IMAGINE 1: A Study in Participants With Type 1 Diabetes Mellitus

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01481779
• Collaborator: (none)
• Enrollment: 455
• Locations: 51
• Arms: 2
• Duration (Months): 29
• Patients Per Site: 8.9
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is:

• To compare the blood sugar control of LY2605541 with insulin glargine after 78 weeks of treatment.

• To compare the rate of night-time low blood sugar episodes on LY2605541 with insulin glargine during 78 weeks of treatment.

• To compare the number of participants on LY2605541 reaching blood sugar targets without low blood sugar episodes at night to those taking insulin glargine after 78 weeks of treatment.

• To compare the rate of hypoglycemia episodes on LY2605541 with insulin glargine during 78 weeks of treatment.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 1	Drug: Glargine; Drug: LY2605541; Drug: Insulin Lispro	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 455 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The Impact of LY2605541 Versus Insulin Glargine for Patients With Type 1 Diabetes Mellitus Treated With Preprandial Insulin Lispro: An Open-Label, Randomized, 78-Week Study - The IMAGINE 1 Study
• Study Start Date: Jan 1, 2012
• Actual Primary Completion Date: May 1, 2013
• Actual Study Completion Date: Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LY2605541 + Insulin Lispro LY2605541 titrated based on blood glucose readings, administered by subcutaneous (SC) injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.	Drug: LY2605541; Administered by SC injection with a pen device.; Drug: Insulin Lispro; Administered by SC injection with a pen device.; Other Names: LY275585 Humalog
Active Comparator: Glargine + Insulin Lispro Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.	Drug: Glargine; Administered by SC injection via a pen device.; Drug: Insulin Lispro; Administered by SC injection with a pen device.; Other Names: LY275585 Humalog

Outcome Measures

Primary Outcome Measures

1. Hemoglobin A1c (HbA1c) at 26 Weeks [26 weeks]

   HbA1c is a test that measures a participant's average blood glucose level over a 2- to 3-month timeframe. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM), adjusting for treatment, stratification factors (baseline low-density lipoprotein cholesterol [LDL-C] [<100 milligrams per deciliter (mg/dL) and ≥100 mg/dL] and country), visit, treatment-by-visit interaction, and baseline HbA1c as the fixed effects and participant as the random effect.

Secondary Outcome Measures

1. Hemoglobin A1c (HbA1c) [52 weeks and 78 weeks]

   HbA1c is a test that measures a participant's average blood glucose level over a 2- to 3-month timeframe. LS means were calculated using MMRM, adjusting for treatment, stratification factors (baseline LDL-C [<100 mg/dL and ≥100 mg/dL] and country), visit, treatment-by-visit interaction, and baseline HbA1c as the fixed effects.

2. Change From Baseline in Hemoglobin A1c (HbA1c) [Baseline, 26 weeks, 52 weeks, 78 weeks]

   HbA1c is a test that measures a participant's average blood glucose level over a 2- to 3-month timeframe. LS means were calculated using MMRM, adjusting for treatment, stratification factors (baseline LDL-C [<100 mg/dL and ≥100 mg/dL] and country), visit, treatment-by-visit interaction, and baseline HbA1c as the fixed effects.

3. Percentage of Participants With Hemoglobin A1c (HbA1c) Less Than 7.0% or Less Than or Equal to 6.5% Using Last Observation Carried Forward (LOCF) [26 weeks and 52 weeks and 78 weeks]

   HbA1c is a test that measures a participant's average blood glucose level over a 2- to 3-month timeframe. The percentage of participants was calculated by dividing the number of participants reaching target HbA1c by the total number of participants analyzed, then multiplying by 100.

4. Proportion of Participants With Hemoglobin A1c (HbA1c) Less Than 7.0% Without Nocturnal Hypoglycemia [26 weeks and 52 weeks and 78 weeks]

   Hypoglycemic episodes are defined as an event that is associated with reported signs and symptoms of hypoglycemia and/or a documented blood glucose concentration of ≤70 mg/dL (3.9 millimoles per liter [mmol/L]). A nocturnal hypoglycemic event occurred between bedtime and waking and between the time points of 10:00 PM and 10:00 AM. The percentage of participants was calculated by dividing the number of participants with HbA1c <7.0% without nocturnal hypoglycemia by the total number of participants analyzed, then multiplying by 100.

5. Total Hypoglycemia Rates (Adjusted by 30 Days) [Baseline through 26 weeks and Baseline through 52 weeks and Baseline through 78 weeks]

   Hypoglycemic episodes are defined as events that are associated with reported signs and symptoms of hypoglycemia and/or documented blood glucose (BG) concentrations of ≤70 mg/dL (3.9 mmol/L). Group mean rates of total hypoglycemia (per 30 days) are presented and were calculated from negative binomial regression models (number of episodes = treatment + baseline total hypoglycemia rate, with log [exposure in days/30] as an offset variable). Group mean is estimated by taking the inverse link function on individual participant covariates first and then averages over all participants.

6. Percentage of Participants With Total Hypoglycemia Events [Baseline through 26 weeks and Baseline through 52 weeks and Baseline through 78 weeks]

   Hypoglycemic events are defined as events that are associated with reported signs and symptoms of hypoglycemia and/or documented BG concentrations of ≤70 mg/dL (3.9 mmol/L). The percentage of participants was calculated by dividing the number of participants with hypoglycemic episodes by the total number of participants analyzed, then multiplying by 100.

7. Nocturnal Hypoglycemia Rates (Adjusted by 30 Days) [Baseline through 26 weeks and Baseline through 52 weeks and Baseline through 78 weeks]

   Hypoglycemic episodes are defined as events that are associated with reported signs and symptoms of hypoglycemia and/or a documented BG concentration of ≤70 mg/dL (3.9 mmol/L). A nocturnal hypoglycemic event occurred between bedtime and waking and between the time points of 10:00 PM and 10:00 AM. Group mean rates of nocturnal hypoglycemia (per 30 days) are presented and were calculated from negative binomial regression models (number of episodes = treatment + baseline nocturnal hypoglycemia rate, with log [exposure in days/30] as an offset variable). Group mean is estimated by taking the inverse link function on individual participant covariates first and then averages over all participants.

8. Percentage of Participants With Nocturnal Hypoglycemic Events [Baseline through 26 weeks and Baseline through 52 weeks and Baseline through 78 weeks]

   Hypoglycemic episodes are defined as an event that is associated with reported signs and symptoms of hypoglycemia and/or a BG concentration of ≤70 mg/dL (3.9 mmol/L). A nocturnal hypoglycemic event occurred between bedtime and waking and between the time points of 10:00 PM and 10:00 AM. The percentage of participants was calculated by dividing the number of participants with nocturnal hypoglycemic episodes by the total number of participants analyzed, then multiplying by 100.

9. Fasting Serum Glucose (FSG) by Laboratory Measurement [26 weeks and 52 weeks and 78 weeks]

   LS means were calculated using MMRM, adjusting for treatment, stratification factors (baseline HbA1c [≤8.5% and >8.5%], baseline LDL-C level [<100 mg/dL and ≥100 mg/dL], and country), visit, treatment-by-visit interaction, and corresponding baseline dependent variable as the fixed effects, and participants as the random effect.

10. Fasting Blood Glucose (FBG) Intra-participant Variability [26 weeks and 52 weeks and 78 weeks]

    FBG was measured by self-monitored blood glucose (SMBG). Between-day glucose variability is measured by the standard deviation of FBG. LS means were calculated using MMRM, adjusting for treatment, stratification factors (baseline HbA1c [≤8.5% and >8.5%], baseline LDL-C level [<100 mg/dL and ≥100 mg/dL], and country), visit, treatment-by-visit interaction, and corresponding baseline dependent variable as the fixed effects, and participants as the random effect.

