A Study To Compare the Effects of Insulin Peglispro and Glargine on Insulin Sensitivity and Meal Time Insulin Requirements in Type 2 Diabetics

Phase 1

Completed

Conditions: Diabetes Mellitus, Type 2

Interventions: Drug: Insulin Peglispro
Drug: Insulin Glargine
Drug: Insulin Lispro

Registration Number: NCT02197520

Lead Sponsor: Eli Lilly and Company

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 24

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Insulin Peglispro (with Insulin Lispro)	Insulin Lispro	Insulin peglispro, a once daily subcutaneous(SC) injection at bedtime for 5 weeks
Insulin Peglispro (with Insulin Lispro)	Insulin Peglispro	Insulin peglispro, a once daily subcutaneous(SC) injection at bedtime for 5 weeks
Insulin Glargine (with Insulin Lispro)	Insulin Glargine	Insulin glargine, a once daily subcutaneous(SC) injection at bedtime for 5 weeks
Insulin Glargine (with Insulin Lispro)	Insulin Lispro	Insulin glargine, a once daily subcutaneous(SC) injection at bedtime for 5 weeks

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) for Insulin Lispro During Clamp	Day 33 during euglycemic 2-step hyperinsulinemic clamp