Type 1 Diabetes Mellitus
Conditions
Brief summary
This is a two-period study of participants with type 1 diabetes mellitus (T1DM). In each period, participants will receive once daily injections of stable dose LY2605541 or insulin glargine for 28 to 35 days followed by procedures to look at how the body uses or stores fats and sugars. Participants will continue to use meal time insulin throughout the study. Healthy participants will also enroll in the study. They will not receive any study medication.
Interventions
BIOLOGICALLY2605541
Administered SQ
BIOLOGICALInsulin Glargine
Administered SQ
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
Type 1 Diabetics: \- T1DM for more than 1 year with Hemoglobin A1c (HbA1c) of less than 9.5% All Participants: * Otherwise fit and healthy * Non smoker
Exclusion criteria
Type 1 Diabetics: * Taking medication or supplements other than insulin to control diabetes * Suffered a hypoglycemic event in the last 12 months that required hospitalization or have poor awareness of hypoglycemia All Participants: \- Taking fibrates, thyroid replacement therapy, testosterone, beta blockers or systemic corticosteroids
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sleep Respiratory Quotient (RQ) in Type 1 Diabetes Mellitus (T1DM) | Day 30 post dose, overnight period (0000 to 0600 hours) | Lipid or glucose metabolism was assessed by the measurement of respiratory quotient (RQ) during sleep using whole room calorimetry. RQ is a calculation of basal metabolic rate (BMR) when estimated from carbon dioxide production. It is calculated from the ratio of carbon dioxide produced by the body to oxygen consumed by the body using whole room calorimetry (WRC). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Lipid Oxidation in T1DM and Healthy Participants | Day 30 post dose, overnight period (0000 to 0600 hours) | Lipid oxidation is derived from RQ, basal metabolic rate and urinary nitrogen, a value of 0.7 indicates that lipids are being metabolized. |
| Basal Metabolic Rate (BMR) for T1DM | Day 30 post dose, overnight period (0000 to 0600 hours) | BMR is the metabolic rate determined at rest 12 to 14 hours after the last meal. |
| Sleep Respiratory Quotient (RQ) of Untreated Healthy Participants | Day 5, overnight period (0000 to 0600 hours) | The respiratory quotient (or RQ or respiratory coefficient), is a number used in calculations of basal metabolic rate (BMR) when estimated from carbon dioxide production. It is calculated from the ratio of carbon dioxide produced by the body to oxygen consumed by the body using whole room calorimetry. The overnight period was averaged based on all 1-minutes interval measurements for the duration of the overnight period. |
| Total Number of Minutes of Lipid Oxidation (RQ Below 7.6) in T1DM and Healthy Participants | Day 5, every minute through 23 hour period | The respiratory quotient (or RQ or respiratory coefficient), is a number used in calculations of basal metabolic rate (BMR) when estimated from carbon dioxide production. It is calculated from the ratio of carbon dioxide produced by the body to oxygen consumed by the body using whole room calorimetry.It is calculated from the ratio of carbon dioxide produced by the body to oxygen consumed by the body using whole data based on all 1-minutes interval measurements for the duration of the overnight period. |
| Change in RQ, Pre-breakfast to Post-breakfast Meal, in T1DM | Day 30 0830 to 0854 hours, Day 30 1000 to 1054 hours | The respiratory quotient (or RQ or respiratory coefficient), is a number used in calculations of basal metabolic rate (BMR) when estimated from carbon dioxide production. It is calculated from the ratio of carbon dioxide produced by the body to oxygen consumed by the body using whole room calorimetry. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All T1DM Participants with T1DM who received Insulin peglispro (LY260551) and insulin glargine SQ in either sequence group. | 15 |
| Control Untreated healthy participants who received no study drug. | 12 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Period 1 | Sponsor Decision | 1 | 1 | 0 |
| Period 1 | Withdrawal by Subject | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | All T1DM | Total | Control |
|---|---|---|---|
| Age, Continuous | 36.5 years STANDARD_DEVIATION 12.2 | 36.7 years STANDARD_DEVIATION 12 | 36.9 years STANDARD_DEVIATION 12.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 7 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 20 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| 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 | 1 Participants | 5 Participants | 4 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 | 14 Participants | 22 Participants | 8 Participants |
| Region of Enrollment United States | 15 Participants | 27 Participants | 12 Participants |
| Sex: Female, Male Female | 7 Participants | 13 Participants | 6 Participants |
| Sex: Female, Male Male | 8 Participants | 14 Participants | 6 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 | 5 / 13 | 3 / 15 | 1 / 12 |
| serious Total, serious adverse events | 0 / 13 | 0 / 15 | 0 / 12 |
Outcome results
Primary
Sleep Respiratory Quotient (RQ) in Type 1 Diabetes Mellitus (T1DM)
Lipid or glucose metabolism was assessed by the measurement of respiratory quotient (RQ) during sleep using whole room calorimetry. RQ is a calculation of basal metabolic rate (BMR) when estimated from carbon dioxide production. It is calculated from the ratio of carbon dioxide produced by the body to oxygen consumed by the body using whole room calorimetry (WRC).
