Diabetes Mellitus, Type 2
Conditions
Brief summary
This study will look into insulin sensitivity (how the body responds to insulin) and effects of meals on type 2 diabetics comparing insulin peglispro to insulin glargine. The study has two treatment periods, each of which will last about four weeks. One drug (insulin peglispro or insulin glargine) will be administered in each period. Participants will receive both drugs during the study. Participants may remain on stable dose metformin, as prescribed by their personal physician.
Interventions
Administered subcutaneously (SC), (U-100 formulation)
DRUGInsulin Glargine
Administered subcutaneously (SC), (U-100 formulation)
DRUGInsulin Lispro
Administered subcutaneously (SC), (U-100 formulation)
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 65 Years
Healthy volunteers
No
Inclusion criteria
* Stable glycated hemoglobin (HbA1c) less than (\<) 10.0 percent (%) * Stable dose of either 0.2 to 1.5 units per kilogram per day (U/kg/day) basal insulin or a total daily insulin dose l\<2.0 units per kilogram (U/kg) * C-peptide \<0.3 nanomole per liter (nmol/L) * Stable body during the last 2 months
Exclusion criteria
* Corrected QT interval (QTc) prolongation greater than (\>) 500 milliseconds (ms) or have any other abnormality in the 12 lead * Abnormal blood pressure * A history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine (apart from Type 1 Diabetes Mellitus (T1DM)), hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study medication; or of interfering with the interpretation of data * Currently treated with oral antidiabetic drugs (OADs) (excluding metformin and dipeptidyl peptidase-4 (DPP4) inhibitors), or glucagon-like peptide-1 (GLP-1) agonists or intend to use over-the counter or prescription medication, herbal medications, or nutritional supplements that affect PG or insulin sensitivity, impact on hypoglycemic awareness or promote weight loss within 4 weeks prior to randomization * Fasting triglycerides (TGs) \>400 milligrams per deciliter (mg/dL) (4.52 millimoles per liter (mmol/L)) * Have used systemic or inhaled corticosteroids/glucocorticoid therapy (excluding topical, intra-articular, and intraocular preparations) within 4 weeks prior to randomization * Currently receive insulin by pump or insulin degludec * Poorly controlled diabetes or known to have poor awareness of hypoglycemia * History of gastroparesis or gastrointestinal malabsorption * Require treatment with any drug other than insulin to treat diabetes * Previous history of proliferative retinopathy * Excessive consumers of xanthines
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacodynamics (PD): Average Glucose Infusion Rate From Euglycemic 2-step Hyperinsulinemic Clamp (M-value) | Day 33, last 30 minutes (final step) of euglycemic 2-step hyperinsulinemic clamp | During the euglycemic 2-step hyperinsulinemic clamp, both low and high insulin was infused sequentially during the same procedure. The 2-step clamp procedure allowed insulin sensitivity to be measured in participants and uses a lower dose of insulin of which the effect is largely on the liver and a high dose of insulin at which the effect has reached 100% on liver and effects are largely on glucose uptake in peripheral tissues. Measurements for average glucose infusion rate are collected for both steps (low and high) of the clamp procedure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) for Insulin Lispro During Clamp | Day 33 during euglycemic 2-step hyperinsulinemic clamp | — |
| Pharmacodynamics (PD): Plasma Glucose Area Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h), Above Pre Meal Baseline for Insulin Lispro | Days 30 through 32:Pre-dose, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes post-breakfast | — |
| Pharmacokinetics (PK): Area Under the Concentration Curve Concentration Curve Zero Through 5 Hours (AUC 0-5h) for Prandial Insulin Lispro | Days 30 through 32:Pre-dose, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes post-breakfast | — |
| Pharmacokinetics (PK): Area Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h) for Acetaminophen | Day 29:Pre-dose, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes post-breakfast | — |
| Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Day 29:Upon waking, pre-breakfast, 1 hour (hr), 2 hr, 3 hr, 4 hr and 5 hr post breakfast | VAS was scored from 0 - 100 millimeters (mm) as a perception of appetite and satiety (Flint et al. 2000), 0 being not hungry at all or nothing at all and 100 being extremely hungry and extremely large amount. The questions are abbreviated in table from: How hungry do you feel right now? to Hunger and How much food do you think you could eat right now? to Food amount. Scores were averaged and will be presented and calculated by a sum of the scores dividing by the total by the number of scores reported for timepoints. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants All participants who received Insulin peglispro, administered SC for 33 days then Insulin glargine, administered SC for 33 days or Insulin glargine, administered SC for 33 days then Insulin peglispro, administered SC for 33 days | 24 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 | Withdrawal by Subject | 1 | 0 |
| Period 2 | Adverse Event | 0 | 2 |
| Period 2 | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 51.3 years STANDARD_DEVIATION 9.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 24 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 20 Participants |
| Region of Enrollment United States | 24 Participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 14 / 24 | 10 / 23 |
| serious Total, serious adverse events | 0 / 24 | 0 / 23 |
Outcome results
Primary
Pharmacodynamics (PD): Average Glucose Infusion Rate From Euglycemic 2-step Hyperinsulinemic Clamp (M-value)
During the euglycemic 2-step hyperinsulinemic clamp, both low and high insulin was infused sequentially during the same procedure. The 2-step clamp procedure allowed insulin sensitivity to be measured in participants and uses a lower dose of insulin of which the effect is largely on the liver and a high dose of insulin at which the effect has reached 100% on liver and effects are largely on glucose uptake in peripheral tissues. Measurements for average glucose infusion rate are collected for both steps (low and high) of the clamp procedure.
