Diabetes Mellitus, Type 1, Type 1 Diabetes
Conditions
Keywords
Type 1 Diabetes, Insulin Glargine, Human Insulin, Insulin Analogue, Bangladesh, Tanzania
Brief summary
The primary objective of this trial is to determine whether insulin glargine reduces the risk of serious hypoglycemia or improves Time in Range at 6 months when compared against standard of care human insulin (e.g. NPH or premixed 70/30) among youth living with type 1 diabetes (T1D) in low resource settings.
Detailed description
Long-acting insulin analogues have become a de-facto standard of care for patients with T1D living in high-income countries. Unfortunately, insulin analogues remain unavailable or unaffordable for much of the global population. In both 2017 and 2019, applications to add long-acting insulin analogues to the WHO's Model List of Essential Medicines (EML) were rejected due to insufficient evidence of superiority and an unfavorable cost-effectiveness profile when compared against older, less expensive, human insulins (e.g., NPH insulin and premixed 70/30 insulin). In 2021, long-acting insulin analogues were added to the EML but the decision remains controversial since the WHO concluded that magnitude of clinical benefit of long-acting insulin analogues over human insulin for most clinical outcomes was small. Moreover, studies that compare long-acting insulin analogues versus human insulins conducted in high-income settings may not generalize to children and young adults living with T1D in very low-resource settings. To address this unmet need, Pitt has partnered with Brigham and Women's Hospital, The London School of Hygiene and Tropical Medicine, the Clinton Health Access Initiative and Life For a Child to conduct a randomized controlled trial comparing insulin glargine, a long-acting analogue insulin, against intermediate human insulin among 400 children and young adults living with T1D in a lower resource setting. Note: In preparation for results submission, we made minor changes to the outcomes sections to reflect what is listed in the protocol. For Primary Outcomes #1 and #2, and Secondary Outcomes #3,#4, #5, #7, #8: we added 12 months measurements (in addition to the 6 months measurement). We updated Secondary Outcome #9 to specify the PedsQL Diabetes Symptoms Score. We added Secondary Outcome #10 to include the PedsQL Diabetes Management Score. We added Secondary Outcome #11 for ITSQ scores.
Interventions
DRUGInsulin Glargine
Formulation: Available as a clear liquid in a glass cartridge (1 cartridge =3ml=300 units). Route: Reusable pen Amount of each dose: varies depending on baseline basal insulin needs Dose escalation scheme: Participants randomly assigned to glargine will start with a dose that is generally equal to 80% of their total basal human insulin dose prior to the switch (per ISPAD guidelines and the switching guide developed by Life for a Child with the guidance of Dr. Ragnar Hanas and two other ISPAD members familiar with less-resourced settings). Frequency of dose: once per day (usually administered before bedtime) Duration of therapy: 12 months
DRUGNPH or premixed 70/30 (human insulin)
Formulation: Available as a liquid in a glass cartridge (3ml=300IU) or as liquid in a prefilled, disposable pen (3ml=300IU). Route: Bangladesh = reusable pens; Tanzania = disposable pens Amount of each dose: varies depending on baseline basal insulin needs (per usual care or treating clinician) Frequency of dose: once or twice per day (per usual care or treating clinician) Duration of therapy: 12 months
Sponsors
The Leona M. and Harry B. Helmsley Charitable Trust
Jing Luo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
7 Years to 25 Years
Healthy volunteers
No
Inclusion criteria
1. Children and young adults (age 7-25) 2. Have a clinical diagnosis of type 1 diabetes (T1D)
Exclusion criteria
1. Prior use of any insulin analogue 2. Patients (or parents for children \<18 years old) who refuse to or cannot provide informed consent 3. Who are currently pregnant or plan to become pregnant over the next year 4. Who have previously used a continuous glucose monitor (CGM) for glucose monitoring 5. Who were first diagnosed with T1D less than 12 months ago 6. Who is diagnosed with severe malnutrition
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time-in-serious Hypoglycemia | 6 and 12 months after randomization | % time spent less than 54 mg/dl averaged across all daily measures. For 6-month outcome, these data were averaged across two CGM sensors (placed at 6 and 6.5 months). For 12-month outcome, these data were from one CGM sensor placed at 11.5 months. |
