Type 2 Diabetes Mellitus
Conditions
Keywords
Glargine, Type 2 diabetes, Basal insulin
Brief summary
To compare the efficacy and safety of once-nightly insulin glargine versus twice-daily NPH insulin in ethnic minority type 2 diabetic patients inadequately treated with once-nightly NPH insulin alone.
Detailed description
Insulin glargine has a longer action than compared to NPH insulin, but whether this results in improved control when compared to twice-daily NPH insulin is not known when used in low-income ethnic minority patients. This study investigates whether insulin glargine may be more or less effective and safe than twice-daily NPH insulin in this population.
Interventions
DRUGInsulin glargine at bedtime instead of NPH
Insulin glargine at bedtime substituting for NPH insulin at bedtime
DRUGNPH twice-daily
Addition of morning NPH to bedtime NPH
Sponsors
National Center for Research Resources (NCRR)
Charles Drew University of Medicine and Science
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Male or female, age 18-75 * Type 2 diabetes diagnosed for at least 1 year * Inadequate glycemic control (hemoglobin A1c ≥ 7.5%) on stable and maximum-tolerated doses of a sulfonylurea, metformin and a thiazolidinedione, plus a single bedtime injection of NPH insulin * Except for the subject's current bedtime NPH insulin, no other past history of chronic insulin use (other than treatment of gestational diabetes or hospitalizations of less than 1 week in duration) * Average fasting plasma glucose level \<130 mg/dL without fasting hypoglycemia * Hemoglobin A1c between 7.5% and 12% * Body mass index (BMI) between 20 and 40 kg/m2
Exclusion criteria
* History of confirmed (or clinical suspicion of ) type 1 diabetes * Female subjects of childbearing potential who are sexually active and not using a reliable form of contraception. * Current pregnancy or lactation. * Subjects for whom intensive insulin therapy is contraindicated * Subjects with advanced proliferative diabetic retinopathy * Subjects who are unable to stay on a consistent daily meal schedule * History of any clinically significant renal, hepatic, cardiovascular, neurological, endocrinological or other major systemic disease that, in the opinion of the investigator, may make implementation of the protocol or interpretation of the data difficult. * Subjects who will likely require or initiate therapy with drugs which may interfere with glucose metabolism during the course of the study * Subjects who are in another investigational study or have received another investigational medication within 30 days of study entry * Subjects who are unable or unwilling to comply with all components of the study protocol, including contacting the investigators at specified times and attending all scheduled follow-up visits.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Hemoglobin A1c Change From Baseline | Baseline to 6 months |
Secondary
| Measure | Time frame |
|---|---|
| Frequency of Pre-supper Glucose Readings 130 mg/dL or Less, Change From Baseline | 6 months |
| Frequency of Total Hypoglycemic Reactions | 6 months |
| Any Adverse Event Other Than Hypoglycemia | 6 months |
| Body Mass Index Change From Baseline | Baseline and 6 months |
| Total Daily Insulin Dose | Baseline and 6 months |
| Frequency of Severe Hypoglycemic Reactions | 6 months |
Countries
United States
Participant flow
Recruitment details
Recruitment from Feb 2003 to Dec 2008. Subjects recruited from a diabetes specialty referral clinic, as well as from primary care clinics and through advertising in the South Los Angeles area.
Pre-assignment details
Baseline run-in period to document baseline control and reinforce dietary/lifestyle principles. 3 subjects not randomized due to protocol violations.