Time frame: Day 33, last 30 minutes (final step) of euglycemic 2-step hyperinsulinemic clamp
Population: All participants who received at least 1 dose of study drug and had evaluable PD parameters.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Peglispro | Pharmacodynamics (PD): Average Glucose Infusion Rate From Euglycemic 2-step Hyperinsulinemic Clamp (M-value) | High Dose Insulin | 59.09 milligram*hour per deciliter | Standard Deviation 10.48 |
| Insulin Peglispro | Pharmacodynamics (PD): Average Glucose Infusion Rate From Euglycemic 2-step Hyperinsulinemic Clamp (M-value) | Low Dose Insulin | 17.22 milligram*hour per deciliter | Standard Deviation 6.24 |
| Insulin Glargine | Pharmacodynamics (PD): Average Glucose Infusion Rate From Euglycemic 2-step Hyperinsulinemic Clamp (M-value) | High Dose Insulin | 55.52 milligram*hour per deciliter | Standard Deviation 16.5 |
| Insulin Glargine | Pharmacodynamics (PD): Average Glucose Infusion Rate From Euglycemic 2-step Hyperinsulinemic Clamp (M-value) | Low Dose Insulin | 19.67 milligram*hour per deciliter | Standard Deviation 7.61 |
Secondary
Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29
VAS was scored from 0 - 100 millimeters (mm) as a perception of appetite and satiety (Flint et al. 2000), 0 being not hungry at all or nothing at all and 100 being extremely hungry and extremely large amount. The questions are abbreviated in table from: How hungry do you feel right now? to Hunger and How much food do you think you could eat right now? to Food amount. Scores were averaged and will be presented and calculated by a sum of the scores dividing by the total by the number of scores reported for timepoints.
Time frame: Day 29:Upon waking, pre-breakfast, 1 hour (hr), 2 hr, 3 hr, 4 hr and 5 hr post breakfast
Population: All participants who received at least 1 dose of study drug and had a VAS score.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Peglispro | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Food amount: 2 hour Post-breakfast | 20.7 millimeters | Standard Deviation 24.2 |
| Insulin Peglispro | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Hunger: Waking | 25.7 millimeters | Standard Deviation 23.2 |
| Insulin Peglispro | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Hunger:3 hour Post-breakfast | 34.8 millimeters | Standard Deviation 26.5 |
| Insulin Peglispro | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Hunger: 1 hour Post-breakfast | 7.8 millimeters | Standard Deviation 12.8 |
| Insulin Peglispro | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Food amount: 3 hour Post-breakfast | 35.6 millimeters | Standard Deviation 27.3 |
| Insulin Peglispro | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Hunger: Pre-breakfast | 41.5 millimeters | Standard Deviation 30.1 |
| Insulin Peglispro | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Hunger: 4 hour Post-breakfast | 46.6 millimeters | Standard Deviation 27.8 |
| Insulin Peglispro | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Food amount: 1 hour Post-breakfast | 8.7 millimeters | Standard Deviation 12.2 |
| Insulin Peglispro | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Food amount: 4 hour Post-breakfast | 48.2 millimeters | Standard Deviation 27.5 |
| Insulin Peglispro | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Food amount: Waking | 30.2 millimeters | Standard Deviation 23.9 |
| Insulin Peglispro | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Hunger: 5 hour Post-breakfast | 56.8 millimeters | Standard Deviation 28.6 |
| Insulin Peglispro | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Hunger: 2 hour Post-breakfast | 19.7 millimeters | Standard Deviation 23.5 |
| Insulin Peglispro | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Food amount: 5 hour Post-breakfast | 57.5 millimeters | Standard Deviation 27.2 |
| Insulin Peglispro | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Food amount: Pre-breakfast | 43.9 millimeters | Standard Deviation 27.7 |
| Insulin Glargine | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Food amount: 5 hour Post-breakfast | 53.4 millimeters | Standard Deviation 34.4 |
| Insulin Glargine | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Food amount: Waking | 34.4 millimeters | Standard Deviation 25.6 |
| Insulin Glargine | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Hunger: Pre-breakfast | 51.4 millimeters | Standard Deviation 32.8 |
| Insulin Glargine | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Food amount: Pre-breakfast | 51.5 millimeters | Standard Deviation 30.2 |
| Insulin Glargine | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Hunger: 1 hour Post-breakfast | 6.2 millimeters | Standard Deviation 16.4 |
| Insulin Glargine | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Food amount: 1 hour Post-breakfast | 6.0 millimeters | Standard Deviation 11.6 |