| Time-in-range (TIR) | 6 and 12 months after randomization | % time spent between 70 and 180mg/dl inclusive averaged across all daily measures. For 6-month outcome, these data were averaged across two CGM sensors (placed at 6 and 6.5 months). For 12-month outcome, these data were from one CGM sensor placed at 11.5 months. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Nocturnal Hypoglycemic Events | 6 and 12 months after randomization | Number of events defined as ≥15 minutes in duration \<70 mg/dL between midnight and 6:00 am; specifically, at least 2 sensor values \<70 mg/dL that are ≥15 minutes apart plus no intervening values ≥70 mg/dL For 6-month outcome, these data were averaged across two CGM sensors (placed at 6 and 6.5 months). For 12-month outcome, these data were from one CGM sensor placed at 11.5 months. |
| Glycemic Control (HbA1c) | baseline, 3, 6, 9 and 12 months after randomization | Mean HbA1c lab result reported as percent, which is typically how it is reported. |
| Rate of Severe Hypoglycemic Events | 6 and 12 months after randomization | Severe hypoglycemic events (requiring assistance of another person to correct) reported by participant per 1000 person-years |
| Time-in-hypoglycemia | 6 and 12 months after randomization | % time spent less than 70mg/dl averaged across all daily measures. For 6-month outcome, these data were averaged across two CGM sensors (placed at 6 and 6.5 months). For 12-month outcome, these data were from one CGM sensor placed at 11.5 months. |
| Pediatric Quality of Life Inventory 3.2 Diabetes Module (PedsQL 3.2 DM) Diabetes Symptoms Score | Baseline and at 6 and 12 months after randomization | Mean PedsQL 3.2 DM Diabetes Symptoms score. PedsQL 3.2 DM Diabetes Symptoms scale is composed of 15 items. All items use the same 5-point Likert response scale, with responses ranging from never (0) to almost always (4). Items are reverse scored and transformed on a scale ranging from 0 to 100. The score is the sum of all the items over the number of items answered. Higher scores indicate fewer diabetes symptoms and therefore improved diabetes-specific health-related quality of life (D-HRQoL). |
| Pediatric Quality of Life Inventory 3.2 Diabetes Module (PedsQL 3.2 DM) Diabetes Management Score | Baseline and at 6 and 12 months after randomization | Mean PedsQL 3.2 DM Diabetes Management score. PedsQL 3.2 DM Diabetes Management scale is composed of 18 items. All items use the same 5-point Likert response scale, with responses ranging from never (0) to almost always (4). Items are reverse scored and transformed on a scale ranging from 0 to 100. Higher scores indicate fewer diabetes management problems and therefore improved D-HRQoL. |
| Insulin Treatment Satisfaction Questionnaire (ITSQ) Scores | Baseline and at 6 and 12 months after randomization | The ITSQ is composed of 22 items. A total 22-item score is reported, and the items are also divided into five subscales: Regimen Inconvenience (5 items), Lifestyle Flexibility (3 items), Glycemic Control (3 items), Hypoglycemic Control (5 items), and Insulin Delivery Device Satisfaction (6 items). Items use 7-point Likert scale responses, ranging from 1 (positive, e.g. No bother at all) to 7 (negative, e.g. A tremendous bother), though the specific response labels vary by question. Items were reverse scored and transformed to range from 0 to 100. Higher scores indicate higher treatment satisfaction. |
| Rate of Diabetic Ketoacidosis (DKA) | 6 and 12 months after randomization | Hospitalization or Emergency Room Visit (serious adverse event) with primary diagnosis of Diabetic Ketoacidosis. This was measured by self-report and confirmed through review of hospital records |
| Time-above-range | 6 and 12 months after randomization | % time spent greater than 180mg/dl averaged across all daily measures. For 6-month outcome, these data were averaged across two CGM sensors (placed at 6 and 6.5 months). For 12-month outcome, these data were from one CGM sensor placed at 11.5 months. |
Countries
Bangladesh, Tanzania
Participant flow
Pre-assignment details
17 participants consented and had baseline demographics collected in-person and/or baseline/run-in CGM placed, but withdrew from study before randomization to arm due to the following reasons: No longer interested in participating, Became ineligible
Participants by arm
| Arm | Count |
|---|---|
| Glargine Insulin glargine (long-acting insulin analogue)
Insulin Glargine: Formulation: Available as a clear liquid in a glass cartridge (1 cartridge =3ml=300 units).
