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 a single morning injection of glargine or once-nightly NPH insulin in ethnic minority type 2 diabetic patients inadequately controlled on combination oral agents.
Detailed description
Insulin glargine has a longer action than compared to NPH insulin, but whether this results in improved control when used as a once-nightly or morning basal insulin injection in type 2 diabetic patients who are inadequately controlled on combination oral agents has been controversial. Inner city ethnic minority patients with diabetes are a particularly challenging population of diabetic patients to treat. This study investigates whether insulin glargine may be a more effective or safer first-line basal insulin than NPH in this population.
Interventions
DRUG1- Insulin glargine QHS
Insulin glargine at bedtime (dose titrated to maintain 50% of fasting glucose readings \<120 mg/dL)
DRUG2 - Insulin glargine QAM
Insulin glargine in AM (dose titrated to maintain 50% of pre-supper glucose readings \<120 mg/dL)
DRUG3 - NPH insulin QHS
NPH insulin at bedtime (dose titrated to maintain 50% of fasting glucoses \<120 mg/dL)
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 * Treatment with stable doses of oral agents (alone or in combination) for at least 2 months * Inadequate glycemic control (hemoglobin A1c ≥ 7.5%) on maximum-tolerated doses of a sulfonylurea, metformin and a thiazolidinedione * No past history of chronic insulin use (other than treatment of gestational diabetes or hospitalizations of less than 1 week in duration) * Hemoglobin A1c between 7.5% and 12% * Body mass index (BMI) between 20 and 40 kg/m2
Exclusion criteria
* Current or previous chronic use of insulin (other than for treatment of gestational diabetes) * 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 insulin therapy is contraindicated or for whom, in the opinion of the investigator, therapy with insulin is not indicated * Subjects with advanced proliferative diabetic retinopathy * Subjects who work night shifts or 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 | Description |
|---|---|---|
| Frequency of Total Hypoglycemic Reactions | 6 months | Frequency of hypoglycemic reactions without regard to time of occurrence |
| Frequency of Severe Hypoglycemic Reactions | 6 months | Frequency of severe hypoglycemic reactions, defined as those requiring the assistance of another person |
| Frequency of Glucose Readings < 130 mg/dL | 6 months | Frequency of glucose readings below the recommended pre-meal glucose target of 130 mg/dL |
| Total Daily Insulin Dose | 6 months | Total daily number of units of insulin used |
| Any Adverse Event Other Than Hypoglycemia | 6 months | Any reported adverse event that is not hypoglycemia |
| Body Mass Index Change From Baseline | 6 months | Change in body mass index from baseline BMI measurement |
Countries
United States
Participant flow
Recruitment details
Recruitment occurred from Sep 2002 to Feb 2009. 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. 23 subjects not randomized due to protocol violations, loss to follow-up, lack of need for insulin, or voluntarily.
Participants by arm
| Arm | Count |
|---|---|
| Insulin Glargine at Bedtime Bedtime insulin glargine titrated to morning fasting glucose readings | 30 |
| Insulin Glargine in AM Morning insulin glargine titrated to pre-supper glucose readings | 25 |
| NPH Insulin Bedtime NPH insulin titrated to morning fasting glucose readings | 30 |
| Total | 85 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 2 | 3 |
| Overall Study | Protocol Violation | 8 | 8 | 10 |
Baseline characteristics
| Characteristic | Insulin Glargine at Bedtime | Insulin Glargine in AM | NPH Insulin | Total |
|---|---|---|---|---|
| Age, Continuous | 50.3 years STANDARD_DEVIATION 11.2 | 53.0 years STANDARD_DEVIATION 8.6 | 53.2 years STANDARD_DEVIATION 7.7 | 52.1 years STANDARD_DEVIATION 9.3 |
| Body Mass Index | 31.6 kg/m^2 STANDARD_DEVIATION 5 | 31.1 kg/m^2 STANDARD_DEVIATION 5.2 | 32.1 kg/m^2 STANDARD_DEVIATION 6 | 31.6 kg/m^2 STANDARD_DEVIATION 5.4 |
| Diabetes Duration | 9.0 Years STANDARD_DEVIATION 5.9 | 9.5 Years STANDARD_DEVIATION 5.2 | 7.8 Years STANDARD_DEVIATION 4.2 | 8.7 Years STANDARD_DEVIATION 5.1 |