| Insulin Glargine | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Hunger: 2 hour Post-breakfast | 14.9 millimeters | Standard Deviation 19.4 |
| Insulin Glargine | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Food amount: 2 hour Post-breakfast | 16.3 millimeters | Standard Deviation 17.4 |
| Insulin Glargine | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Hunger:3 hour Post-breakfast | 29.2 millimeters | Standard Deviation 20.8 |
| Insulin Glargine | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Food amount: 3 hour Post-breakfast | 31.1 millimeters | Standard Deviation 20.6 |
| Insulin Glargine | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Hunger: 4 hour Post-breakfast | 48.0 millimeters | Standard Deviation 28.3 |
| Insulin Glargine | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Food amount: 4 hour Post-breakfast | 48.5 millimeters | Standard Deviation 28.2 |
| Insulin Glargine | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Hunger: 5 hour Post-breakfast | 55.5 millimeters | Standard Deviation 34.1 |
| Insulin Glargine | Appetite and Satiety Ratings, as Measured Using Visual Analog Scale (VAS) on Day 29 | Hunger: Waking | 38.6 millimeters | Standard Deviation 31.3 |
Secondary
Pharmacodynamics (PD): Plasma Glucose Area Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h), Above Pre Meal Baseline for Insulin Lispro
Time frame: Days 30 through 32:Pre-dose, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes post-breakfast
Population: All participants who received at least 1 dose of study drug and had evaluable PD parameters.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Insulin Peglispro | Pharmacodynamics (PD): Plasma Glucose Area Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h), Above Pre Meal Baseline for Insulin Lispro | 20% Insulin Lispro Dose | 334.23 milligram*hour per deciliter | Standard Deviation 165.96 |
| Insulin Peglispro | Pharmacodynamics (PD): Plasma Glucose Area Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h), Above Pre Meal Baseline for Insulin Lispro | 30% Insulin Lispro Dose | 244.68 milligram*hour per deciliter | Standard Deviation 136.01 |
| Insulin Peglispro | Pharmacodynamics (PD): Plasma Glucose Area Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h), Above Pre Meal Baseline for Insulin Lispro | 10% Insulin Lispro Dose | 437.78 milligram*hour per deciliter | Standard Deviation 147.47 |
| Insulin Glargine | Pharmacodynamics (PD): Plasma Glucose Area Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h), Above Pre Meal Baseline for Insulin Lispro | 20% Insulin Lispro Dose | 343.54 milligram*hour per deciliter | Standard Deviation 182.13 |
| Insulin Glargine | Pharmacodynamics (PD): Plasma Glucose Area Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h), Above Pre Meal Baseline for Insulin Lispro | 30% Insulin Lispro Dose | 239.83 milligram*hour per deciliter | Standard Deviation 175.54 |
| Insulin Glargine | Pharmacodynamics (PD): Plasma Glucose Area Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h), Above Pre Meal Baseline for Insulin Lispro | 10% Insulin Lispro Dose | 398.26 milligram*hour per deciliter | Standard Deviation 159.89 |
Secondary
Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) for Insulin Lispro During Clamp
Time frame: Day 33 during euglycemic 2-step hyperinsulinemic clamp
Population: No participant analyzed because Outcome Measure was incorrectly registered.
Secondary
Pharmacokinetics (PK): Area Under the Concentration Curve Concentration Curve Zero Through 5 Hours (AUC 0-5h) for Prandial Insulin Lispro
Time frame: Days 30 through 32:Pre-dose, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes post-breakfast
Population: All participants who received at least 1 dose of study drug and had evaluable PK parameters.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Insulin Peglispro | Pharmacokinetics (PK): Area Under the Concentration Curve Concentration Curve Zero Through 5 Hours (AUC 0-5h) for Prandial Insulin Lispro | 839 picomol*hour per liter | Standard Deviation 47 |
| Insulin Glargine | Pharmacokinetics (PK): Area Under the Concentration Curve Concentration Curve Zero Through 5 Hours (AUC 0-5h) for Prandial Insulin Lispro | 835 picomol*hour per liter | Standard Deviation 64 |
Secondary
Pharmacokinetics (PK): Area Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h) for Acetaminophen
Time frame: Day 29:Pre-dose, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 210, 240, 270, 300 minutes post-breakfast
Population: All participants who received at least 1 dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Peglispro | Pharmacokinetics (PK): Area Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h) for Acetaminophen | 33700 nanograms*hour per milliliter | Geometric Coefficient of Variation 28 |
| Insulin Glargine | Pharmacokinetics (PK): Area Under the Concentration Curve Zero Through 5 Hours (AUC 0-5h) for Acetaminophen | 35700 nanograms*hour per milliliter | Geometric Coefficient of Variation 31 |