Route: Reusable pen
Amount of each dose: varies depending on baseline basal insulin needs
Dose escalation scheme: Participants randomly assigned to glargine will start with a dose that is generally equal to 80% of their total basal human insulin dose prior to the switch (per ISPAD guidelines and the switching guide developed by Life for a Child with the guidance of Dr. Ragnar Hanas and two other ISPAD members familiar with less-resourced settings).
Frequency of dose: once per day (usually administered before bedtime)
Duration of therapy: 12 months | 199 |
| NPH or Premixed 70/30 (Human Insulin) NPH or premixed 70/30 (human insulin)
NPH or premixed 70/30 (human insulin): Formulation: Available as a liquid in a glass vial or glass cartridge (10ml=1000IU).
Route: Bangladesh = syringes or reusable pens; Tanzania = disposable pens
Subcutaneous injection using insulin syringe and needle
Amount of each dose: varies depending on baseline basal insulin needs (per usual care or treating clinician)
Frequency of dose: once or twice per day (per usual care or treating clinician)
Duration of therapy: 12 months | 201 |
| Total | 400 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Lost to Follow-up | 5 | 1 |
| Overall Study | Pregnancy | 5 | 2 |
Baseline characteristics
| Characteristic | Glargine | NPH or Premixed 70/30 (Human Insulin) | Total |
|---|---|---|---|
| Age, Continuous | 17.1 years STANDARD_DEVIATION 5.2 | 16.6 years STANDARD_DEVIATION 5 | 16.8 years STANDARD_DEVIATION 5.1 |
| Age, Customized Age, categorical 10 -<18 years | 84 Participants | 88 Participants | 172 Participants |
| Age, Customized Age, categorical 18 - <26 years | 89 Participants | 89 Participants | 178 Participants |
| Age, Customized Age, categorical 7 -<10 years | 26 Participants | 24 Participants | 50 Participants |
| Amputation | 0 Participants | 0 Participants | 0 Participants |
| BMI | 20.3 (kg/m^2) STANDARD_DEVIATION 4 | 19.8 (kg/m^2) STANDARD_DEVIATION 3.7 | 20.0 (kg/m^2) STANDARD_DEVIATION 3.9 |
| c-peptide | 0.25 ng/mL STANDARD_DEVIATION 0.31 | 0.25 ng/mL STANDARD_DEVIATION 0.34 | 0.25 ng/mL STANDARD_DEVIATION 0.32 |
| Diabetic Foot Disease | 2 Participants | 0 Participants | 2 Participants |
| Duration of Type 1 Diabetes | 5.9 years STANDARD_DEVIATION 4.2 | 5.9 years STANDARD_DEVIATION 3.8 | 5.9 years STANDARD_DEVIATION 4 |
| Education of Parent College/Diploma | 26 Participants | 36 Participants | 62 Participants |
| Education of Parent Don't know | 0 Participants | 2 Participants | 2 Participants |
| Education of Parent No Education | 10 Participants | 14 Participants | 24 Participants |
| Education of Parent Primary School/Education | 47 Participants | 46 Participants | 93 Participants |
| Education of Parent Secondary School/Education | 93 Participants | 77 Participants | 170 Participants |
| Education of Parent University | 23 Participants | 26 Participants | 49 Participants |
| Education of Participant College/Diploma | 44 Participants | 54 Participants | 98 Participants |
| Education of Participant No Education | 1 Participants | 3 Participants | 4 Participants |
| Education of Participant Primary School/Education | 64 Participants | 66 Participants | 130 Participants |
| Education of Participant Secondary School/Education | 76 Participants | 67 Participants | 143 Participants |
| Education of Participant University | 14 Participants | 11 Participants | 25 Participants |
| HbA1c | 9.7 percent STANDARD_DEVIATION 2.8 | 9.9 percent STANDARD_DEVIATION 2.8 | 9.8 percent STANDARD_DEVIATION 2.8 |
