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IMAGINE 4: A Study in Participants With Type 2 Diabetes Mellitus

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT01468987
Collaborator
(none)
1,369
Enrollment
156
Locations
2
Arms
20
Duration (Months)
8.8
Patients Per Site
0.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is:

  • To compare blood glucose (blood sugar) control on LY2605541 with insulin glargine after 26 weeks of treatment.

  • To compare the rate of night time hypoglycemia (low blood glucose) on LY2605541 with insulin glargine during 26 weeks of treatment.

  • To compare the number of participants on LY2605541 reaching blood glucose targets without hypoglycemia episodes at night to those taking insulin glargine after 26 weeks of treatment.

  • To compare the rate of hypoglycemia over a 24-hour period on LY2605541 with insulin glargine during 26 weeks of treatment.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
1369 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
The Impact of LY2605541 Versus Insulin Glargine for Patients With Type 2 Diabetes Mellitus Advanced to Multiple Injection Bolus Insulin With Insulin Lispro: a Double-Blind, Randomized, 26-week Study - The IMAGINE 4 Study
Study Start Date :
Dec 1, 2011
Actual Primary Completion Date :
Aug 1, 2013
Actual Study Completion Date :
Aug 1, 2013

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Insulin Glargine + Insulin Lispro

Participant-specific dose of Insulin Glargine will be administered subcutaneously (SC) once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro will be administered SC for preprandial (pre-meal) and supplemental doses for 26 weeks.

Drug: Insulin Glargine

Drug: Insulin Lispro
Other Names:
  • Humalog

    		•
    Experimental: LY2605541 + Insulin Lispro

    Participant-specific dose of LY2605541 will be administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro will be administered SC for preprandial and supplemental doses for 26 weeks.

    Drug: LY2605541
    Other Names:
  • Insulin Peglispro

    • Drug: Insulin Lispro
    Other Names:
  • Humalog

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Change From Baseline in Hemoglobin A1c (HbA1c) at 26 Weeks [Baseline, 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 stratification factors (country, low-density lipoprotein cholesterol [LDL-C, <100 milligrams per deciliter (mg/dL) and ≥100 mg/dL], and number of insulin injections at baseline [1, 2, or ≥3]), visit, treatment, visit-by-treatment interaction, and baseline HbA1c.

    Secondary Outcome Measures

    1. Total Hypoglycemia Rates (Adjusted for 30 Days) [Baseline through 26 weeks]

      Hypoglycemic episodes are defined as events which are associated with reported signs and symptoms of hypoglycemia and/or documented blood glucose (BG) concentrations of ≤70 mg/dL (3.9 millimoles per liter [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.

    2. Percentage of Participants With Total Hypoglycemia Episodes [Baseline through 26 weeks]

      Hypoglycemic episodes are defined as events which 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, multiplied by 100.

    3. Nocturnal Hypoglycemia Rates (Adjusted for 30 Days) [Baseline through 26 weeks]

      Hypoglycemic episodes are defined as events which 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.

    4. Percentage of Participants With Nocturnal Hypoglycemia Episodes [Baseline through 26 weeks]

      Hypoglycemic episodes are defined as an event which 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, multiplied by 100.

    5. Body Weight Change From Baseline to 26 Weeks [Baseline, 26 weeks]

      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], and number of insulin injections at baseline [1, 2, or ≥3]), treatment, visit, treatment-by-visit interaction, and baseline body weight as fixed effects, and participant as a random effect.

    6. Self-Monitored Blood Glucose (SMBG) 9-point Profiles at 26 Weeks [26 weeks]

      9-point SMBG profiles were obtained over 2 nonconsecutive days within the week prior to Weeks 0, 4, 12, and 26. 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 subsequent morning prior to the morning meal. 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], and number of insulin injections at baseline [1, 2, or ≥3]), visit, treatment, visit-by-treatment interaction, and baseline BG values.

    7. Percentage of Participants With HbA1c <7.0% and ≤6.5% at 26 Weeks [up to 26 weeks]

      The percentage of participants was calculated by dividing the number of participants reaching target HbA1c by the total number of participants analyzed, multiplied by 100.

    8. Percentage of Participants With HbA1c <7.0% Without Nocturnal Hypoglycemia at 26 Weeks [up to 26 weeks]

      Hypoglycemic episodes are defined as an event which is associated with reported signs and symptoms of hypoglycemia and/or a documented blood glucose 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 HbA1c <7.0% without nocturnal hypoglycemia by the total number of participants analyzed, multiplied by 100.