| Hemoglobin A1c | 9.2 Percent STANDARD_DEVIATION 1.3 | 9.6 Percent STANDARD_DEVIATION 1.2 | 9.3 Percent STANDARD_DEVIATION 1.6 | 9.3 Percent STANDARD_DEVIATION 1.4 |
| Race/Ethnicity, Customized Hispanic or Latino | 24 participants | 21 participants | 25 participants | 70 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 6 participants | 4 participants | 5 participants | 15 participants |
| Sex: Female, Male Female | 15 Participants | 13 Participants | 21 Participants | 49 Participants |
| Sex: Female, Male Male | 15 Participants | 12 Participants | 9 Participants | 36 Participants |
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 | 23 / 30 | 24 / 25 | 23 / 30 |
| serious Total, serious adverse events | 0 / 30 | 1 / 25 | 0 / 30 |
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 | -1.3 Percent | Standard Deviation 1.2 |
| Insulin Glargine in AM | Hemoglobin A1c Change From Baseline | -1.9 Percent | Standard Deviation 1.4 |
| NPH Insulin | Hemoglobin A1c Change From Baseline | -1.4 Percent | Standard Deviation 1.7 |
Secondary
Any Adverse Event Other Than Hypoglycemia
Any reported adverse event that is not hypoglycemia
Time frame: 6 months
Population: Enrolled subjects
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin Glargine at Bedtime | Any Adverse Event Other Than Hypoglycemia | 1 Events |
| Insulin Glargine in AM | Any Adverse Event Other Than Hypoglycemia | 2 Events |
| NPH Insulin | Any Adverse Event Other Than Hypoglycemia | 1 Events |
Secondary
Body Mass Index Change From Baseline
Change in body mass index from baseline BMI measurement
Time frame: 6 months
Population: Enrolled subjects
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Glargine at Bedtime | Body Mass Index Change From Baseline | 0.7 kg per square meter | Standard Deviation 1.6 |
| Insulin Glargine in AM | Body Mass Index Change From Baseline | 1.1 kg per square meter | Standard Deviation 1.4 |
| NPH Insulin | Body Mass Index Change From Baseline | 0.0 kg per square meter | Standard Deviation 1.5 |
Secondary
Frequency of Glucose Readings < 130 mg/dL
Frequency of glucose readings below the recommended pre-meal glucose target of 130 mg/dL
Time frame: 6 months
Population: Enrolled subjects
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Glargine at Bedtime | Frequency of Glucose Readings < 130 mg/dL | 61.7 percentage of readings | Standard Deviation 22.8 |
| Insulin Glargine in AM | Frequency of Glucose Readings < 130 mg/dL | 73.0 percentage of readings | Standard Deviation 25.1 |
| NPH Insulin | Frequency of Glucose Readings < 130 mg/dL | 72.6 percentage of readings | Standard Deviation 22.7 |
Secondary
Frequency of Severe Hypoglycemic Reactions
Frequency of severe hypoglycemic reactions, defined as those requiring the assistance of another person
Time frame: 6 months
Population: Enrolled subjects
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin Glargine at Bedtime | Frequency of Severe Hypoglycemic Reactions | 0 Severe hypoglycemic events |
| Insulin Glargine in AM | Frequency of Severe Hypoglycemic Reactions | 0 Severe hypoglycemic events |
| NPH Insulin | Frequency of Severe Hypoglycemic Reactions | 0 Severe hypoglycemic events |
Secondary
Frequency of Total Hypoglycemic Reactions
Frequency of hypoglycemic reactions without regard to time of occurrence
Time frame: 6 months
Population: Enrolled subjects
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Glargine at Bedtime | Frequency of Total Hypoglycemic Reactions | 6.7 Hypoglycemic events per patient | Standard Deviation 9.6 |
| Insulin Glargine in AM | Frequency of Total Hypoglycemic Reactions | 9.6 Hypoglycemic events per patient | Standard Deviation 6.6 |
| NPH Insulin | Frequency of Total Hypoglycemic Reactions | 8.2 Hypoglycemic events per patient | Standard Deviation 8.7 |
Secondary
Total Daily Insulin Dose
Total daily number of units of insulin used
Time frame: 6 months
Population: Enrolled subjects
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Glargine at Bedtime | Total Daily Insulin Dose | 17.7 Units of insulin per day | Standard Deviation 10.1 |
| Insulin Glargine in AM | Total Daily Insulin Dose | 17.9 Units of insulin per day | Standard Deviation 14.4 |
| NPH Insulin | Total Daily Insulin Dose | 14.6 Units of insulin per day | Standard Deviation 13.4 |