycosylated Haemoglobin A1c (HbA1c) Less Than 7% | 54.5 percentage of participants |
Comparison: To show non-inferiority for the primary endpoint, 100 subjects per group provides 80% power to show that the 95% CI for the difference of proportions between treatments is within the 20% margin under the assumption of equality of proportions. It is also sufficient to show superiority under the assumption that the first proportion is greater than the second by at least 20%. With a predicted withdrawal rate of 15%, 236 subjects were needed based on a treatment ratio of 1:1 for the two treatments.p-value: 0.041195% CI: [1.03, 3.37]Test for Difference in Proportions
Secondary
Change in Glycosylated Haemoglobin A1c (HbA1c) Percentage From Baseline
Change in glycosylated haemoglobin A1c (HbA1c) percentage from baseline measured from week -2 to week 20
Time frame: week -2, week 20
Population: The intent-to-treat (ITT), LOCF (last observation carried forward) population. One Subject in 70-90 group, however, had a missing baseline value, therefore, no change from baseline could be calculated.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FPG 70-90 mg/dL | Change in Glycosylated Haemoglobin A1c (HbA1c) Percentage From Baseline | -1.229 percentage point change | Standard Error 0.061 |
| FPG 80-110 mg/dL | Change in Glycosylated Haemoglobin A1c (HbA1c) Percentage From Baseline | -0.958 percentage point change | Standard Error 0.061 |
p-value: 0.001995% CI: [-0.441, -0.101]ANCOVA
Secondary
Incidence of Hypoglycaemic Episodes (All, Major, Minor and Symptoms Only)
Incidence of hypoglycaemic episodes (all, major, minor and symptoms only) occurring during the treatment period from week 0 to week 20. Classification was as follows: * If subject was unable to treat himself: Major incidence. * If subject could treat himself and plasma glucose was less than 3.1 mmol/l: Minor incidence. * If subject could treat himself and plasma glucose was equal to or greater than 3.1 mmol/l, or there was no plasma glucose measurement: Symptoms only.
Time frame: weeks 0-20
Population: The safety population consists of all subjects exposed to study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FPG 70-90 mg/dL | Incidence of Hypoglycaemic Episodes (All, Major, Minor and Symptoms Only) | All | 333 number of events |
| FPG 70-90 mg/dL | Incidence of Hypoglycaemic Episodes (All, Major, Minor and Symptoms Only) | Minor | 225 number of events |
| FPG 70-90 mg/dL | Incidence of Hypoglycaemic Episodes (All, Major, Minor and Symptoms Only) | Major | 1 number of events |
| FPG 70-90 mg/dL | Incidence of Hypoglycaemic Episodes (All, Major, Minor and Symptoms Only) | Symptoms only | 107 number of events |
| FPG 80-110 mg/dL | Incidence of Hypoglycaemic Episodes (All, Major, Minor and Symptoms Only) | Major | 0 number of events |
| FPG 80-110 mg/dL | Incidence of Hypoglycaemic Episodes (All, Major, Minor and Symptoms Only) | All | 227 number of events |
| FPG 80-110 mg/dL | Incidence of Hypoglycaemic Episodes (All, Major, Minor and Symptoms Only) | Symptoms only | 91 number of events |
| FPG 80-110 mg/dL | Incidence of Hypoglycaemic Episodes (All, Major, Minor and Symptoms Only) | Minor | 136 number of events |
Secondary
Percentage of Participants Achieving Glycosylated Haemoglobin A1c (HbA1c) Less Than or Equal to 6.5%
Percentage (%) of participants reaching glycosylated haemoglobin A1c (HbA1c) less than or equal to 6.5% measured after 20 weeks of treatment
Time frame: week 20
Population: The intent-to-treat (ITT) population with non-missing HbA1c values at end of study, LOCF (last observation carried forward)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FPG 70-90 mg/dL | Percentage of Participants Achieving Glycosylated Haemoglobin A1c (HbA1c) Less Than or Equal to 6.5% | 41.1 percentage of participants |
| FPG 80-110 mg/dL | Percentage of Participants Achieving Glycosylated Haemoglobin A1c (HbA1c) Less Than or Equal to 6.5% | 26.8 percentage of participants |
p-value: 0.006495% CI: [1.27, 4.3]Regression, Logistic