| History of DKA (diabetic ketoacidosis) Don't know | 0 Participants | 1 Participants | 1 Participants |
| History of DKA (diabetic ketoacidosis) No | 146 Participants | 139 Participants | 285 Participants |
| History of DKA (diabetic ketoacidosis) Yes | 53 Participants | 61 Participants | 114 Participants |
| ITSQ Total | 75.0 score on a scale STANDARD_DEVIATION 14.4 | 75.6 score on a scale STANDARD_DEVIATION 14.4 | 75.3 score on a scale STANDARD_DEVIATION 14.4 |
| Nephropathy | 2 Participants | 3 Participants | 5 Participants |
| Neuropathy | 3 Participants | 1 Participants | 4 Participants |
| Nocturnal Hypoglycemic Events | 3.6 number of events STANDARD_DEVIATION 3.4 | 3.4 number of events STANDARD_DEVIATION 3.2 | 3.5 number of events STANDARD_DEVIATION 3.3 |
| Number of Asymptomatic Hypoglycemic Events | 1.0 number of events STANDARD_DEVIATION 2.4 | 1.1 number of events STANDARD_DEVIATION 1.9 | 1.0 number of events STANDARD_DEVIATION 2.1 |
| Number of Severe Hypoglycemic Events | 0.9 number of events STANDARD_DEVIATION 1.9 | 0.8 number of events STANDARD_DEVIATION 1.7 | 0.9 number of events STANDARD_DEVIATION 1.8 |
| Number of Symptomatic Hypoglycemic Events | 1.9 number of events STANDARD_DEVIATION 2.4 | 2.0 number of events STANDARD_DEVIATION 2.6 | 1.9 number of events STANDARD_DEVIATION 2.5 |
| # of Adults Living with | 3.1 number of people STANDARD_DEVIATION 1.8 | 2.8 number of people STANDARD_DEVIATION 1.3 | 2.9 number of people STANDARD_DEVIATION 1.6 |
| Pediatric Quality of Life Inventory 3.2 Diabetes Module (PedsQL 3.2 DM) Diabetes Management Score | 80.0 score on a scale STANDARD_DEVIATION 14.3 | 81.5 score on a scale STANDARD_DEVIATION 13.8 | 80.7 score on a scale STANDARD_DEVIATION 14 |
| Pediatric Quality of Life Inventory 3.2 Diabetes Module (PedsQL 3.2 DM) Diabetes Symptoms Score | 68.1 score on a scale STANDARD_DEVIATION 14.7 | 69.3 score on a scale STANDARD_DEVIATION 14 | 68.7 score on a scale STANDARD_DEVIATION 14.4 |
| Percent Time Above Range | 50.2 percentage of time STANDARD_DEVIATION 26.7 | 54.3 percentage of time STANDARD_DEVIATION 26.6 | 52.3 percentage of time STANDARD_DEVIATION 26.7 |
| Percent Time in Hypoglycemia | 10.9 percentage of time STANDARD_DEVIATION 10.2 | 10.7 percentage of time STANDARD_DEVIATION 11.2 | 10.8 percentage of time STANDARD_DEVIATION 10.7 |
| Percent Time in Range | 38.9 percentage of time STANDARD_DEVIATION 20.9 | 35.0 percentage of time STANDARD_DEVIATION 19.3 | 36.9 percentage of time STANDARD_DEVIATION 20.1 |
| Percent Time in Serious Hypoglycemia | 3.7 percentage of time STANDARD_DEVIATION 5 | 3.7 percentage of time STANDARD_DEVIATION 5.6 | 3.7 percentage of time STANDARD_DEVIATION 5.3 |
| Race/Ethnicity, Customized Ethnicity/Tribe Bengali | 124 Participants | 126 Participants | 250 Participants |
| Race/Ethnicity, Customized Ethnicity/Tribe Haya | 2 Participants | 4 Participants | 6 Participants |
| Race/Ethnicity, Customized Ethnicity/Tribe Kurya | 4 Participants | 4 Participants | 8 Participants |
| Race/Ethnicity, Customized Ethnicity/Tribe Other | 28 Participants | 20 Participants | 48 Participants |
| Race/Ethnicity, Customized Ethnicity/Tribe Sukuma | 41 Participants | 47 Participants | 88 Participants |
| Region of Enrollment Bangladesh | 124 participants | 126 participants | 250 participants |
| Region of Enrollment Tanzania | 75 participants | 75 participants | 150 participants |
| Retinopathy | 8 Participants | 6 Participants | 14 Participants |
| Sex: Female, Male Female | 107 Participants | 115 Participants | 222 Participants |