    9. Basal, Bolus, and Total Insulin Dose by Weight at 26 Weeks [26 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 a constrained Longitudinal Data Analysis (cLDA) model adjusting for indicator variables of each treatment group at each post-baseline visit and stratification variables (baseline HbA1c [≤8.5% and >8.5%], country, baseline LDL-C [<100 mg/dL and ≥100 mg/dL], and baseline number of insulin injections [1, 2, or ≥3]).

    10. Fasting Serum Glucose (FSG) From Laboratory at 26 Weeks [26 weeks]

      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], and number of insulin injections at baseline [1, 2, or ≥3]), treatment, visit, treatment-by-visit interaction, and baseline FSG.

    11. Fasting Blood Glucose (FBG) (by SMBG) Intra-participant Variability at 26 Weeks [26 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 the stratification factors (baseline HbA1c [≤8.5% and >8.5%], country, baseline LDL-C [<100 mg/dL and ≥100 mg/dL], and number of insulin injections at baseline [1, 2, or ≥3]), treatment, visit, treatment-by-visit interaction, and baseline FBG variability.

    12. 0300-hour Blood Glucose to FBG Excursion at 26 Weeks [26 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 stratification factors (baseline HbA1c [≤8.5% and >8.5%], country, baseline LDL-C [<100 mg/dL and ≥100 mg/dL], and number of insulin injections at baseline [1, 2, or ≥3]), treatment, visit, treatment-by-visit interaction, and baseline excursion.

    13. HbA1c at 26 Weeks [26 weeks]

      HbA1c is a test that measures a participant's average blood glucose level over the past 2 to 3 months. LS means were calculated using MMRM adjusting for stratification factors (country, LDL-C [<100 mg/dL and ≥100 mg/dL], and number of insulin injections at baseline [1, 2, or ≥3]), treatment, visit, treatment, visit-by-treatment interaction, and baseline HbA1c.

    14. Lipid Profile at 26 Weeks [26 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], number of insulin injections at baseline [1, 2, or ≥3]), visit, treatment, visit-by-treatment interaction, and baseline value of corresponding lipid outcome variable.

    15. Number of Participants With Change in Anti-LY2605541 Antibodies From Baseline to 26 Weeks [Baseline through 26 weeks]

      The number 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.

    16. Insulin Treatment Satisfaction Questionnaire (ITSQ) at 26 Weeks [up to 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, 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 factors (baseline HbA1c [≤8.5% and >8.5%], country, and baseline number of insulin injections [1, 2, or ≥3]) as fixed effects and baseline value of the ITSQ scores as a covariate.

    17. Low Blood Sugar Survey (LBSS) at 26 Weeks [26 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 including stratification factors (baseline HbA1c [≤8.5% and >8.5%], country, baseline number of insulin injections [1, 2, or ≥3]), visit, treatment, visit-by-treatment interaction, and baseline LBSS score.

    18. EuroQoL-5D (EQ-5D) at 26 Weeks [up to 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 three 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, stratification factors (baseline HbA1c [≤8.5% and >8.5%], country, and baseline number of insulin injections [1, 2, or ≥ 3]), and baseline EQ-5D score.

    19. Rapid Assessment of Physical Activity (RAPA) at 26 Weeks [up to 26 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 activity, either strength or flexibility activity (not both), both strength and flexibility 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, multiplied 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 type 2 diabetes mellitus based on the World Health Organization (WHO) classification

    • Had diabetes ≥1 year

    • Have a hemoglobin A1c (HbA1c) value ≥7.0% and <12.0% at screening

    • Have a body mass index (BMI) ≤45.0 kilograms per square meter (kg/m^2)

    • Participants on any glucose lowering regimen that contains at least 1 daily insulin injection

    • This inclusion criterion applies ONLY to women of childbearing potential

    • Are not breastfeeding

    • Test negative for pregnancy at screening and randomization

    • Do not intend to become pregnant during the study

    • Have practiced a reliable method of birth control 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)

    • Have access to a method of communication with the site

    • Have refrigeration in the home

    • Capable of, and willing to do the following: adhere to a multiple daily injection regimen, inject insulin with a covered vial and syringe and prefilled pen, attend some appointments in the fasting state, and perform self blood glucose monitoring and record keeping as required by this protocol, as determined by the investigator. Caregiver may be responsible for all of the above