11. 0300-hour Blood Glucose (BG) to Fasting Blood (FBG) Glucose Excursion [26 weeks and 52 weeks and 78 weeks]

    Results of a 0300-hour to pre-morning meal (FBG) excursion are presented (only SMBG profiles with both 0300 hours and the next day pre-morning measurements are included for the calculation of such excursion). LS means were calculated using MMRM, adjusting for treatment, stratification factors (baseline HbA1c [≤8.5% and >8.5%], baseline LDL-C level [<100 mg/dL and ≥100 mg/dL], and country), visit, treatment-by-visit interaction, and corresponding baseline dependent variable as the fixed effects and participants as the random effect.

12. 9 Point Self-monitored Blood Glucose (SMBG) [26 weeks and 52 weeks and 78 weeks]

    9-point SMBG profiles were obtained over 2 days within the week prior to Weeks 0, 4, 12, 26, 39, 52, 65, and 78. SMBG measurements were taken at 9 time points: pre-morning meal, 2 hours post-morning meal, pre-midday meal, 2 hours post-midday meal, pre-evening meal, 2 hours post-evening meal, bedtime, at approximately 0300 hours, and the pre-morning meal the next day. LS means were calculated using MMRM, adjusting for treatment, stratification factors (baseline HbA1c [≤8.5% and >8.5%], baseline LDL-C level [<100 mg/dL and ≥100 mg/dL], and country), visit, treatment-by-visit interaction, and corresponding baseline dependent variable as the fixed effects and participants as the random effect.

13. Change From Baseline in Body Weight [Baseline and 26 weeks and 52 weeks and 78 weeks]

    LS means were calculated using MMRM, adjusting for treatment, stratification factors (baseline HbA1c [≤8.5% and >8.5%], baseline LDL-C level [<100 mg/dL and ≥100 mg/dL], and country), visit, treatment-by-visit interaction, and corresponding baseline dependent variable as the fixed effects, and participants as the random effect.

14. Basal, Bolus, and Total Insulin Dose [26 weeks and 52 weeks and 78 weeks]

    Basal insulin dose, short-acting bolus insulin dose (each meal and overall), and total insulin dose were calculated based on the dose during the last 7 days prior to the post-treatment visit or last 3 days prior to the randomization visit. LS means were calculated using MMRM, adjusting for treatment, stratification factors (baseline HbA1c [≤8.5% and >8.5%], baseline LDL-C level [<100 mg/dL and ≥100 mg/dL], and country), visit, treatment-by-visit interaction, and corresponding baseline dependent variable as the fixed effects and participants as the random effect.

15. Lipid Profile [26 weeks and 52 weeks and 78 weeks]

    Concentrations of cholesterol, high-density lipoprotein cholesterol (HDL-C), LDL-C, and triglycerides are summarized. LS means were calculated using MMRM, adjusting for stratification factors (baseline HbA1c [≤8.5% and >8.5%], country, LDL-C [<100 mg/dL and ≥100 mg/dL] except for the LDL-C outcome variable), visit, treatment, treatment-by-visit interaction, and baseline value of corresponding lipid outcome variable.

16. Percentage of Participants With Change in Anti-LY2605541 Antibodies [Baseline through 26 weeks and Baseline through 52 weeks and Baseline through 78 weeks]

    The percentage of participants with a treatment-emergent anti-LY2605541 antibody response (TEAR) is summarized. TEAR is defined as change from baseline to post-baseline in the anti-LY2605541 antibody level either from undetectable to detectable or from detectable to the value with at least 130% relative increase from baseline.

17. Insulin Treatment Satisfaction Questionnaire (ITSQ) [26 weeks]

    ITSQ is a validated instrument containing 22 items that assess treatment satisfaction for participants with diabetes and on insulin. The questionnaire measures satisfaction from the following 5 domains: Inconvenience of Regimen, Lifestyle Flexibility, Glycemic Control, Hypoglycemic Control, and Insulin Delivery Device. Data presented are the transformed overall score on a scale of 0-100, where higher scores indicate better treatment satisfaction. LS means were calculated using an analysis of covariance (ANCOVA) model with treatment and stratification (baseline HbA1c [≤8.5% or >8.5%] and country) as fixed effects and baseline value of the dependent variable as a covariate.

18. Low Blood Sugar Survey (LBSS) [26 weeks and 52 weeks and 78 weeks]

    LBSS (also referenced as Hypoglycemia Fear Survey - II [HFS-II]) is a 33-item questionnaire that measures 1) behaviors to avoid hypoglycemia and its negative consequences (15 items) and 2) worries about hypoglycemia and its negative consequences (18 items). Responses are made on a 5-point Likert scale where 0 = Never and 4 = Always. Total score is the sum of all items (range 0-132). Higher total scores reflect greater fear of hypoglycemia. LS means were calculated using MMRM, adjusting for treatment, stratification factors (baseline HbA1c [≤8.5% and >8.5%] and country), visit, treatment-by-visit interaction , and corresponding baseline dependent variable as the fixed effects and participants as the random effect.

19. European Quality of Life-5 Dimension (EQ-5D) [26 weeks]

    The EQ-5D is a generic, multidimensional, health-related, quality-of-life instrument. The profile allows participants to rate their health state in 5 health domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) using a 3-level scale of 1-3 (no problem, some problems, and extreme problems). These combinations of attributes are converted into a weighted health-state Index Score according to the United States population-based algorithm. Scores range from -0.11 to 1.0, where a score of 1.0 indicates perfect health. LS means were calculated using ANCOVA, adjusting for treatment and stratification factors (baseline HbA1c [≤8.5% or >8.5%] and country) as fixed effects and baseline EQ-5D score as a covariate.

20. Rapid Assessment of Physical Activity (RAPA) [26 weeks and 78 weeks]

    The RAPA questionnaire assesses the level and intensity of physical activity of adult participants. It contains 2 subscales: RAPA 1 (Aerobic) and RAPA 2 (Strength and Flexibility). RAPA 1 contains 7 questions regarding the participant's amount and intensity of physical activity, allowing each participant's aerobic activity level to be categorized as sedentary, underactive, light activities, light activity, regular underactive, or active. RAPA 2 contains 2 questions regarding participants' physical activities that increase strength and improve flexibility. Each participant's strength and flexibility activity level is then categorized as neither strength nor flexibility (flex) activity, either strength or flex (not both), both strength and flex activity. The percentage of participants in each RAPA 1/2 category is presented and was calculated by dividing the number of participants in each RAPA 1/2 category by the total number of participants analyzed, then multiplying by 100.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Have had diabetes mellitus for at least 1 year

• Have an hemoglobin A1c (HbA1c) value less than 12% according to the central laboratory at screening

• Have a body mass index (BMI) less than or equal to 35.0 kilograms per square meter (kg/m^2)

• Have been treated for at least 90 days prior to screening with the following:

• Insulin detemir, insulin glargine, or human insulin isophane suspension (NPH) insulin in combination with premeal insulin,

• Self-mixed or premixed insulin regimens with any basal and bolus insulin combination administered at least twice daily, or

• Continuous SC insulin infusion therapy

• This inclusion criterion applies to female participants:

• Are not breastfeeding

• Test negative for pregnancy at screening and randomization based on serum pregnancy tests

• Do not intend to become pregnant during the study

• Have practiced a reliable method of birth control (for example, use of oral contraceptives or levonorgestrel, diaphragms with contraceptive jelly, cervical caps with contraceptive jelly, condoms with contraceptive foam, intrauterine devices, partner with vasectomy, or abstinence) for at least 6 weeks prior to screening

• Agree to continue to use a reliable method of birth control during the study, as determined by the investigator (and for 2 weeks following the last dose of study drug)

• Capable of and willing and desirous to do the following: adhere to a multiple daily injection regimen, inject insulin with a prefilled pen and perform Self-Monitored Blood Glucose (SMBG) and record keeping as required by this protocol, as determined by the investigator. Caregiver may be responsible for all of the above.