| Sex: Female, Male Male | 92 Participants | 86 Participants | 178 Participants |
| Socioeconomic Status Lower middle | 33 Participants | 29 Participants | 62 Participants |
| Socioeconomic Status Middle | 60 Participants | 63 Participants | 123 Participants |
| Socioeconomic Status Poor | 97 Participants | 96 Participants | 193 Participants |
| Socioeconomic Status Rice farmer | 1 Participants | 0 Participants | 1 Participants |
| Socioeconomic Status Upper middle | 6 Participants | 12 Participants | 18 Participants |
| Socioeconomic Status Well off/Rich | 2 Participants | 1 Participants | 3 Participants |
| Total Number of Units of Insulin per Day/Weight | 1.0 insulin units/kg per day STANDARD_DEVIATION 0.4 | 1.1 insulin units/kg per day STANDARD_DEVIATION 0.4 | 1.0 insulin units/kg per day STANDARD_DEVIATION 0.4 |
| Type of Insulin Regimen NPH + Regular with meals | 196 Participants | 196 Participants | 392 Participants |
| Type of Insulin Regimen Premixed 70/30 alone | 3 Participants | 3 Participants | 6 Participants |
| Type of Insulin Regimen Premixed 70/30 + Regular with meals | 0 Participants | 2 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 199 | 1 / 201 |
| other Total, other adverse events | 33 / 199 | 33 / 201 |
| serious Total, serious adverse events | 5 / 199 | 13 / 201 |
Outcome results
Primary
Time-in-range (TIR)
% time spent between 70 and 180mg/dl inclusive averaged across all daily measures. For 6-month outcome, these data were averaged across two CGM sensors (placed at 6 and 6.5 months). For 12-month outcome, these data were from one CGM sensor placed at 11.5 months.
Time frame: 6 and 12 months after randomization
Population: Randomized participants still on study with available CGM data at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Glargine | Time-in-range (TIR) | 6-month | 40.5 percentage of time | Standard Deviation 18.4 |
| Glargine | Time-in-range (TIR) | 12-month | 38.5 percentage of time | Standard Deviation 20.1 |
| NPH or Premixed 70/30 (Human Insulin) | Time-in-range (TIR) | 6-month | 38.1 percentage of time | Standard Deviation 18.1 |
| NPH or Premixed 70/30 (Human Insulin) | Time-in-range (TIR) | 12-month | 37.7 percentage of time | Standard Deviation 19.7 |
Comparison: 6-month (primary)p-value: 0.71Regression, Linear
Comparison: 12-monthp-value: 0.64Regression, Linear
Primary
Time-in-serious Hypoglycemia
% time spent less than 54 mg/dl averaged across all daily measures. For 6-month outcome, these data were averaged across two CGM sensors (placed at 6 and 6.5 months). For 12-month outcome, these data were from one CGM sensor placed at 11.5 months.
Time frame: 6 and 12 months after randomization
Population: Randomized participants still on study with available CGM data at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Glargine | Time-in-serious Hypoglycemia | 6-month | 3.6 percentage of time | Standard Deviation 5.6 |
| Glargine | Time-in-serious Hypoglycemia | 12-month | 2.4 percentage of time | Standard Deviation 3.5 |
| NPH or Premixed 70/30 (Human Insulin) | Time-in-serious Hypoglycemia | 6-month | 3.4 percentage of time | Standard Deviation 4.3 |
| NPH or Premixed 70/30 (Human Insulin) | Time-in-serious Hypoglycemia | 12-month | 3.8 percentage of time | Standard Deviation 5.5 |
Comparison: 6-month (primary)p-value: 0.43Regression, Linear
Comparison: 12-monthp-value: 0.008Regression, Linear
Secondary
Glycemic Control (HbA1c)
Mean HbA1c lab result reported as percent, which is typically how it is reported.
