Type 2 Diabetes Mellitus
Conditions
Keywords
diabetes, type 2 diabetes, insulin pump, continuous subcutaneous insulin infusion, CSII, A1C
Brief summary
This study will provide information on the use of insulin lispro and insulin aspart in insulin pumps in participants with type 2 diabetes.
Detailed description
This study will provide clinical information on the use of insulin lispro in continuous subcutaneous insulin infusion (CSII) in participants with type 2 diabetes. This study is designed to allow comparison of the 2 rapid-acting insulin analogs, with regard to their efficacy and safety, when used as a pump insulin therapy in this participant population. Each participant will be randomized to 1 of the 2 sequence groups in a 1:1 ratio and randomization will be stratified according to screening A1C (less than or equal to 8.0% or greater than 8.0%) and thiazolidinedione (TZD) use (yes or no). The study design includes the following periods: Screening/Randomization, Treatment Period 1 (16 weeks), and Treatment Period 2 (16 weeks).
Interventions
DRUGInsulin Lispro
Insulin lispro (100 U/mL) administered by CSII pump
DRUGInsulin Aspart
Insulin aspart (100 U/mL) administered by CSII pump
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Have type 2 diabetes (per World Health Organization \[WHO\] Classification of Diabetes) * Have been treated with CSII therapy using a rapid-acting analog for the previous 6 months * Have a screening A1C less than or equal to 9.0% (no lower limit for A1C) * Have a body mass index (BMI) less than 45 kilograms/square meter (kg/m²) at screening * Have a history of stable body weight (not varying by greater than 10% for at least 3 months prior to screening) * For participants on oral anti-diabetes medications (OAMs): must have been on a stable dose of OAMs, labeled for use with insulin, for at least 3 months prior to study entry
Exclusion criteria
* Have severe insulin resistance \[require greater than 2 units/kilogram/day (U/kg/day) of insulin\] * Are taking or have taken within the last 3 months, antihyperglycemic medication not approved for use with insulin, injectable non-insulin antihyperglycemic medications, or have a contraindication to current antihyperglycemic medication * Have a serum creatinine greater than or equal to 2 milligrams/deciliter (mg/dL) if not on metformin; known metabolic or lactic acidosis; any condition associated with hypoperfusion, hypoxemia, dehydration, or sepsis; and/or a radiologic contrast study within 48 hours prior to study entry * Are receiving chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy (excluding topical, intraocular, intraarticular, and inhaled preparations) or have received such therapy within 2 weeks immediately before screening * Have had more than 1 episode of hypoglycemia (defined as requiring assistance of a third party due to disabling hypoglycemia) within 6 months prior to entry into the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Glycosylated Hemoglobin A1C (HbA1c) at Endpoint | After 16 weeks of each treatment (Periods1 and 2) | Hemoglobin A1c (HbA1c) is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over the last 8-12 weeks. Least Squares (LS) means were adjusted for treatment, period, sequence, thiazolidinedione use (Yes/No), baseline HbA1c (\>8% or ≤8%) and participants. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Daily Insulin Dose | Week 16 of each treatment (Periods 1 and 2) | Total daily insulin dose was the average of the last 3 days total insulin dose immediately prior to the Week 16 (endpoint) visit of each treatment period. Least Squares (LS) means were adjusted for treatment, period, sequence, thiazolidinedione use (Yes/No), baseline Hemoglobin A1c (HbA1c) (\>8% or ≤8%) and participants. |
| Rate of Hypoglycemic Events Per 30 Days | Baseline through 16 weeks of each treatment (Periods 1 and 2) | A hypoglycemic episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia, or has blood glucose concentration of ≤70 milligrams/deciliter \[mg/dL (3.9 millimoles/liter (mmol/L)\]. Least Squares (LS) means were adjusted for treatment, period, sequence, baseline hypoglycemic event rate, thiazolidinedione use (Yes/No) and baseline Hemoglobin A1c (HbA1c) (\>8% or ≤8%). |
| Change From Baseline in Weight | Baseline, Week 16 of treatment Periods 1 and 2 | Least Squares (LS) means were adjusted for treatment, period, sequence, thiazolidinedione use (Yes/No), baseline Hemoglobin A1c (HbA1c) (\>8% or ≤8%), baseline weight and participants. |
| Percentage of Participants With Hypoglycemic Events | Baseline through 16 weeks of each treatment (Periods 1 and 2) | A hypoglycemic episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia, or has blood glucose concentration of ≤ 70 milligrams/deciliter \[mg/dL (3.9 millimoles/liter (mmol/L)\]. The percentage of participants is the total number of participants experiencing hypoglycemic events divided by number of participants in the treatment arm multiplied by 100. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Insulin Lispro / Insulin Aspart Insulin lispro \[100 units/milliliter (U/mL)\] administered by continuous subcutaneous insulin infusion (CSII) pump for 16 weeks in Treatment Period 1, followed by insulin aspart (100 U/mL) administered by CSII pump for 16 weeks in Treatment Period 2. | 60 |
| Insulin Aspart / Insulin Lispro Insulin aspart (100 U/mL) administered by CSII pump for 16 weeks in Treatment Period 1, followed by insulin lispro (100 U/mL) administered by CSII pump for 16 weeks in Treatment Period 2. | 62 |
| Total | 122 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Treatment Period 1 | Death | 1 | 0 |
| Treatment Period 1 | Physician Decision | 1 | 0 |
| Treatment Period 1 | Protocol Violation | 0 | 1 |
| Treatment Period 1 | Withdrawal by Subject | 1 | 3 |
| Treatment Period 2 | Adverse Event | 1 | 1 |
| Treatment Period 2 | Death | 1 | 0 |
| Treatment Period 2 | Physician Decision | 0 | 1 |
| Treatment Period 2 | Protocol Violation | 1 | 0 |
| Treatment Period 2 | Sponsor decision | 1 | 0 |
| Treatment Period 2 | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Insulin Lispro / Insulin Aspart | Insulin Aspart / Insulin Lispro | Total |
|---|---|---|---|
| Age, Continuous | 58.73 years STANDARD_DEVIATION 10.41 | 60.40 years STANDARD_DEVIATION 9.72 | 59.58 years STANDARD_DEVIATION 10.06 |
| Race/Ethnicity, Customized Hispanic or Latino | 2 participants | 1 participants | 3 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 58 participants | 61 participants | 119 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 5 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 2 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 | 53 Participants | 54 Participants | 107 Participants |
| Region of Enrollment United States | 60 participants | 62 participants | 122 participants |
| Sex: Female, Male Female | 33 Participants | 32 Participants | 65 Participants |
| Sex: Female, Male Male | 27 Participants | 30 Participants | 57 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 59 / 118 | 62 / 119 |
| serious Total, serious adverse events | 15 / 118 | 14 / 119 |
Outcome results
Primary
Glycosylated Hemoglobin A1C (HbA1c) at Endpoint
Hemoglobin A1c (HbA1c) is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over the last 8-12 weeks. Least Squares (LS) means were adjusted for treatment, period, sequence, thiazolidinedione use (Yes/No), baseline HbA1c (\>8% or ≤8%) and participants.
