A Study of LY2605541 Versus Insulin Glargine on Blood Sugar

• LY2605541 (Drug): LY2605541 is a solution. The concentration of LY2605541 is 100 units/milliliter (U/mL).
• Insulin glargine (Other): Insulin glargine is a 100 U/mL solution in 10 milliliter (mL) glass vial.

Primary outcomes

• Part B: Glucodynamics: Endogenous Glucose Output [Baseline, up to 10 hours (duration of the euglycemic glucose clamp)]: The percent suppression from baseline in endogenous glucose production (EGP) is presented. Percent EGP change from baseline was calculated by (1-\[last 2 hours of EGP/basal EGP\])*100. The duration of the clamp procedure was 10 hours for the LY2605541 74.1 mU/min dose in Part B. The duration of the clamp procedures performed at the 15.3 mU/min LY2605541 dose and both of the insulin glargine doses was 8 hours.
• Part B: Glycodynamics: Glucose Disposal [Baseline, up to 10 hours (duration of the euglycemic glucose clamp)]: The fold change from baseline in glucose disappearance rate (GDR) is presented. The fold GDR increase from baseline was calculated by last 2 hours of GDR/basal GDR. The duration of the clamp procedure was 10 hours for the LY2605541 74.1 mU/min dose in Part B. The duration of the clamp procedures performed at the 15.3 mU/min LY2605541 dose and both of the insulin glargine doses was 8 hours.
• Part B: Glycodynamics: Maximum Rate of Glucose Disposal [Baseline, up to 10 hours (duration of the euglycemic glucose clamp)]: The maximum rate of glucose disposal (Rdmax) is presented. The duration of the clamp procedure was 10 hours for the LY2605541 74.1 mU/min dose in Part B. The duration of the clamp procedures performed at the 15.3 mU/min LY2605541 dose and both of the insulin glargine doses was 8 hours.

Sex: Male, ages: 18 Years to 50 Years, accepts healthy volunteers

Inclusion Criteria:

All Participants

* Are healthy males or participants with T1DM
* Have a screening body mass index (BMI) of 20.0-29.9 kilograms per square meter (kg/m\^2)

Healthy Participants ONLY

* Are overtly healthy, as determined by medical history and physical examination
* Have a fasting blood glucose <108 milligrams/deciliter (mg/dL) (6.0 millimoles/liter \[mmol/L\]) at screening

Participants with T1DM ONLY

* Have a diagnosis of T1DM for at least 1 year based on medical history
* Have a screening c-peptide <0.5 nanograms/milliliter (ng/mL)
* Have a hemoglobin A1c (HbA1c) of 6.0 to 9.0% at screening
* Have had no episodes of severe hypoglycemia in the past 6 months

Exclusion Criteria:

All Participants

* Have a hemoglobin level <12.0 grams/deciliter (g/dL)
* Are currently a smoker, used tobacco products on a regular basis in the 6 months prior to screening, or are intending to smoke during the study

Healthy Participants ONLY

• Regular use or intended use of over-the counter or prescription medication within 7 and 14 days, respectively, prior to dosing (apart from vitamin/mineral supplements or occasional use of acetaminophen or ibuprofen).

Participants with T1DM ONLY

* Regular use or intended use of any over-the-counter or prescription medications or nutritional supplements that affect blood glucose or the body's sensitivity to insulin or that promote weight loss within 14 days prior to dosing
* Are receiving chronic (lasting longer than 14 consecutive days) systemic or inhaled glucocorticoid therapy (excluding topical, intra-articular, and intraocular preparations) or have received such therapy within the 4 weeks before dosing
* Require a total daily insulin dose exceeding 100 units (U)
* Have fasting triglycerides >400 mg/dL

Participant flow

Outcome results

• Part B: Glucodynamics: Endogenous Glucose Output (Primary), Mean, percent of suppression: 15.3 mU/Min LY2605541 64.53 +/- 19.35; 74.1 mU/Min LY2605541 99.23 +/- 1.76; 10 mU/m^2/Min Insulin Glargine 78.05 +/- 17.33; 20 mU/m^2/Min Insulin Glargine 97.05 +/- 6.47
• Part B: Glycodynamics: Glucose Disposal (Primary), Mean, fold change: 15.3 mU/Min LY2605541 0.68 +/- 0.09; 74.1 mU/Min LY2605541 1.42 +/- 0.35; 10 mU/m^2/Min Insulin Glargine 0.98 +/- 0.39; 20 mU/m^2/Min Insulin Glargine 1.85 +/- 0.59
• Part B: Glycodynamics: Maximum Rate of Glucose Disposal (Primary), Geometric mean, milligrams/minute/kilograms (mg/min/kg): 15.3 mU/Min LY2605541 1.80 +/- 24; 74.1 mU/Min LY2605541 2.89 +/- 23; 10 mU/m^2/Min Insulin Glargine 2.15 +/- 28; 20 mU/m^2/Min Insulin Glargine 3.55 +/- 40

Adverse events

Other adverse events by term

• Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Study director, Eli Lilly and Company