Time frame: baseline, 3, 6, 9 and 12 months after randomization
Population: Randomized participants still on study with available HbA1c data at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Glargine | Glycemic Control (HbA1c) | 12-month | 9.4 percent | Standard Deviation 2.3 |
| Glargine | Glycemic Control (HbA1c) | 3-month | 9.3 percent | Standard Deviation 2.5 |
| Glargine | Glycemic Control (HbA1c) | Baseline | 9.7 percent | Standard Deviation 2.8 |
| Glargine | Glycemic Control (HbA1c) | 6-month | 9.4 percent | Standard Deviation 2.3 |
| Glargine | Glycemic Control (HbA1c) | 9-month | 9.5 percent | Standard Deviation 2.1 |
| NPH or Premixed 70/30 (Human Insulin) | Glycemic Control (HbA1c) | 6-month | 9.5 percent | Standard Deviation 2.4 |
| NPH or Premixed 70/30 (Human Insulin) | Glycemic Control (HbA1c) | 9-month | 9.4 percent | Standard Deviation 2.2 |
| NPH or Premixed 70/30 (Human Insulin) | Glycemic Control (HbA1c) | 12-month | 9.4 percent | Standard Deviation 2.5 |
| NPH or Premixed 70/30 (Human Insulin) | Glycemic Control (HbA1c) | Baseline | 9.9 percent | Standard Deviation 2.8 |
| NPH or Premixed 70/30 (Human Insulin) | Glycemic Control (HbA1c) | 3-month | 9.4 percent | Standard Deviation 2.5 |
Comparison: 6-monthp-value: 0.81Regression, Linear
Comparison: 12-monthp-value: 0.29Regression, Linear
Secondary
Insulin Treatment Satisfaction Questionnaire (ITSQ) Scores
The ITSQ is composed of 22 items. A total 22-item score is reported, and the items are also divided into five subscales: Regimen Inconvenience (5 items), Lifestyle Flexibility (3 items), Glycemic Control (3 items), Hypoglycemic Control (5 items), and Insulin Delivery Device Satisfaction (6 items). Items use 7-point Likert scale responses, ranging from 1 (positive, e.g. No bother at all) to 7 (negative, e.g. A tremendous bother), though the specific response labels vary by question. Items were reverse scored and transformed to range from 0 to 100. Higher scores indicate higher treatment satisfaction.
Time frame: Baseline and at 6 and 12 months after randomization
Population: Randomized participants still on study with available ITSQ data at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Glargine | Insulin Treatment Satisfaction Questionnaire (ITSQ) Scores | Baseline | 75.0 score on a scale | Standard Deviation 14.4 |
| Glargine | Insulin Treatment Satisfaction Questionnaire (ITSQ) Scores | 6-month | 84.1 score on a scale | Standard Deviation 9 |
| Glargine | Insulin Treatment Satisfaction Questionnaire (ITSQ) Scores | 12-month | 87.1 score on a scale | Standard Deviation 7.9 |
| NPH or Premixed 70/30 (Human Insulin) | Insulin Treatment Satisfaction Questionnaire (ITSQ) Scores | Baseline | 75.6 score on a scale | Standard Deviation 14.4 |
| NPH or Premixed 70/30 (Human Insulin) | Insulin Treatment Satisfaction Questionnaire (ITSQ) Scores | 6-month | 82.1 score on a scale | Standard Deviation 11.1 |
| NPH or Premixed 70/30 (Human Insulin) | Insulin Treatment Satisfaction Questionnaire (ITSQ) Scores | 12-month | 85.9 score on a scale | Standard Deviation 8.6 |
Comparison: 6-monthp-value: 0.04Regression, Linear
Comparison: 12-monthp-value: 0.1Regression, Linear
Secondary
Nocturnal Hypoglycemic Events
Number of events defined as ≥15 minutes in duration \<70 mg/dL between midnight and 6:00 am; specifically, at least 2 sensor values \<70 mg/dL that are ≥15 minutes apart plus no intervening values ≥70 mg/dL For 6-month outcome, these data were averaged across two CGM sensors (placed at 6 and 6.5 months). For 12-month outcome, these data were from one CGM sensor placed at 11.5 months.
Time frame: 6 and 12 months after randomization
Population: Randomized participants still on study with available CGM data during nocturnal hours at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Glargine | Nocturnal Hypoglycemic Events | 6-month | 3.5 number of events | Standard Deviation 2.6 |
| Glargine | Nocturnal Hypoglycemic Events | 12-month | 3.2 number of events | Standard Deviation 2.7 |
| NPH or Premixed 70/30 (Human Insulin) | Nocturnal Hypoglycemic Events | 6-month | 3.6 number of events | Standard Deviation 2.7 |
| NPH or Premixed 70/30 (Human Insulin) | Nocturnal Hypoglycemic Events | 12-month | 4.2 number of events | Standard Deviation 3.5 |
Comparison: 6-monthp-value: 0.7Regression, Linear
Comparison: 12-monthp-value: 0.02Regression, Linear
Secondary
Pediatric Quality of Life Inventory 3.2 Diabetes Module (PedsQL 3.2 DM) Diabetes Management Score
Mean PedsQL 3.2 DM Diabetes Management score. PedsQL 3.2 DM Diabetes Management scale is composed of 18 items. All items use the same 5-point Likert response scale, with responses ranging from never (0) to almost always (4). Items are reverse scored and transformed on a scale ranging from 0 to 100. Higher scores indicate fewer diabetes management problems and therefore improved D-HRQoL.