Exclusion Criteria:

• Are using twice-daily insulin glargine having been inadequately controlled on once-daily dosed glargine prior to screening

• Have excessive insulin resistance defined as having received a total daily dose of insulin greater than 1.5 units per kilogram (units/kg) at the time of randomization

• Receiving any oral or injectable medication (other than metformin for treatment of polycystic ovarian disease) intended for the treatment of diabetes mellitus other than insulins in the 90 days prior to screening

• Lipid-lowering medications:

• Are using niacin preparations as a lipid-lowering medication and/or bile acid sequestrants within 90 days prior to screening or are using lipid-lowering medication at a dose that has not been stable for greater than or equal to 90 days prior to screening

• If a participant has not been on a stable dose of lipid-lowering medication for greater than or equal to 90 days prior to screening, the site should wait to screen the participant. If the results of the screening laboratory tests require a change to the participant's current lipid-lowering medication or initiation of lipid-lowering medication, it is acceptable to change the lipid-lowering medication for the participant and to have the participant return greater than or equal to 90 days later to complete some of the screening procedures again

• Have fasting hypertriglyceridemia (defined as greater than 4.5 millimoles per liter [mmol/L], greater than 400 milligrams per deciliter [mg/dL]) at screening, as determined by the central laboratory

• Have had more than 1 episode of severe hypoglycemia (defined as requiring assistance due to neurologically disabling hypoglycemia as determined by the investigator) within 6 months prior to entry into the study

• Have had 2 or more emergency room visits or hospitalizations due to poor glucose control (hyperglycemia or diabetic ketoacidosis) in the past 6 months

• Cardiovascular: have cardiac disease with functional status that is New York Heart Association Class III or IV (per New York Heart Association Cardiac Disease Classification)

• Renal: Have a history of renal transplantation or are currently receiving renal dialysis or have serum creatinine greater than 2.5 mg/dL

• Hepatic: Have obvious clinical signs or symptoms of liver disease (excluding non-alcoholic fatty liver disease [NAFLD]), acute or chronic hepatitis, non-alcoholic steatohepatitis (NASH), or elevated liver enzyme measurements as indicated below:

• Total bilirubin greater than or equal to 2 times the upper limit of normal (ULN) as defined by the central laboratory,

• Alanine aminotransferase (ALT)/(serum glutamic pyruvic transaminase (SGPT) greater than 2.5 times ULN as defined by the central laboratory, or

• Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) greater than 2.5 times ULN as defined by the central laboratory.

• Malignancy: Have active or untreated malignancy, have been in remission from clinically significant malignancy (other than basal cell or squamous cell skin cancer) for less than 5 years, or are at an increased risk for developing cancer or a recurrence of cancer in the opinion of the investigator

• Allergy: Have known hypersensitivity or allergy to any of the study insulins or their excipients

• Hematologic: Have had a blood transfusion or severe blood loss within 3 months prior to screening or have known hemoglobinopathy, hemolytic anemia, sickle cell anemia, or any other traits of hemoglobin abnormalities known to interfere with the HbA1c measurement

• Glucocorticoid therapy: Receiving chronic (lasting longer than 14 consecutive days) systemic glucocorticoid therapy (excluding topical , intraocular, intranasal, and inhaled preparations) or have received such therapy within 8 weeks immediately before screening with the exception of replacement therapy for adrenal insufficiency

• Diagnosed clinically significant diabetic autonomic neuropathy, in the opinion of the investigator

• Have any other condition (including known drug or alcohol abuse or psychiatric disorder including eating disorder) that precludes the participant from following and completing the protocol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Concord	California	United States	94520
2	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Escondido	California	United States	92026
3	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Fresno	California	United States	93720
4	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Greenbrae	California	United States	94904
5	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Huntington Beach	California	United States	92648
6	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	San Mateo	California	United States	94401
7	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Aurora	Colorado	United States	80010
8	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Idaho Falls	Idaho	United States	83404
9	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Las Vegas	Nevada	United States	89148
10	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Salt Lake City	Utah	United States	84102
11	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Renton	Washington	United States	98057
12	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Spokane	Washington	United States	99202
13	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Graz		Austria	8036
14	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Vienna		Austria	1130
15	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Bar Le Duc		France	55000
16	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Corbeil-Essonnes		France	91100
17	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Montpellier		France	34295
18	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Nantes		France	44093
19	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Nice		France	06002
20	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Saint Mande		France	94160
21	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Toulouse		France	31059
22	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Venissieux		France	69200
23	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Berlin		Germany	10409
24	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Eisenach		Germany	99817
25	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Falkensee		Germany	14612
26	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Hamburg		Germany	22559
27	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Mainz		Germany	55116
28	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Mayen		Germany	56727
29	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Münster		Germany	48153
30	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Neuwied		Germany	56564
31	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Pohlheim		Germany	35415
32	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Cagliari		Italy	09100
33	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Catania		Italy	95100
34	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Lecce		Italy	73100
35	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Padova		Italy	35128
36	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Perugia		Italy	06100
37	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Ravenna		Italy	48100
38	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Hokkaido		Japan	060-0002
39	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kanagawa		Japan	235-0045
40	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kumamoto		Japan	862-0976
41	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Tokyo		Japan	162-8666
42	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Guadalajara Jalisco		Mexico	04460
43	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Guadalajara		Mexico	44150
44	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Monterrey		Mexico	64460
45	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Katowice		Poland	40-057
46	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Lodz		Poland	93-338
47	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Poznan		Poland	61-655
48	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Warsaw		Poland	01-192
49	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Arkhangelsk		Russian Federation	163045
50	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Moscow		Russian Federation	119991
51	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Saint Petersburg		Russian Federation	193257

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: 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), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01481779
• Other Study ID Numbers: 12146; I2R-MC-BIAN; 2011-001261-40
• First Posted: Nov 30, 2011
• Last Update Posted: Apr 17, 2018
• Last Verified: Mar 1, 2018

• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1; Insulin Lispro

Study Results

Participant Flow

Arm/Group Title	LY2605541 + Insulin Lispro	Glargine + Insulin Lispro
Arm/Group Description	LY2605541 titrated based on blood glucose readings, administered by subcutaneous (SC) injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.	Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
Period Title: Overall Study
STARTED	295	160
Received at Least 1 Dose of Study Drug	294	159
COMPLETED	225	132
NOT COMPLETED	70	28