Time frame: Day 30 post dose, overnight period (0000 to 0600 hours)
Population: All randomized participants with T1DM that received at least 1 dose of study drug. Data from 2 participants could not be used: one due to uncontrolled blood glucose and one due to an increase in thyroid medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Peglispro | Sleep Respiratory Quotient (RQ) in Type 1 Diabetes Mellitus (T1DM) | 0.822 ratio | Standard Deviation 0.026 |
| Insulin Glargine | Sleep Respiratory Quotient (RQ) in Type 1 Diabetes Mellitus (T1DM) | 0.846 ratio | Standard Deviation 0.033 |
Secondary
Basal Metabolic Rate (BMR) for T1DM
BMR is the metabolic rate determined at rest 12 to 14 hours after the last meal.
Time frame: Day 30 post dose, overnight period (0000 to 0600 hours)
Population: All randomized participants with T1DM that received at least 1 dose of study drug. Data from 2 participants could not be used: one due to uncontrolled blood glucose and one due to an increase in thyroid medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Peglispro | Basal Metabolic Rate (BMR) for T1DM | 1511.0 kcal/day | Standard Deviation 228.3 |
| Insulin Glargine | Basal Metabolic Rate (BMR) for T1DM | 1403.6 kcal/day | Standard Deviation 207.7 |
Secondary
Change in RQ, Pre-breakfast to Post-breakfast Meal, in T1DM
The respiratory quotient (or RQ or respiratory coefficient), is a number used in calculations of basal metabolic rate (BMR) when estimated from carbon dioxide production. It is calculated from the ratio of carbon dioxide produced by the body to oxygen consumed by the body using whole room calorimetry.
Time frame: Day 30 0830 to 0854 hours, Day 30 1000 to 1054 hours
Population: All randomized participants with T1DM that received at least 1 dose of study drug. Data from 2 participants could not be used: one due to uncontrolled blood glucose and one due to an increase in thyroid medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Peglispro | Change in RQ, Pre-breakfast to Post-breakfast Meal, in T1DM | 0.836 ratio | Standard Deviation 0.055 |
| Insulin Glargine | Change in RQ, Pre-breakfast to Post-breakfast Meal, in T1DM | 0.874 ratio | Standard Deviation 0.033 |
Secondary
Lipid Oxidation in T1DM and Healthy Participants
Lipid oxidation is derived from RQ, basal metabolic rate and urinary nitrogen, a value of 0.7 indicates that lipids are being metabolized.
Time frame: Day 30 post dose, overnight period (0000 to 0600 hours)
Population: All randomized participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Peglispro | Lipid Oxidation in T1DM and Healthy Participants | 0.892 grams per day (g/day) | Standard Deviation 0.024 |
| Insulin Glargine | Lipid Oxidation in T1DM and Healthy Participants | 0.900 grams per day (g/day) | Standard Deviation 0.024 |
| Control | Lipid Oxidation in T1DM and Healthy Participants | 0.906 grams per day (g/day) | Standard Deviation 0.02 |
Secondary
Sleep Respiratory Quotient (RQ) of Untreated Healthy Participants
The respiratory quotient (or RQ or respiratory coefficient), is a number used in calculations of basal metabolic rate (BMR) when estimated from carbon dioxide production. It is calculated from the ratio of carbon dioxide produced by the body to oxygen consumed by the body using whole room calorimetry. The overnight period was averaged based on all 1-minutes interval measurements for the duration of the overnight period.
Time frame: Day 5, overnight period (0000 to 0600 hours)
Population: All randomized, health participant who received no study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Peglispro | Sleep Respiratory Quotient (RQ) of Untreated Healthy Participants | 0.848 ratio | Standard Deviation 0.02 |
Secondary
Total Number of Minutes of Lipid Oxidation (RQ Below 7.6) in T1DM and Healthy Participants
The respiratory quotient (or RQ or respiratory coefficient), is a number used in calculations of basal metabolic rate (BMR) when estimated from carbon dioxide production. It is calculated from the ratio of carbon dioxide produced by the body to oxygen consumed by the body using whole room calorimetry.It is calculated from the ratio of carbon dioxide produced by the body to oxygen consumed by the body using whole data based on all 1-minutes interval measurements for the duration of the overnight period.
Time frame: Day 5, every minute through 23 hour period
Population: All randomized participants: T1DM participants that received at least 1 dose of study drug, Data from 2 participants could not be used:one due to uncontrolled blood glucose and one due to an increase in thyroid medication,data from 2 participants could not be used: 1 due to uncontrolled blood glucose and 1 due to an increase in thyroid medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Insulin Peglispro | Total Number of Minutes of Lipid Oxidation (RQ Below 7.6) in T1DM and Healthy Participants | 22 minutes |
| Insulin Glargine | Total Number of Minutes of Lipid Oxidation (RQ Below 7.6) in T1DM and Healthy Participants | 8 minutes |
| Control | Total Number of Minutes of Lipid Oxidation (RQ Below 7.6) in T1DM and Healthy Participants | 4.5 minutes |