Time frame: Baseline and at 6 and 12 months after randomization
Population: Randomized participants still on study with available PedsQL data at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Glargine | Pediatric Quality of Life Inventory 3.2 Diabetes Module (PedsQL 3.2 DM) Diabetes Management Score | Baseline | 80.0 score on a scale | Standard Deviation 14.3 |
| Glargine | Pediatric Quality of Life Inventory 3.2 Diabetes Module (PedsQL 3.2 DM) Diabetes Management Score | 6-month | 85.8 score on a scale | Standard Deviation 11.7 |
| Glargine | Pediatric Quality of Life Inventory 3.2 Diabetes Module (PedsQL 3.2 DM) Diabetes Management Score | 12-month | 88.0 score on a scale | Standard Deviation 11 |
| NPH or Premixed 70/30 (Human Insulin) | Pediatric Quality of Life Inventory 3.2 Diabetes Module (PedsQL 3.2 DM) Diabetes Management Score | Baseline | 81.5 score on a scale | Standard Deviation 13.8 |
| NPH or Premixed 70/30 (Human Insulin) | Pediatric Quality of Life Inventory 3.2 Diabetes Module (PedsQL 3.2 DM) Diabetes Management Score | 6-month | 85.7 score on a scale | Standard Deviation 11 |
| NPH or Premixed 70/30 (Human Insulin) | Pediatric Quality of Life Inventory 3.2 Diabetes Module (PedsQL 3.2 DM) Diabetes Management Score | 12-month | 88.8 score on a scale | Standard Deviation 10.3 |
Comparison: 6-monthp-value: 0.81Regression, Linear
Comparison: 12-monthp-value: 0.44Regression, Linear
Secondary
Pediatric Quality of Life Inventory 3.2 Diabetes Module (PedsQL 3.2 DM) Diabetes Symptoms Score
Mean PedsQL 3.2 DM Diabetes Symptoms score. PedsQL 3.2 DM Diabetes Symptoms scale is composed of 15 items. All items use the same 5-point Likert response scale, with responses ranging from never (0) to almost always (4). Items are reverse scored and transformed on a scale ranging from 0 to 100. The score is the sum of all the items over the number of items answered. Higher scores indicate fewer diabetes symptoms and therefore improved diabetes-specific health-related quality of life (D-HRQoL).
Time frame: Baseline and at 6 and 12 months after randomization
Population: Randomized participants still on study with available PedsQL data at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Glargine | Pediatric Quality of Life Inventory 3.2 Diabetes Module (PedsQL 3.2 DM) Diabetes Symptoms Score | Baseline | 68.1 score on a scale | Standard Deviation 14.7 |
| Glargine | Pediatric Quality of Life Inventory 3.2 Diabetes Module (PedsQL 3.2 DM) Diabetes Symptoms Score | 6-month | 74.6 score on a scale | Standard Deviation 14.4 |
| Glargine | Pediatric Quality of Life Inventory 3.2 Diabetes Module (PedsQL 3.2 DM) Diabetes Symptoms Score | 12-month | 75.9 score on a scale | Standard Deviation 15.1 |
| NPH or Premixed 70/30 (Human Insulin) | Pediatric Quality of Life Inventory 3.2 Diabetes Module (PedsQL 3.2 DM) Diabetes Symptoms Score | Baseline | 69.3 score on a scale | Standard Deviation 14 |
| NPH or Premixed 70/30 (Human Insulin) | Pediatric Quality of Life Inventory 3.2 Diabetes Module (PedsQL 3.2 DM) Diabetes Symptoms Score | 6-month | 75.2 score on a scale | Standard Deviation 14.1 |
| NPH or Premixed 70/30 (Human Insulin) | Pediatric Quality of Life Inventory 3.2 Diabetes Module (PedsQL 3.2 DM) Diabetes Symptoms Score | 12-month | 76.9 score on a scale | Standard Deviation 14.5 |
Comparison: 6-monthp-value: 0.95Regression, Linear
Comparison: 12-monthp-value: 0.73Regression, Linear
Secondary
Rate of Diabetic Ketoacidosis (DKA)
Hospitalization or Emergency Room Visit (serious adverse event) with primary diagnosis of Diabetic Ketoacidosis. This was measured by self-report and confirmed through review of hospital records
Time frame: 6 and 12 months after randomization