Baseline Characteristics

Arm/Group Title	LY2605541 + Insulin Lispro	Glargine + Insulin Lispro	Total
Arm/Group Description	LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.	Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.	Total of all reporting groups
Overall Participants	295	160	455
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39.68 (12.93)	38.91 (14.10)	39.41 (13.34)
Sex: Female, Male (Count of Participants)
Female	157 53.2%	73 45.6%	230 50.5%
Male	138 46.8%	87 54.4%	225 49.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	33 11.2%	16 10%	49 10.8%
Not Hispanic or Latino	153 51.9%	85 53.1%	238 52.3%
Unknown or Not Reported	109 36.9%	59 36.9%	168 36.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	6 2%	3 1.9%	9 2%
Asian	63 21.4%	31 19.4%	94 20.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	5 1.7%	0 0%	5 1.1%
White	221 74.9%	125 78.1%	346 76%
More than one race	0 0%	1 0.6%	1 0.2%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
France	23 7.8%	14 8.8%	37 8.1%
United States	85 28.8%	45 28.1%	130 28.6%
Mexico	25 8.5%	15 9.4%	40 8.8%
Poland	27 9.2%	14 8.8%	41 9%
Austria	7 2.4%	4 2.5%	11 2.4%
Russia	11 3.7%	9 5.6%	20 4.4%
Germany	45 15.3%	21 13.1%	66 14.5%
Japan	60 20.3%	31 19.4%	91 20%
Italy	12 4.1%	7 4.4%	19 4.2%

Outcome Measures

1. Primary Outcome

Title	Hemoglobin A1c (HbA1c) at 26 Weeks
Description	HbA1c is a test that measures a participant's average blood glucose level over a 2- to 3-month timeframe. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM), adjusting for treatment, stratification factors (baseline low-density lipoprotein cholesterol [LDL-C] [<100 milligrams per deciliter (mg/dL) and ≥100 mg/dL] and country), visit, treatment-by-visit interaction, and baseline HbA1c as the fixed effects and participant as the random effect.
Time Frame	26 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized, had at least 1 dose of study medication, and had evaluable HbA1c data at both baseline and post-baseline.

Arm/Group Title	LY2605541 + Insulin Lispro	Glargine + Insulin Lispro
Arm/Group Description	LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.	Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
Measure Participants	287	153
Least Squares Mean (Standard Error) [percentage of HbA1c]	7.06 (0.04)	7.43 (0.06)

2. Secondary Outcome

Title	Hemoglobin A1c (HbA1c)
Description	HbA1c is a test that measures a participant's average blood glucose level over a 2- to 3-month timeframe. LS means were calculated using MMRM, adjusting for treatment, stratification factors (baseline LDL-C [<100 mg/dL and ≥100 mg/dL] and country), visit, treatment-by-visit interaction, and baseline HbA1c as the fixed effects.
Time Frame	52 weeks and 78 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized, had at least 1 dose of study medication, and had evaluable HbA1c data at both baseline and post-baseline.

Arm/Group Title	LY2605541 + Insulin Lispro	Glargine + Insulin Lispro
Arm/Group Description	LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.	Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
Measure Participants	287	153
Week 52	7.30 (0.05)	7.55 (0.06)
Week 78	7.43 (0.05)	7.70 (0.07)

3. Secondary Outcome

Title	Change From Baseline in Hemoglobin A1c (HbA1c)
Description	HbA1c is a test that measures a participant's average blood glucose level over a 2- to 3-month timeframe. LS means were calculated using MMRM, adjusting for treatment, stratification factors (baseline LDL-C [<100 mg/dL and ≥100 mg/dL] and country), visit, treatment-by-visit interaction, and baseline HbA1c as the fixed effects.
Time Frame	Baseline, 26 weeks, 52 weeks, 78 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized, had at least 1 dose of study medication, and had evaluable HbA1c data at both baseline and post-baseline.

Arm/Group Title	LY2605541 + Insulin Lispro	Glargine + Insulin Lispro
Arm/Group Description	LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.	Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
Measure Participants	287	153
Week 26	-0.69 (0.04)	-0.33 (0.06)
Week 56	-0.46 (0.05)	-0.21 (0.06)
Week 78	-0.33 (0.05)	-0.05 (0.07)

4. Secondary Outcome

Title	Percentage of Participants With Hemoglobin A1c (HbA1c) Less Than 7.0% or Less Than or Equal to 6.5% Using Last Observation Carried Forward (LOCF)
Description	HbA1c is a test that measures a participant's average blood glucose level over a 2- to 3-month timeframe. The percentage of participants was calculated by dividing the number of participants reaching target HbA1c by the total number of participants analyzed, then multiplying by 100.
Time Frame	26 weeks and 52 weeks and 78 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized, had at least 1 dose of study medication, and had evaluable HbA1c data. Missing endpoints were imputed with the LOCF method, using only post-baseline data.

Arm/Group Title	LY2605541 + Insulin Lispro	Glargine + Insulin Lispro
Arm/Group Description	LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.	Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
Measure Participants	287	153
HbA1c ≤6.5%, Week 26	28.6 9.7%	13.7 8.6%
HbA1c ≤6.5%, Week 52	23.3 7.9%	13.1 8.2%
HbA1c ≤6.5%, Week 78	20.2 6.8%	13.1 8.2%
HbA1c <7.0%, Week 26	44.9 15.2%	27.5 17.2%
HbA1c <7.0%, Week 52	37.3 12.6%	28.1 17.6%
HbA1c <7.0%, Week 78	34.5 11.7%	22.9 14.3%

5. Secondary Outcome

Title	Proportion of Participants With Hemoglobin A1c (HbA1c) Less Than 7.0% Without Nocturnal Hypoglycemia
Description	Hypoglycemic episodes are defined as an event that is associated with reported signs and symptoms of hypoglycemia and/or a documented blood glucose concentration of ≤70 mg/dL (3.9 millimoles per liter [mmol/L]). A nocturnal hypoglycemic event occurred between bedtime and waking and between the time points of 10:00 PM and 10:00 AM. The percentage of participants was calculated by dividing the number of participants with HbA1c <7.0% without nocturnal hypoglycemia by the total number of participants analyzed, then multiplying by 100.
Time Frame	26 weeks and 52 weeks and 78 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized, had at least 1 dose of study medication, and had evaluable data. Missing endpoints were imputed with the LOCF method.

Arm/Group Title	LY2605541 + Insulin Lispro	Glargine + Insulin Lispro
Arm/Group Description	LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.	Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
Measure Participants	287	153
Week 26	3.8 1.3%	2.0 1.3%
Week 52	2.1 0.7%	0.7 0.4%
Week 78	1.0 0.3%	0.0 0%

6. Secondary Outcome

Title	Total Hypoglycemia Rates (Adjusted by 30 Days)
Description	Hypoglycemic episodes are defined as events that are associated with reported signs and symptoms of hypoglycemia and/or documented blood glucose (BG) concentrations of ≤70 mg/dL (3.9 mmol/L). Group mean rates of total hypoglycemia (per 30 days) are presented and were calculated from negative binomial regression models (number of episodes = treatment + baseline total hypoglycemia rate, with log [exposure in days/30] as an offset variable). Group mean is estimated by taking the inverse link function on individual participant covariates first and then averages over all participants.
Time Frame	Baseline through 26 weeks and Baseline through 52 weeks and Baseline through 78 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized, had at least 1 dose of study medication, and had evaluable data at both baseline and post-baseline.

Arm/Group Title	LY2605541 + Insulin Lispro	Glargine + Insulin Lispro
Arm/Group Description	LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.	Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
Measure Participants	293	159
Baseline-Week 26	16.01 (0.44)	12.43 (0.55)
Baseline-Week 52	14.84 (0.42)	11.75 (0.55)
Baseline-Week 78	14.33 (0.42)	11.43 (0.55)

7. Secondary Outcome

Title	Percentage of Participants With Total Hypoglycemia Events
Description	Hypoglycemic events are defined as events that are associated with reported signs and symptoms of hypoglycemia and/or documented BG concentrations of ≤70 mg/dL (3.9 mmol/L). The percentage of participants was calculated by dividing the number of participants with hypoglycemic episodes by the total number of participants analyzed, then multiplying by 100.
Time Frame	Baseline through 26 weeks and Baseline through 52 weeks and Baseline through 78 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized, had at least 1 dose of study medication, and had evaluable data at both baseline and post-baseline.