Time frame: After 16 weeks of each treatment (Periods1 and 2)
Population: All randomized participants who received at least 1 dose of study drug and had HbA1c measured at Week 16 of treatment Period 1 or 2. Participants were analyzed based on the treatment they received.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Lispro | Glycosylated Hemoglobin A1C (HbA1c) at Endpoint | 7.50 percentage of glycosylated hemoglobin | Standard Error 0.12 |
| Insulin Aspart | Glycosylated Hemoglobin A1C (HbA1c) at Endpoint | 7.40 percentage of glycosylated hemoglobin | Standard Error 0.12 |
95% CI: [-0.002, 0.21]Mixed Models Analysis
Secondary
Change From Baseline in Weight
Least Squares (LS) means were adjusted for treatment, period, sequence, thiazolidinedione use (Yes/No), baseline Hemoglobin A1c (HbA1c) (\>8% or ≤8%), baseline weight and participants.
Time frame: Baseline, Week 16 of treatment Periods 1 and 2
Population: All randomized participants who received at least 1 dose of study drug and had weight measured at baseline and Week 16 of Treatment Period 1 or 2. Participants were analyzed based on the treatment they received.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Lispro | Change From Baseline in Weight | 0.31 kilograms (kg) | Standard Error 0.53 |
| Insulin Aspart | Change From Baseline in Weight | 0.89 kilograms (kg) | Standard Error 0.52 |
p-value: 0.216Grizzle Model
Secondary
Percentage of Participants With Hypoglycemic Events
A hypoglycemic episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia, or has blood glucose concentration of ≤ 70 milligrams/deciliter \[mg/dL (3.9 millimoles/liter (mmol/L)\]. The percentage of participants is the total number of participants experiencing hypoglycemic events divided by number of participants in the treatment arm multiplied by 100.
Time frame: Baseline through 16 weeks of each treatment (Periods 1 and 2)
Population: All randomized participants who received at least 1 dose of study drug. Participants were analyzed based on the treatment they received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin Lispro | Percentage of Participants With Hypoglycemic Events | 71.2 percentage of participants |
| Insulin Aspart | Percentage of Participants With Hypoglycemic Events | 74.8 percentage of participants |
p-value: 0.471Prescott test
Secondary
Rate of Hypoglycemic Events Per 30 Days
A hypoglycemic episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia, or has blood glucose concentration of ≤70 milligrams/deciliter \[mg/dL (3.9 millimoles/liter (mmol/L)\]. Least Squares (LS) means were adjusted for treatment, period, sequence, baseline hypoglycemic event rate, thiazolidinedione use (Yes/No) and baseline Hemoglobin A1c (HbA1c) (\>8% or ≤8%).
Time frame: Baseline through 16 weeks of each treatment (Periods 1 and 2)
Population: All randomized participants who received at least 1 dose of study drug. Participants were analyzed based on the treatment they received.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Lispro | Rate of Hypoglycemic Events Per 30 Days | 2.24 hypoglycemic events per 30 days | Standard Error 0.28 |
| Insulin Aspart | Rate of Hypoglycemic Events Per 30 Days | 2.38 hypoglycemic events per 30 days | Standard Error 0.29 |
p-value: 0.522Negative binomial
Secondary
Total Daily Insulin Dose
Total daily insulin dose was the average of the last 3 days total insulin dose immediately prior to the Week 16 (endpoint) visit of each treatment period. Least Squares (LS) means were adjusted for treatment, period, sequence, thiazolidinedione use (Yes/No), baseline Hemoglobin A1c (HbA1c) (\>8% or ≤8%) and participants.
Time frame: Week 16 of each treatment (Periods 1 and 2)
Population: All randomized participants who received at least 1 dose of study drug and had total daily insulin dose recorded during Treatment Period (TP) 1 or 2. If endpoint data was missing for a specific TP, last observation carried forward (LOCF) method was implemented for that respective TP. Participants were analyzed based on the treatment they received.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Lispro | Total Daily Insulin Dose | 80.41 units of insulin | Standard Error 4.78 |
| Insulin Aspart | Total Daily Insulin Dose | 80.69 units of insulin | Standard Error 4.77 |
95% CI: [-2.92, 2.35]Mixed Models Analysis