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

The Effect of Treatment With Basal Insulin Peglispro or Insulin Glargine on Insulin Sensitivity and the Effect of Prandial Insulin Lispro in Patients With Type 2 Diabetes Mellitus

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Insulin Peglispro; Drug: Insulin Lispro; Drug: Insulin Glargine

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Chula Vista, California, United States, 91911
      • Profil Institute for Clinical Research Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Insulin Peglispro (with Insulin Lispro); Insulin peglispro, a once daily subcutaneous(SC) injection at bedtime for 5 weeks	Drug: Insulin Peglispro; Administered subcutaneously (SC), (U-100 formulation); Other Names: LY2605541; Drug: Insulin Lispro; Administered subcutaneously (SC), (U-100 formulation)
Active Comparator: Insulin Glargine (with Insulin Lispro); Insulin glargine, a once daily subcutaneous(SC) injection at bedtime for 5 weeks	Drug: Insulin Lispro; Administered subcutaneously (SC), (U-100 formulation); Drug: Insulin Glargine; Administered subcutaneously (SC), (U-100 formulation)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Day 33, last 30 minutes (final step) of euglycemic 2-step hyperinsulinemic clamp

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	Day 29:Upon waking, pre-breakfast, 1 hour (hr), 2 hr, 3 hr, 4 hr and 5 hr post breakfast
Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) for Insulin Lispro During Clamp		Day 33 during euglycemic 2-step hyperinsulinemic clamp

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start: July 1, 2014
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: July 21, 2014
• First Submitted That Met QC Criteria: July 21, 2014
• First Posted (Estimate): July 22, 2014

Study Record Updates

• Last Update Posted (Actual): November 1, 2018
• Last Update Submitted That Met QC Criteria: October 29, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism; Diabetes Mellitus; Diabetes Mellitus, Type 2; Insulin Resistance; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin Glargine; Insulin Lispro
• Other Study ID Numbers: 15407; I2R-MC-BIDV (Other Identifier: Eli Lilly and Company)