Arm/Group Title	LY2605541 + Insulin Lispro	Glargine + Insulin Lispro
Arm/Group Description	LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.	Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
Measure Participants	294	159
Baseline-Week 26	99.0 33.6%	96.9 60.6%
Baseline-Week 52	99.0 33.6%	96.9 60.6%
Baseline-Week 78	99.0 33.6%	96.9 60.6%

8. Secondary Outcome

Title	Nocturnal Hypoglycemia Rates (Adjusted by 30 Days)
Description	Hypoglycemic episodes are defined as events that are associated with reported signs and symptoms of hypoglycemia and/or a documented BG concentration of ≤70 mg/dL (3.9 mmol/L). A nocturnal hypoglycemic event occurred between bedtime and waking and between the time points of 10:00 PM and 10:00 AM. Group mean rates of nocturnal hypoglycemia (per 30 days) are presented and were calculated from negative binomial regression models (number of episodes = treatment + baseline nocturnal hypoglycemia rate, with log [exposure in days/30] as an offset variable). Group mean is estimated by taking the inverse link function on individual participant covariates first and then averages over all participants.
Time Frame	Baseline through 26 weeks and Baseline through 52 weeks and Baseline through 78 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized, had at least 1 dose of study medication, and had evaluable data at both baseline and post-baseline.

Arm/Group Title	LY2605541 + Insulin Lispro	Glargine + Insulin Lispro
Arm/Group Description	LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.	Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
Measure Participants	293	159
Baseline-Week 26	1.69 (0.12)	2.66 (0.19)
Baseline-Week 52	1.63 (0.11)	2.45 (0.19)
Baseline-Week 78	1.58 (0.11)	2.28 (0.17)

9. Secondary Outcome

Title	Percentage of Participants With Nocturnal Hypoglycemic Events
Description	Hypoglycemic episodes are defined as an event that is associated with reported signs and symptoms of hypoglycemia and/or a BG concentration of ≤70 mg/dL (3.9 mmol/L). A nocturnal hypoglycemic event occurred between bedtime and waking and between the time points of 10:00 PM and 10:00 AM. The percentage of participants was calculated by dividing the number of participants with nocturnal hypoglycemic episodes by the total number of participants analyzed, then multiplying by 100.
Time Frame	Baseline through 26 weeks and Baseline through 52 weeks and Baseline through 78 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized, had at least 1 dose of study medication, and had evaluable data at both baseline and post-baseline.

Arm/Group Title	LY2605541 + Insulin Lispro	Glargine + Insulin Lispro
Arm/Group Description	LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.	Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
Measure Participants	294	159
Baseline-Week 26	87.4 29.6%	90.6 56.6%
Baseline-Week 52	91.5 31%	91.8 57.4%
Baseline-Week 78	93.5 31.7%	92.5 57.8%

10. Secondary Outcome

Title	Fasting Serum Glucose (FSG) by Laboratory Measurement
Description	LS means were calculated using MMRM, adjusting for treatment, stratification factors (baseline HbA1c [≤8.5% and >8.5%], baseline LDL-C level [<100 mg/dL and ≥100 mg/dL], and country), visit, treatment-by-visit interaction, and corresponding baseline dependent variable as the fixed effects, and participants as the random effect.
Time Frame	26 weeks and 52 weeks and 78 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized, had at least 1 dose of study medication, and had evaluable FSG data at both baseline and post-baseline.

Arm/Group Title	LY2605541 + Insulin Lispro	Glargine + Insulin Lispro
Arm/Group Description	LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.	Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
Measure Participants	285	152
Week 26	138.22 (3.80)	160.35 (5.06)
Week 52	146.55 (4.42)	164.28 (5.72)
Week 78	144.64 (4.53)	164.78 (5.81)

11. Secondary Outcome

Title	Fasting Blood Glucose (FBG) Intra-participant Variability
Description	FBG was measured by self-monitored blood glucose (SMBG). Between-day glucose variability is measured by the standard deviation of FBG. LS means were calculated using MMRM, adjusting for treatment, stratification factors (baseline HbA1c [≤8.5% and >8.5%], baseline LDL-C level [<100 mg/dL and ≥100 mg/dL], and country), visit, treatment-by-visit interaction, and corresponding baseline dependent variable as the fixed effects, and participants as the random effect.
Time Frame	26 weeks and 52 weeks and 78 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized, had at least 1 dose of study medication, and had evaluable FBG data at both baseline and post-baseline.

Arm/Group Title	LY2605541 + Insulin Lispro	Glargine + Insulin Lispro
Arm/Group Description	LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.	Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
Measure Participants	282	153
Week 26	52.49 (1.79)	59.25 (2.43)
Week 52	53.44 (1.85)	58.15 (2.43)
Week 78	54.87 (2.20)	60.66 (2.79)

12. Secondary Outcome

Title	0300-hour Blood Glucose (BG) to Fasting Blood (FBG) Glucose Excursion
Description	Results of a 0300-hour to pre-morning meal (FBG) excursion are presented (only SMBG profiles with both 0300 hours and the next day pre-morning measurements are included for the calculation of such excursion). LS means were calculated using MMRM, adjusting for treatment, stratification factors (baseline HbA1c [≤8.5% and >8.5%], baseline LDL-C level [<100 mg/dL and ≥100 mg/dL], and country), visit, treatment-by-visit interaction, and corresponding baseline dependent variable as the fixed effects and participants as the random effect.
Time Frame	26 weeks and 52 weeks and 78 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized, had at least 1 dose of study medication, and had evaluable SMBG data at baseline and post-baseline.

Arm/Group Title	LY2605541 + Insulin Lispro	Glargine + Insulin Lispro
Arm/Group Description	LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.	Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
Measure Participants	209	112
Week 26	-9.92 (6.24)	-14.08 (8.75)
Week 52	-6.15 (6.91)	-9.02 (9.58)
Week 78	-10.82 (8.25)	-28.94 (10.50)

13. Secondary Outcome

Title	9 Point Self-monitored Blood Glucose (SMBG)
Description	9-point SMBG profiles were obtained over 2 days within the week prior to Weeks 0, 4, 12, 26, 39, 52, 65, and 78. SMBG measurements were taken at 9 time points: pre-morning meal, 2 hours post-morning meal, pre-midday meal, 2 hours post-midday meal, pre-evening meal, 2 hours post-evening meal, bedtime, at approximately 0300 hours, and the pre-morning meal the next day. LS means were calculated using MMRM, adjusting for treatment, stratification factors (baseline HbA1c [≤8.5% and >8.5%], baseline LDL-C level [<100 mg/dL and ≥100 mg/dL], and country), visit, treatment-by-visit interaction, and corresponding baseline dependent variable as the fixed effects and participants as the random effect.
Time Frame	26 weeks and 52 weeks and 78 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized, had at least 1 dose of study medication, and had evaluable SMBG data at both baseline and post-baseline.