    • Have given written informed consent to participate in this study in accordance with local regulations

    Exclusion Criteria

    • Continuous subcutaneous insulin infusion therapy prior to screening

    • Are using twice daily insulin glargine prior to screening

    • Excessive insulin resistance defined as having received a daily dose of insulin ≥2.0 units per kilogram (units/kg) at the time of pre-randomization

    • Glucagon-like peptide-1 (GLP-1) receptor agonist (eg, exenatide, exenatide once weekly, or liraglutide), thiazolidinedione (rosiglitazone, pioglitazone), or pramlintide, used concurrently or within 90 days prior to screening

    • 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 ≥90 days prior to screening

    • Have fasting hypertriglyceridemia (defined as >4.5 millimoles per liter [mmol/L], >400 milligrams per deciliter [mg/dL]) at screening

    • Are currently taking, or have taken within the 90 days preceding screening, prescription or over-the-counter medications for weight loss

    • Have had any episode of severe hypoglycemia (defined as requiring assistance due to neurologically disabling hypoglycemia) within 6 months prior to entry into the study

    • Have had 2 or more emergency room visits or hospitalizations due to poor glucose control within the 6 months prior to screening

    • Have had 1 or more episodes of ketoacidosis or hyperosmolar state/coma requiring hospitalization within 6 months prior to screening

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

    • Are currently receiving renal dialysis or have a serum creatinine ≥2.0 mg/dL, except for participants taking metformin who will be required to follow local labeling restrictions regarding metformin use and serum creatinine

    • 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 ≥2X the upper limit of normal (ULN) as defined by the central laboratory, or

    • alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) >2.5X ULN as defined by the central laboratory, or

    • aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT)

    2.5X ULN as defined by the central laboratory

    • 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 increased risk for developing cancer or a recurrence of cancer in the opinion of the investigator

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

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

    • 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 had an organ transplant

    • 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. Mobile Alabama United States 36617
    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. Tucson Arizona United States 85724
    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. Little Rock Arkansas United States 72205
    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. Anaheim California United States 92801
    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. Chino California United States 91710
    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. Concord California United States 94520
    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. Fresno California United States 93720
    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. La Mesa California United States 91942
    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. Lancaster California United States 93534
    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. Mission Hills California United States 91345
    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. Tustin California United States 92780
    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. Longmont Colorado United States 80501
    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. Daytona Beach Florida United States 32117
    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. Jacksonville Florida United States 32204
    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. West Palm Beach Florida United States 33401
    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. Winter Haven Florida United States 33880
    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. Atlanta Georgia United States 30308
    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. Idaho Falls Idaho United States 83404
    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. Springfield Illinois United States 62704
    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. Des Moines Iowa United States 50314
    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. Topeka Kansas United States 66606
    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. Lexington Kentucky United States 40503
    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. Bangor Maine United States 04401
    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. Baltimore Maryland United States 21204
    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. Eagan Minnesota United States 55123
    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. Jefferson City Missouri United States 65109
    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. Saint Louis Missouri United States 63141
    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. Billings Montana United States 59101
    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. Omaha Nebraska United States 68114
    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. Las Vegas Nevada United States 89148
    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. Nashua New Hampshire United States 03063
    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. Toms River New Jersey United States 08753
    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. New York New York United States 10025
    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. Morehead City North Carolina United States 28557
    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. Fargo North Dakota United States 58103
    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. Cleveland Ohio United States 44122
    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. Columbus Ohio United States 43213
    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. Mentor Ohio United States 44060
    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. Pittsburgh Pennsylvania United States 15224
    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. Greer South Carolina United States 29651
    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. Chattanooga Tennessee United States 37411
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    89 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. Gyula Hungary 5700
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    106 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. Kaunas Lithuania LT-48259
    107 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. Klaipeda Lithuania 92304
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    115 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. Leiden Netherlands 2333 ZA
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    120 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. Wroclaw Poland 50-306
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    125 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. Yabucoa Puerto Rico 00767
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    127 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. Cluj Romania 400349
    128 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. Oradea Romania 410169
    129 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. Ploiesti Romania 100163
    130 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. Satu Mare Romania 440055
    131 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
    132 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 125367
    133 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. Rostov-On-Don Russian Federation 344022
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    135 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. Dolny Kubin Slovakia 02601
    136 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. Kosice Slovakia 04012
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    138 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. Roznava Slovakia 048 01
    139 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. Barcelona Spain 08035
    140 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. Málaga Spain 29010
    141 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. Sabadell Spain 08208
    142 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. Sevilla Spain 41010
    143 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. Seville Spain 41003
    144 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. Chiayi City Taiwan 600
    145 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. Sindian City Taiwan 23148
    146 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. Taichung Taiwan 404
    147 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. Yong Kung City Taiwan 71004
    148 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. Ankara Turkey 06100
    149 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. Diyarbakir Turkey 21280
    150 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. Istanbul Turkey 34662
    151 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. Kayseri Turkey 38039
    152 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. Kutahya Turkey 43300
    153 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. Middlesbrough Cleveland United Kingdom TS4 3BW
    154 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. Leicester Leicestershire United Kingdom LE5 4PW
    155 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. Edinburgh Scotland United Kingdom EH4 2XU
    156 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. Guildford Surrey United Kingdom GU2 7XX