Participants by arm
| Arm | Count |
|---|---|
| Insulin Glargine at Bedtime Bedtime insulin glargine titrated to morning fasting glucose readings | 11 |
| NPH Twice-daily Morning and bedtime NPH insulin titrated to pre-supper and fasting glucose readings, respectively | 13 |
| Total | 24 |
Baseline characteristics
| Characteristic | NPH Twice-daily | Total | Insulin Glargine at Bedtime |
|---|---|---|---|
| Age, Continuous | 54.6 years STANDARD_DEVIATION 7.6 | 55.0 years STANDARD_DEVIATION 7.2 | 55.6 years STANDARD_DEVIATION 7 |
| Body Mass Index | 33.5 kg/m^2 STANDARD_DEVIATION 6.6 | 31.8 kg/m^2 STANDARD_DEVIATION 5.8 | 29.9 kg/m^2 STANDARD_DEVIATION 4.1 |
| Diabetes Duration | 11.5 Years STANDARD_DEVIATION 4 | 10.6 Years STANDARD_DEVIATION 3.8 | 9.4 Years STANDARD_DEVIATION 3.5 |
| Fasting Plasma Glucose | 145 mg/dL STANDARD_DEVIATION 34 | 146 mg/dL STANDARD_DEVIATION 56 | 146 mg/dL STANDARD_DEVIATION 75 |
| Hemoglobin A1c | 9.5 Percent STANDARD_DEVIATION 1.2 | 9.3 Percent STANDARD_DEVIATION 1.3 | 9.1 Percent STANDARD_DEVIATION 1.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 6 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 18 Participants | 9 Participants |
| Sex: Female, Male Female | 10 Participants | 18 Participants | 8 Participants |
| Sex: Female, Male Male | 3 Participants | 6 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 13 |
| other Total, other adverse events | 8 / 11 | 5 / 13 |
| serious Total, serious adverse events | 0 / 11 | 0 / 13 |
Outcome results
Primary
Hemoglobin A1c Change From Baseline
Time frame: Baseline to 6 months
Population: ITT (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Glargine at Bedtime | Hemoglobin A1c Change From Baseline | -0.8 Percent glycated hemoglobin | Standard Deviation 0.9 |
| NPH Twice-daily | Hemoglobin A1c Change From Baseline | -1.0 Percent glycated hemoglobin | Standard Deviation 1.2 |
Secondary
Any Adverse Event Other Than Hypoglycemia
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin Glargine at Bedtime | Any Adverse Event Other Than Hypoglycemia | 2 Events |
| NPH Twice-daily | Any Adverse Event Other Than Hypoglycemia | 1 Events |
Secondary
Body Mass Index Change From Baseline
Time frame: Baseline and 6 months
Population: ITT (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Glargine at Bedtime | Body Mass Index Change From Baseline | 0.2 kg/m^2 | Standard Deviation 1 |
| NPH Twice-daily | Body Mass Index Change From Baseline | 0.3 kg/m^2 | Standard Deviation 1.2 |
Secondary
Frequency of Pre-supper Glucose Readings 130 mg/dL or Less, Change From Baseline
Time frame: 6 months
Population: ITT (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Glargine at Bedtime | Frequency of Pre-supper Glucose Readings 130 mg/dL or Less, Change From Baseline | 38.0 % of readings, change from baseline | Standard Deviation 30.1 |
| NPH Twice-daily | Frequency of Pre-supper Glucose Readings 130 mg/dL or Less, Change From Baseline | 7.5 % of readings, change from baseline | Standard Deviation 22.6 |
Secondary
Frequency of Severe Hypoglycemic Reactions
Time frame: 6 months
Population: ITT (LOCF)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin Glargine at Bedtime | Frequency of Severe Hypoglycemic Reactions | 0 Events |
| NPH Twice-daily | Frequency of Severe Hypoglycemic Reactions | 0 Events |
Secondary
Frequency of Total Hypoglycemic Reactions
Time frame: 6 months
Population: ITT (LOCF)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin Glargine at Bedtime | Frequency of Total Hypoglycemic Reactions | 55 Events |
| NPH Twice-daily | Frequency of Total Hypoglycemic Reactions | 28 Events |
Secondary
Total Daily Insulin Dose
Time frame: Baseline and 6 months
Population: ITT (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Glargine at Bedtime | Total Daily Insulin Dose | -0.1 Units per day, change from baseline | Standard Deviation 14.4 |
| NPH Twice-daily | Total Daily Insulin Dose | 20.5 Units per day, change from baseline | Standard Deviation 9.8 |