Arm/Group Title	LY2605541 + Insulin Lispro	Glargine + Insulin Lispro
Arm/Group Description	LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.	Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
Measure Participants	271	143
Pre-morning meal, Week 26	158.58 (3.82)	144.40 (5.20)
Pre-morning meal, Week 52	160.89 (4.13)	152.55 (5.38)
Pre-morning meal, Week 78	163.09 (4.66)	153.38 (5.99)
2 hours post-morning meal, Week 26	172.39 (4.59)	165.53 (6.44)
2 hours post-morning meal, Week 52	176.32 (5.61)	168.38 (7.47)
2 hours post-morning meal, Week 78	183.64 (6.23)	190.54 (7.91)
Pre-midday meal, Week 26	136.21 (3.92)	153.12 (5.33)
Pre-midday meal, Week 52	142.82 (4.27)	149.78 (5.66)
Pre-midday meal, Week 78	150.83 (4.90)	154.56 (6.33)
2 hours post-midday meal, Week 26	157.17 (4.78)	164.75 (6.69)
2 hours post-midday meal, Week 52	159.59 (5.11)	168.83 (6.94)
2 hours post-midday meal, Week 78	154.46 (5.76)	175.52 (7.51)
Pre-evening meal, Week 26	153.20 (4.29)	168.08 (5.75)
Pre-evening meal, Week 52	153.01 (5.17)	183.18 (6.81)
Pre-evening meal, Week 78	149.89 (4.92)	174.50 (6.17)
2 hours post-evening meal, Week 26	149.74 (5.17)	191.99 (7.20)
2 hours post-evening meal, Week 52	157.81 (6.79)	198.10 (9.06)
2 hours post-evening meal, Week 78	163.27 (6.07)	189.43 (7.75)
Bedtime, Week 26	151.66 (4.15)	176.17 (5.63)
Bedtime, Week 52	167.35 (5.33)	182.08 (7.11)
Bedtime, Week 78	165.63 (5.37)	185.45 (6.74)
0300 hours, Week 26	159.73 (5.30)	163.18 (7.50)
0300 hours, Week 52	157.52 (6.06)	148.26 (8.36)
0300 hours, Week 78	165.82 (7.19)	170.35 (9.02)
Pre-morning meal next day, Week 26	149.94 (3.74)	143.89 (5.10)
Pre-morning meal next day, Week 52	155.79 (4.24)	145.55 (5.59)
Pre-morning meal next day, Week 78	156.87 (4.80)	152.63 (6.11)

14. Secondary Outcome

Title	Change From Baseline in Body Weight
Description	LS means were calculated using MMRM, adjusting for treatment, stratification factors (baseline HbA1c [≤8.5% and >8.5%], baseline LDL-C level [<100 mg/dL and ≥100 mg/dL], and country), visit, treatment-by-visit interaction, and corresponding baseline dependent variable as the fixed effects, and participants as the random effect.
Time Frame	Baseline and 26 weeks and 52 weeks and 78 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized, had at least 1 dose of study medication, and had evaluable body weight data at both baseline and post-baseline.

Arm/Group Title	LY2605541 + Insulin Lispro	Glargine + Insulin Lispro
Arm/Group Description	LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.	Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
Measure Participants	287	154
Week 26	-1.17 (0.20)	0.71 (0.27)
Week 52	-1.22 (0.25)	1.00 (0.33)
Week 78	-0.93 (0.28)	1.04 (0.37)

15. Secondary Outcome

Title	Basal, Bolus, and Total Insulin Dose
Description	Basal insulin dose, short-acting bolus insulin dose (each meal and overall), and total insulin dose were calculated based on the dose during the last 7 days prior to the post-treatment visit or last 3 days prior to the randomization visit. LS means were calculated using MMRM, adjusting for treatment, stratification factors (baseline HbA1c [≤8.5% and >8.5%], baseline LDL-C level [<100 mg/dL and ≥100 mg/dL], and country), visit, treatment-by-visit interaction, and corresponding baseline dependent variable as the fixed effects and participants as the random effect.
Time Frame	26 weeks and 52 weeks and 78 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized, had at least 1 dose of study medication, and had evaluable insulin dose data.

Arm/Group Title	LY2605541 + Insulin Lispro	Glargine + Insulin Lispro
Arm/Group Description	LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.	Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
Measure Participants	282	156
Basal Insulin, Week 26	0.40 (0.01)	0.34 (0.01)
Basal Insulin, Week 52	0.40 (0.01)	0.34 (0.01)
Basal Insulin, Week 78	0.41 (0.01)	0.35 (0.01)
Bolus Insulin, Week 26	0.37 (0.01)	0.46 (0.02)
Bolus Insulin, Week 52	0.38 (0.01)	0.47 (0.02)
Bolus Insulin, Week 78	0.37 (0.02)	0.48 (0.02)
Total Insulin, Week 26	0.73 (0.02)	0.78 (0.02)
Total Insulin, Week 52	0.74 (0.02)	0.79 (0.03)
Total Insulin, Week 78	0.75 (0.02)	0.80 (0.03)

16. Secondary Outcome

Title	Lipid Profile
Description	Concentrations of cholesterol, high-density lipoprotein cholesterol (HDL-C), LDL-C, and triglycerides are summarized. LS means were calculated using MMRM, adjusting for stratification factors (baseline HbA1c [≤8.5% and >8.5%], country, LDL-C [<100 mg/dL and ≥100 mg/dL] except for the LDL-C outcome variable), visit, treatment, treatment-by-visit interaction, and baseline value of corresponding lipid outcome variable.
Time Frame	26 weeks and 52 weeks and 78 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized, had at least 1 dose of study medication, and had evaluable lipid data at both baseline and post-baseline.

Arm/Group Title	LY2605541 + Insulin Lispro	Glargine + Insulin Lispro
Arm/Group Description	LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.	Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
Measure Participants	288	152
Cholesterol, Week 26	191.86 (1.63)	187.93 (2.19)
Cholesterol, Week 52	190.72 (1.59)	188.65 (2.10)
Cholesterol, Week 78	191.78 (1.86)	190.06 (2.39)
HDL-C, Week 26	61.87 (0.59)	62.75 (0.80)
HDL-C, Week 52	61.01 (0.56)	61.46 (0.74)
HDL-C, Week 78	60.77 (0.66)	61.97 (0.85)
LDL-C, Week 26	108.85 (1.33)	108.31 (1.79)
LDL-C, Week 52	109.40 (1.39)	109.74 (1.84)
LDL-C, Week 78	109.62 (1.62)	110.35 (2.09)
Triglycerides, Week 26	109.64 (3.89)	85.35 (5.24)
Triglycerides, Week 52	105.17 (3.64)	87.94 (4.80)
Triglycerides, Week 78	110.80 (4.78)	88.96 (6.14)

17. Secondary Outcome

Title	Percentage of Participants With Change in Anti-LY2605541 Antibodies
Description	The percentage of participants with a treatment-emergent anti-LY2605541 antibody response (TEAR) is summarized. TEAR is defined as change from baseline to post-baseline in the anti-LY2605541 antibody level either from undetectable to detectable or from detectable to the value with at least 130% relative increase from baseline.
Time Frame	Baseline through 26 weeks and Baseline through 52 weeks and Baseline through 78 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized, had at least 1 dose of study medication, and had evaluable anti-LY2605541 antibody data at baseline and post-baseline. Missing endpoints were imputed with the LOCF method.