    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:
    NCT01468987
    Other Study ID Numbers:
    • 12145
    • I2R-MC-BIAM
    • 2011-001254-29
    First Posted:
    Nov 10, 2011
    Last Update Posted:
    Apr 17, 2018
    Last Verified:
    Mar 1, 2018
    Additional relevant MeSH terms:
    Diabetes Mellitus
    Diabetes Mellitus, Type 2
    Insulin
    Insulin, Globin Zinc
    Insulin Glargine
    Insulin Lispro

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title LY2605541 + Insulin Lispro Insulin Glargine + Insulin Lispro
    Arm/Group Description Includes participants that were randomized to receive LY2605541 plus Insulin Lispro. Participant-specific dose of LY2605541 was administered subcutaneously (SC) once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro was administered SC for preprandial (pre-meal) and supplemental doses for 26 weeks. Includes participants that were randomized to receive Insulin Glargine plus Insulin Lispro. Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
    Period Title: Overall Study
    STARTED 691 678
    Received at Least 1 Dose of Study Drug 691 677
    COMPLETED 620 618
    NOT COMPLETED 71 60

    Baseline Characteristics

    Arm/Group Title LY2605541 + Insulin Lispro Insulin Glargine + Insulin Lispro Total
    Arm/Group Description Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks. Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks. Total of all reporting groups
    Overall Participants 691 678 1369
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    57.43
    (9.21)
    57.77
    (9.17)
    57.6
    (9.19)
    Sex: Female, Male (Count of Participants)
    Female
    315
    45.6%
    274
    40.4%
    589
    43%
    Male
    376
    54.4%
    404
    59.6%
    780
    57%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    74
    10.7%
    78
    11.5%
    152
    11.1%
    Not Hispanic or Latino
    452
    65.4%
    427
    63%
    879
    64.2%
    Unknown or Not Reported
    165
    23.9%
    173
    25.5%
    338
    24.7%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    2
    0.3%
    2
    0.3%
    4
    0.3%
    Asian
    25
    3.6%
    30
    4.4%
    55
    4%
    Native Hawaiian or Other Pacific Islander
    2
    0.3%
    2
    0.3%
    4
    0.3%
    Black or African American
    42
    6.1%
    50
    7.4%
    92
    6.7%
    White
    615
    89%
    585
    86.3%
    1200
    87.7%
    More than one race
    5
    0.7%
    9
    1.3%
    14
    1%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (Count of Participants)
    United States
    276
    39.9%
    270
    39.8%
    546
    39.9%
    Taiwan
    7
    1%
    8
    1.2%
    15
    1.1%
    Slovakia
    25
    3.6%
    17
    2.5%
    42
    3.1%
    Greece
    12
    1.7%
    11
    1.6%
    23
    1.7%
    Spain
    30
    4.3%
    35
    5.2%
    65
    4.7%
    Lithuania
    4
    0.6%
    2
    0.3%
    6
    0.4%
    Turkey
    4
    0.6%
    7
    1%
    11
    0.8%
    Austria
    9
    1.3%
    6
    0.9%
    15
    1.1%
    Russia
    19
    2.7%
    20
    2.9%
    39
    2.8%
    Israel
    20
    2.9%
    20
    2.9%
    40
    2.9%
    United Kingdom
    5
    0.7%
    3
    0.4%
    8
    0.6%
    Italy
    16
    2.3%
    16
    2.4%
    32
    2.3%
    Czechia
    23
    3.3%
    22
    3.2%
    45
    3.3%
    Hungary
    36
    5.2%
    36
    5.3%
    72
    5.3%
    Mexico
    13
    1.9%
    12
    1.8%
    25
    1.8%
    Puerto Rico
    20
    2.9%
    26
    3.8%
    46
    3.4%
    Poland
    20
    2.9%
    20
    2.9%
    40
    2.9%
    Brazil
    11
    1.6%
    13
    1.9%
    24
    1.8%
    Romania
    34
    4.9%
    31
    4.6%
    65
    4.7%
    Croatia
    5
    0.7%
    2
    0.3%
    7
    0.5%
    Denmark
    9
    1.3%
    3
    0.4%
    12
    0.9%
    Australia
    26
    3.8%
    25
    3.7%
    51
    3.7%
    Netherlands
    7
    1%
    8
    1.2%
    15
    1.1%
    Germany
    50
    7.2%
    54
    8%
    104
    7.6%
    Japan
    10
    1.4%
    11
    1.6%
    21
    1.5%