Population: Randomized participants who knew whether or not they had an event at least one of the time points post-baseline/run-in phase.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Glargine | Rate of Diabetic Ketoacidosis (DKA) | 6-month | 0 events per 1000 person years |
| Glargine | Rate of Diabetic Ketoacidosis (DKA) | 12-month | 0 events per 1000 person years |
| NPH or Premixed 70/30 (Human Insulin) | Rate of Diabetic Ketoacidosis (DKA) | 6-month | 0 events per 1000 person years |
| NPH or Premixed 70/30 (Human Insulin) | Rate of Diabetic Ketoacidosis (DKA) | 12-month | 0 events per 1000 person years |
Comparison: Through 6-monthp-value: 0.83Negative Binomial Regression
Comparison: Through 12-monthp-value: 0.09Negative Binomial Regression
Secondary
Rate of Severe Hypoglycemic Events
Severe hypoglycemic events (requiring assistance of another person to correct) reported by participant per 1000 person-years
Time frame: 6 and 12 months after randomization
Population: Randomized participants who knew whether or not they had an event at least one of the time points post-baseline/run-in phase.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Glargine | Rate of Severe Hypoglycemic Events | 6-month | 0 events per 1000 person years |
| Glargine | Rate of Severe Hypoglycemic Events | 12-month | 1.33 events per 1000 person years |
| NPH or Premixed 70/30 (Human Insulin) | Rate of Severe Hypoglycemic Events | 6-month | 3.11 events per 1000 person years |
| NPH or Premixed 70/30 (Human Insulin) | Rate of Severe Hypoglycemic Events | 12-month | 1.41 events per 1000 person years |
Comparison: Through 6-monthp-value: 0.98Negative Binomial Regression
Comparison: Through 12-monthp-value: 0.61Negative Binomial Regression
Secondary
Time-above-range
% time spent greater than 180mg/dl averaged across all daily measures. For 6-month outcome, these data were averaged across two CGM sensors (placed at 6 and 6.5 months). For 12-month outcome, these data were from one CGM sensor placed at 11.5 months.
Time frame: 6 and 12 months after randomization
Population: Randomized participants still on study with available CGM data at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Glargine | Time-above-range | 6-month | 48.7 percentage of time | Standard Deviation 22.7 |
| Glargine | Time-above-range | 12-month | 52.1 percentage of time | Standard Deviation 24.9 |
| NPH or Premixed 70/30 (Human Insulin) | Time-above-range | 6-month | 51.8 percentage of time | Standard Deviation 23.4 |
| NPH or Premixed 70/30 (Human Insulin) | Time-above-range | 12-month | 51.1 percentage of time | Standard Deviation 26 |
Comparison: 6-monthp-value: 0.58Regression, Linear
Comparison: 12-monthp-value: 0.21Regression, Linear
Secondary
Time-in-hypoglycemia
% time spent less than 70mg/dl averaged across all daily measures. For 6-month outcome, these data were averaged across two CGM sensors (placed at 6 and 6.5 months). For 12-month outcome, these data were from one CGM sensor placed at 11.5 months.
Time frame: 6 and 12 months after randomization
Population: Randomized participants still on study with available CGM data at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Glargine | Time-in-hypoglycemia | 12-month | 9.4 percentage of time | Standard Deviation 10.4 |
| Glargine | Time-in-hypoglycemia | 6-month | 10.8 percentage of time | Standard Deviation 9.5 |
| NPH or Premixed 70/30 (Human Insulin) | Time-in-hypoglycemia | 6-month | 10.2 percentage of time | Standard Deviation 8.5 |
| NPH or Premixed 70/30 (Human Insulin) | Time-in-hypoglycemia | 12-month | 11.2 percentage of time | Standard Deviation 10.8 |
Comparison: 6-monthp-value: 0.54Regression, Linear
Comparison: 12-monthp-value: 0.07Regression, Linear