Arm/Group Title	LY2605541 + Insulin Lispro	Glargine + Insulin Lispro
Arm/Group Description	LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.	Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
Measure Participants	288	153
Week 26	30.6 10.4%	15.8 9.9%
Week 52	29.9 10.1%	17.1 10.7%
Week 78	26.4 8.9%	13.1 8.2%

18. Secondary Outcome

Title	Insulin Treatment Satisfaction Questionnaire (ITSQ)
Description	ITSQ is a validated instrument containing 22 items that assess treatment satisfaction for participants with diabetes and on insulin. The questionnaire measures satisfaction from the following 5 domains: Inconvenience of Regimen, Lifestyle Flexibility, Glycemic Control, Hypoglycemic Control, and Insulin Delivery Device. Data presented are the transformed overall score on a scale of 0-100, where higher scores indicate better treatment satisfaction. LS means were calculated using an analysis of covariance (ANCOVA) model with treatment and stratification (baseline HbA1c [≤8.5% or >8.5%] and country) as fixed effects and baseline value of the dependent variable as a covariate.
Time Frame	26 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized, had at least 1 dose of study medication, and had evaluable ITSQ data at both baseline and post-baseline. Missing endpoints were imputed with the LOCF method.

Arm/Group Title	LY2605541 + Insulin Lispro	Glargine + Insulin Lispro
Arm/Group Description	LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.	Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
Measure Participants	273	149
Least Squares Mean (Standard Error) [units on a scale]	72.43 (0.69)	73.91 (0.94)

19. Secondary Outcome

Title	Low Blood Sugar Survey (LBSS)
Description	LBSS (also referenced as Hypoglycemia Fear Survey - II [HFS-II]) is a 33-item questionnaire that measures 1) behaviors to avoid hypoglycemia and its negative consequences (15 items) and 2) worries about hypoglycemia and its negative consequences (18 items). Responses are made on a 5-point Likert scale where 0 = Never and 4 = Always. Total score is the sum of all items (range 0-132). Higher total scores reflect greater fear of hypoglycemia. LS means were calculated using MMRM, adjusting for treatment, stratification factors (baseline HbA1c [≤8.5% and >8.5%] and country), visit, treatment-by-visit interaction , and corresponding baseline dependent variable as the fixed effects and participants as the random effect.
Time Frame	26 weeks and 52 weeks and 78 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized, had at least 1 dose of study medication, and had evaluable LBSS data at both baseline and post-baseline.

Arm/Group Title	LY2605541 + Insulin Lispro	Glargine + Insulin Lispro
Arm/Group Description	LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.	Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
Measure Participants	287	151
Week 26	28.09 (0.70)	27.09 (0.95)
Week 52	27.76 (0.77)	27.00 (1.01)
Week 78	27.68 (0.91)	27.14 (1.18)

20. Secondary Outcome

Title	European Quality of Life-5 Dimension (EQ-5D)
Description	The EQ-5D is a generic, multidimensional, health-related, quality-of-life instrument. The profile allows participants to rate their health state in 5 health domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) using a 3-level scale of 1-3 (no problem, some problems, and extreme problems). These combinations of attributes are converted into a weighted health-state Index Score according to the United States population-based algorithm. Scores range from -0.11 to 1.0, where a score of 1.0 indicates perfect health. LS means were calculated using ANCOVA, adjusting for treatment and stratification factors (baseline HbA1c [≤8.5% or >8.5%] and country) as fixed effects and baseline EQ-5D score as a covariate.
Time Frame	26 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized, had at least 1 dose of study medication, and had evaluable EQ-5D data at both baseline and post-baseline. Missing endpoints were imputed with the LOCF method.

Arm/Group Title	LY2605541 + Insulin Lispro	Glargine + Insulin Lispro
Arm/Group Description	LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.	Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
Measure Participants	277	150
Least Squares Mean (Standard Error) [units on a scale]	0.92 (0.01)	0.91 (0.01)

21. Secondary Outcome

Title	Rapid Assessment of Physical Activity (RAPA)
Description	The RAPA questionnaire assesses the level and intensity of physical activity of adult participants. It contains 2 subscales: RAPA 1 (Aerobic) and RAPA 2 (Strength and Flexibility). RAPA 1 contains 7 questions regarding the participant's amount and intensity of physical activity, allowing each participant's aerobic activity level to be categorized as sedentary, underactive, light activities, light activity, regular underactive, or active. RAPA 2 contains 2 questions regarding participants' physical activities that increase strength and improve flexibility. Each participant's strength and flexibility activity level is then categorized as neither strength nor flexibility (flex) activity, either strength or flex (not both), both strength and flex activity. The percentage of participants in each RAPA 1/2 category is presented and was calculated by dividing the number of participants in each RAPA 1/2 category by the total number of participants analyzed, then multiplying by 100.
Time Frame	26 weeks and 78 weeks

Outcome Measure Data

Analysis Population Description

Participants who were randomized, had at least 1 dose of study medication, and had evaluable RAPA data. Missing endpoints were imputed with the LOCF method, using only post-baseline data.

Arm/Group Title	LY2605541 + Insulin Lispro	Glargine + Insulin Lispro
Arm/Group Description	LY2605541 titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.	Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
Measure Participants	98	57
RAPA 1, Sedentary, Week 26	1.0 0.3%	0.0 0%
RAPA 1, Sedentary, Week 78	1.3 0.4%	0.0 0%
RAPA 1, Underactive, Week 26	3.1 1.1%	3.5 2.2%
RAPA 1, Underactive, Week 78	3.8 1.3%	2.0 1.3%
RAPA 1, Light activity, Week 26	13.3 4.5%	10.5 6.6%
RAPA 1, Light activity, Week 78	7.5 2.5%	13.7 8.6%
RAPA 1, Regular underactive, Week 26	24.5 8.3%	29.8 18.6%
RAPA 1, Regular underactive, Week 78	31.3 10.6%	29.4 18.4%
RAPA 1, Active, Week 26	58.2 19.7%	56.1 35.1%
RAPA 1, Active, Week 78	56.3 19.1%	54.9 34.3%
RAPA 2, Neither strength/flex, Week 26	35.7 12.1%	43.9 27.4%
RAPA 2, Neither strength/flex, Week 78	37.0 12.5%	47.1 29.4%
RAPA 2, Either strength/flex, Week 26	30.6 10.4%	35.1 21.9%
RAPA 2, Either strength/flex, Week 78	33.3 11.3%	29.4 18.4%
RAPA 2, Both strength/flex, Week 26	33.7 11.4%	21.1 13.2%
RAPA 2, Both strength/flex, Week 78	29.6 10%	23.5 14.7%