    Outcome Measures

    1. Primary Outcome
    Title Change From Baseline in 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 stratification factors (country, low-density lipoprotein cholesterol [LDL-C, <100 milligrams per deciliter (mg/dL) and ≥100 mg/dL], and number of insulin injections at baseline [1, 2, or ≥3]), visit, treatment, visit-by-treatment interaction, and baseline HbA1c.
    Time Frame Baseline, 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 Insulin Glargine + Insulin Lispro
    Arm/Group Description Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks. Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
    Measure Participants 684 672
    Least Squares Mean (Standard Error) [percentage of HbA1c]
    -1.66
    (0.04)
    -1.45
    (0.04)
    2. Secondary Outcome
    Title Total Hypoglycemia Rates (Adjusted for 30 Days)
    Description Hypoglycemic episodes are defined as events which are associated with reported signs and symptoms of hypoglycemia and/or documented blood glucose (BG) concentrations of ≤70 mg/dL (3.9 millimoles per liter [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

    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 Insulin Glargine + Insulin Lispro
    Arm/Group Description Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks. Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
    Measure Participants 689 676
    Mean (Standard Error) [episodes/participant/30 days]
    5.97
    (0.20)
    5.42
    (0.19)
    3. Secondary Outcome
    Title Percentage of Participants With Total Hypoglycemia Episodes
    Description Hypoglycemic episodes are defined as events which 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, multiplied by 100.
    Time Frame Baseline through 26 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 Insulin Glargine + Insulin Lispro
    Arm/Group Description Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks. Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
    Measure Participants 689 676
    Number [percentage of participants]
    95.2
    13.8%
    96.6
    14.2%
    4. Secondary Outcome
    Title Nocturnal Hypoglycemia Rates (Adjusted for 30 Days)
    Description Hypoglycemic episodes are defined as events which 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

    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 Insulin Glargine + Insulin Lispro
    Arm/Group Description Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks. Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
    Measure Participants 689 676
    Mean (Standard Error) [events/participant/30 days]
    0.51
    (0.03)
    0.92
    (0.05)
    5. Secondary Outcome
    Title Percentage of Participants With Nocturnal Hypoglycemia Episodes
    Description Hypoglycemic episodes are defined as an event which 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, multiplied by 100.
    Time Frame Baseline through 26 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 Insulin Glargine + Insulin Lispro
    Arm/Group Description Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks. Participant-specific dose of Insulin Glargine were administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro were administered SC for preprandial and supplemental doses for 26 weeks.
    Measure Participants 689 676
    Number [percentage of participants]
    59.5
    8.6%
    74.0
    10.9%
    6. Secondary Outcome
    Title Body Weight Change From Baseline to 26 Weeks
    Description 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], and number of insulin injections at baseline [1, 2, or ≥3]), treatment, visit, treatment-by-visit interaction, and baseline body weight as fixed effects, and participant as a random effect.
    Time Frame Baseline, 26 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 Insulin Glargine + Insulin Lispro
    Arm/Group Description Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks. Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
    Measure Participants 682 671
    Least Squares Mean (Standard Error) [kilograms (kg)]
    1.25
    (0.16)
    2.21
    (0.16)
    7. Secondary Outcome
    Title Self-Monitored Blood Glucose (SMBG) 9-point Profiles at 26 Weeks
    Description 9-point SMBG profiles were obtained over 2 nonconsecutive days within the week prior to Weeks 0, 4, 12, and 26. 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 subsequent morning prior to the morning meal. 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], and number of insulin injections at baseline [1, 2, or ≥3]), visit, treatment, visit-by-treatment interaction, and baseline BG values.
    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 SMBG data at both baseline and post-baseline.
    Arm/Group Title LY2605541 + Insulin Lispro Insulin Glargine + Insulin Lispro
    Arm/Group Description Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks. Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
    Measure Participants 639 619
    Pre-morning meal
    137.31
    (1.63)
    133.81
    (1.66)
    2 hours post-morning meal
    162.77
    (2.59)
    156.41
    (2.64)
    Pre-midday meal
    130.02
    (1.97)
    133.63
    (2.02)
    2 hours post-midday meal
    145.55
    (2.67)
    156.17
    (2.72)
    Pre-evening meal
    142.65
    (2.09)
    149.19
    (2.14)
    2 hours post-evening meal
    156.56
    (2.72)
    166.59
    (2.85)
    Bedtime
    160.15
    (2.60)
    163.62
    (2.70)
    0300 hours
    143.90
    (2.54)
    140.19
    (2.59)
    Pre-morning meal next day
    135.09
    (1.77)
    132.07
    (1.81)
    8. Secondary Outcome
    Title Percentage of Participants With HbA1c <7.0% and ≤6.5% at 26 Weeks
    Description The percentage of participants was calculated by dividing the number of participants reaching target HbA1c by the total number of participants analyzed, multiplied by 100.
    Time Frame up to 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. Missing endpoints were imputed with the last observation carried forward (LOCF) method, using only post-baseline data.
    Arm/Group Title LY2605541 + Insulin Lispro Insulin Glargine + Insulin Lispro
    Arm/Group Description Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks. Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
    Measure Participants 684 672
    HbA1c ≤6.5%
    44.4
    6.4%
    32.6
    4.8%
    HbA1c <7.0%
    63.3
    9.2%
    53.3
    7.9%
    9. Secondary Outcome
    Title Percentage of Participants With HbA1c <7.0% Without Nocturnal Hypoglycemia at 26 Weeks
    Description Hypoglycemic episodes are defined as an event which is associated with reported signs and symptoms of hypoglycemia and/or a documented blood glucose 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 HbA1c <7.0% without nocturnal hypoglycemia by the total number of participants analyzed, multiplied by 100.
    Time Frame up to 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. Missing endpoints were imputed with the LOCF method, using only post-baseline data.
    Arm/Group Title LY2605541 + Insulin Lispro Insulin Glargine + Insulin Lispro
    Arm/Group Description Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro were administered SC for preprandial and supplemental doses for 26 weeks. Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
    Measure Participants 684 672
    Number [percentage of participants]
    23.7
    3.4%
    12.2
    1.8%
    10. Secondary Outcome
    Title Basal, Bolus, and Total Insulin Dose by Weight at 26 Weeks
    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 a constrained Longitudinal Data Analysis (cLDA) model adjusting for indicator variables of each treatment group at each post-baseline visit and stratification variables (baseline HbA1c [≤8.5% and >8.5%], country, baseline LDL-C [<100 mg/dL and ≥100 mg/dL], and baseline number of insulin injections [1, 2, or ≥3]).
    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 insulin dose data.
    Arm/Group Title LY2605541 + Insulin Lispro Insulin Glargine + Insulin Lispro
    Arm/Group Description Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks. Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