Adverse Events

Arm/Group Title	LY2605541 + Insulin Lispro		Glargine + Insulin Lispro
Arm/Group Description	LY2605541 titrated based on blood glucose readings, administered by subcutaneous (SC) injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro titrated based on blood glucose readings, administered subcutaneously via pen device at meal times for 78 weeks.		Glargine dose titrated based on blood glucose readings, administered by SC injection via pen device once daily at bedtime for 78 weeks in combination with Insulin Lispro. Insulin Lispro dose titrated based on blood glucose readings, administered by SC injection via pen device at meal times for 78 weeks.
All Cause Mortality
	LY2605541 + Insulin Lispro		Glargine + Insulin Lispro
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	LY2605541 + Insulin Lispro		Glargine + Insulin Lispro
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	67/294 (22.8%)		25/159 (15.7%)
Cardiac disorders
Atrial fibrillation	3/294 (1%)	4	1/159 (0.6%)	1
Cardiomyopathy	0/294 (0%)	0	1/159 (0.6%)	4
Ear and labyrinth disorders
Sudden hearing loss	0/294 (0%)	0	1/159 (0.6%)	1
Tympanic membrane perforation	1/294 (0.3%)	1	0/159 (0%)	0
Gastrointestinal disorders
Faeces pale	1/294 (0.3%)	1	0/159 (0%)	0
Impaired gastric emptying	0/294 (0%)	0	1/159 (0.6%)	2
Pancreatitis	2/294 (0.7%)	2	0/159 (0%)	0
Pancreatitis acute	1/294 (0.3%)	1	0/159 (0%)	0
Small intestinal perforation	1/294 (0.3%)	1	0/159 (0%)	0
Hepatobiliary disorders
Hepatic function abnormal	1/294 (0.3%)	1	0/159 (0%)	0
Immune system disorders
Anaphylactic shock	1/294 (0.3%)	1	0/159 (0%)	0
Infections and infestations
Abscess limb	1/294 (0.3%)	1	0/159 (0%)	0
Cellulitis	1/294 (0.3%)	2	0/159 (0%)	0
Chronic sinusitis	1/294 (0.3%)	3	0/159 (0%)	0
Diabetic gangrene	0/294 (0%)	0	1/159 (0.6%)	1
Gastroenteritis	2/294 (0.7%)	2	0/159 (0%)	0
Infectious mononucleosis	1/294 (0.3%)	2	0/159 (0%)	0
Osteomyelitis	2/294 (0.7%)	4	1/159 (0.6%)	3
Pneumonia	0/294 (0%)	0	1/159 (0.6%)	1
Pneumonia bacterial	1/294 (0.3%)	1	0/159 (0%)	0
Post procedural sepsis	0/294 (0%)	0	1/159 (0.6%)	1
Pseudomonas infection	1/294 (0.3%)	1	0/159 (0%)	0
Sepsis	0/294 (0%)	0	1/159 (0.6%)	1
Staphylococcal sepsis	0/294 (0%)	0	1/159 (0.6%)	1
Injury, poisoning and procedural complications
Alcohol poisoning	1/294 (0.3%)	1	0/159 (0%)	0
Clavicle fracture	0/294 (0%)	0	1/159 (0.6%)	1
Fall	0/294 (0%)	0	1/159 (0.6%)	1
Incorrect dose administered	1/294 (0.3%)	1	0/159 (0%)	0
Intentional overdose	1/294 (0.3%)	1	0/159 (0%)	0
Lower limb fracture	1/294 (0.3%)	1	0/159 (0%)	0
Overdose	1/294 (0.3%)	1	0/159 (0%)	0
Road traffic accident	1/294 (0.3%)	1	0/159 (0%)	0
Tibia fracture	0/294 (0%)	0	1/159 (0.6%)	1
Metabolism and nutrition disorders
Diabetic ketoacidosis	1/294 (0.3%)	1	1/159 (0.6%)	1
Hypoglycaemia	45/294 (15.3%)	73	13/159 (8.2%)	20
Hyponatraemia	0/294 (0%)	0	1/159 (0.6%)	1
Ketoacidosis	1/294 (0.3%)	1	0/159 (0%)	0
Metabolic disorder	1/294 (0.3%)	1	0/159 (0%)	0
Musculoskeletal and connective tissue disorders
Intervertebral disc degeneration	1/294 (0.3%)	2	0/159 (0%)	0
Intervertebral disc protrusion	1/294 (0.3%)	1	1/159 (0.6%)	1
Lumbar spinal stenosis	1/294 (0.3%)	2	0/159 (0%)	0
Muscle contracture	0/294 (0%)	0	1/159 (0.6%)	1
Spondylolisthesis	1/294 (0.3%)	2	0/159 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia	0/294 (0%)	0	1/159 (0.6%)	1
Basal cell carcinoma	1/294 (0.3%)	1	0/159 (0%)	0
Benign bone neoplasm	1/294 (0.3%)	1	0/159 (0%)	0
Breast cancer	0/294 (0%)	0	1/159 (0.6%)	1
Cervix carcinoma	1/157 (0.6%)	1	0/73 (0%)	0
Fibroadenoma of breast	1/294 (0.3%)	1	0/159 (0%)	0
Uterine leiomyoma	2/157 (1.3%)	5	0/73 (0%)	0
Nervous system disorders
Complicated migraine	0/294 (0%)	0	1/159 (0.6%)	1
Dizziness	0/294 (0%)	0	1/159 (0.6%)	1
Hypoglycaemic coma	1/294 (0.3%)	3	0/159 (0%)	0
Psychiatric disorders
Adjustment disorder	1/294 (0.3%)	3	0/159 (0%)	0
Suicide attempt	1/294 (0.3%)	1	0/159 (0%)	0
Renal and urinary disorders
Renal failure acute	0/294 (0%)	0	1/159 (0.6%)	1
Urinary incontinence	1/294 (0.3%)	1	0/159 (0%)	0
Reproductive system and breast disorders
Cervical polyp	1/157 (0.6%)	2	0/73 (0%)	0
Menorrhagia	1/157 (0.6%)	2	0/73 (0%)	0
Ovarian cyst	1/157 (0.6%)	2	0/73 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	0/294 (0%)	0	1/159 (0.6%)	1
Pulmonary embolism	1/294 (0.3%)	1	0/159 (0%)	0
Pulmonary oedema	0/294 (0%)	0	1/159 (0.6%)	1
Skin and subcutaneous tissue disorders
Skin ulcer	2/294 (0.7%)	5	0/159 (0%)	0
Surgical and medical procedures
Hysterectomy	1/157 (0.6%)	1	0/73 (0%)	0
Toe amputation	0/294 (0%)	0	1/159 (0.6%)	1
Vascular disorders
Intermittent claudication	0/294 (0%)	0	1/159 (0.6%)	1
Peripheral arterial occlusive disease	1/294 (0.3%)	2	0/159 (0%)	0
Peripheral artery stenosis	0/294 (0%)	0	1/159 (0.6%)	1
Other (Not Including Serious) Adverse Events
	LY2605541 + Insulin Lispro		Glargine + Insulin Lispro
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	256/294 (87.1%)		112/159 (70.4%)
Gastrointestinal disorders
Diarrhoea	13/294 (4.4%)	15	3/159 (1.9%)	3
Infections and infestations
Bronchitis	11/294 (3.7%)	12	4/159 (2.5%)	4
Cystitis	9/294 (3.1%)	10	3/159 (1.9%)	3
Gastroenteritis	11/294 (3.7%)	11	8/159 (5%)	9
Gastroenteritis viral	4/294 (1.4%)	4	5/159 (3.1%)	6
Influenza	25/294 (8.5%)	32	14/159 (8.8%)	14
Nasopharyngitis	92/294 (31.3%)	152	38/159 (23.9%)	61
Pharyngitis	13/294 (4.4%)	19	7/159 (4.4%)	9
Upper respiratory tract infection	13/294 (4.4%)	22	12/159 (7.5%)	17
Urinary tract infection	15/294 (5.1%)	17	8/159 (5%)	14
Investigations
Alanine aminotransferase increased	12/294 (4.1%)	20	1/159 (0.6%)	1
Weight increased	4/294 (1.4%)	4	6/159 (3.8%)	6
Musculoskeletal and connective tissue disorders
Back pain	15/294 (5.1%)	17	7/159 (4.4%)	7
Nervous system disorders
Headache	18/294 (6.1%)	27	10/159 (6.3%)	13
Psychiatric disorders
Depression	2/294 (0.7%)	2	5/159 (3.1%)	5
Respiratory, thoracic and mediastinal disorders
Cough	9/294 (3.1%)	12	5/159 (3.1%)	6
Skin and subcutaneous tissue disorders
Lipodystrophy acquired	17/294 (5.8%)	24	1/159 (0.6%)	1
Lipohypertrophy	45/294 (15.3%)	66	0/159 (0%)	0
Vascular disorders
Hypertension	10/294 (3.4%)	10	1/159 (0.6%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.