    Measure Participants 615 613
    Basal Insulin
    0.68
    (0.01)
    0.60
    (0.01)
    Bolus Insulin
    0.61
    (0.02)
    0.63
    (0.02)
    Total Insulin
    1.27
    (0.02)
    1.21
    (0.02)
    11. Secondary Outcome
    Title Fasting Serum Glucose (FSG) From Laboratory at 26 Weeks
    Description 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], and number of insulin injections at baseline [1, 2, or ≥3]), treatment, visit, treatment-by-visit interaction, and baseline FSG.
    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 FSG data at both baseline and post-baseline.
    Arm/Group Title LY2605541 + Insulin Lispro Insulin Glargine + Insulin Lispro
    Arm/Group Description Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks. Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
    Measure Participants 683 672
    Least Squares Mean (Standard Error) [mg/dL]
    125.33
    (1.93)
    132.02
    (1.94)
    12. Secondary Outcome
    Title Fasting Blood Glucose (FBG) (by SMBG) Intra-participant Variability at 26 Weeks
    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 the stratification factors (baseline HbA1c [≤8.5% and >8.5%], country, baseline LDL-C [<100 mg/dL and ≥100 mg/dL], and number of insulin injections at baseline [1, 2, or ≥3]), treatment, visit, treatment-by-visit interaction, and baseline FBG variability.
    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 FBG data at both baseline and post-baseline.
    Arm/Group Title LY2605541 + Insulin Lispro Insulin Glargine + Insulin Lispro
    Arm/Group Description Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks. Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
    Measure Participants 674 652
    Least Squares Mean (Standard Error) [mg/dL]
    28.67
    (0.79)
    33.54
    (0.80)
    13. Secondary Outcome
    Title 0300-hour Blood Glucose to FBG Excursion at 26 Weeks
    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 stratification factors (baseline HbA1c [≤8.5% and >8.5%], country, baseline LDL-C [<100 mg/dL and ≥100 mg/dL], and number of insulin injections at baseline [1, 2, or ≥3]), treatment, visit, treatment-by-visit interaction, and baseline excursion.
    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 SMBG data at baseline and post-baseline.
    Arm/Group Title LY2605541 + Insulin Lispro Insulin Glargine + Insulin Lispro
    Arm/Group Description Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks. Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
    Measure Participants 470 450
    Least Squares Mean (Standard Error) [mg/dL]
    -11.95
    (2.34)
    -15.16
    (2.37)
    14. Secondary Outcome
    Title HbA1c at 26 Weeks
    Description HbA1c is a test that measures a participant's average blood glucose level over the past 2 to 3 months. LS means were calculated using MMRM adjusting for stratification factors (country, LDL-C [<100 mg/dL and ≥100 mg/dL], and number of insulin injections at baseline [1, 2, or ≥3]), treatment, visit, treatment, visit-by-treatment interaction, and baseline HbA1c.
    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 Insulin Glargine + Insulin Lispro
    Arm/Group Description Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks. Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
    Measure Participants 684 672
    Least Squares Mean (Standard Error) [percentage of HbA1c]
    6.76
    (0.04)
    6.97
    (0.04)
    15. Secondary Outcome
    Title Lipid Profile at 26 Weeks
    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], number of insulin injections at baseline [1, 2, or ≥3]), visit, treatment, visit-by-treatment interaction, and baseline value of corresponding lipid outcome variable.
    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 lipid data at both baseline and post-baseline.
    Arm/Group Title LY2605541 + Insulin Lispro Insulin Glargine + Insulin Lispro
    Arm/Group Description Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks. Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
    Measure Participants 684 674
    Cholesterol
    177.17
    (1.13)
    174.79
    (1.14)
    HDL-C
    46.44
    (0.27)
    47.71
    (0.27)
    LDL-C
    97.87
    (0.99)
    98.89
    (0.99)
    Triglycerides
    168.79
    (2.85)
    141.78
    (2.86)
    16. Secondary Outcome
    Title Number of Participants With Change in Anti-LY2605541 Antibodies From Baseline to 26 Weeks
    Description The number 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

    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.
    Arm/Group Title LY2605541 + Insulin Lispro Insulin Glargine + Insulin Lispro
    Arm/Group Description Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks. Participant-specific dose of Insulin Glargine were administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro were administered SC for preprandial and supplemental doses for 26 weeks.
    Measure Participants 682 672
    Number [participants]
    152
    22%
    161
    23.7%
    17. Secondary Outcome
    Title Insulin Treatment Satisfaction Questionnaire (ITSQ) at 26 Weeks
    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, 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 factors (baseline HbA1c [≤8.5% and >8.5%], country, and baseline number of insulin injections [1, 2, or ≥3]) as fixed effects and baseline value of the ITSQ scores as a covariate.
    Time Frame up to 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 Insulin Glargine + Insulin Lispro
    Arm/Group Description Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks. Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
    Measure Participants 631 637
    Least Squares Mean (Standard Error) [units on a scale]
    77.01
    (0.55)
    77.29
    (0.54)
    18. Secondary Outcome
    Title Low Blood Sugar Survey (LBSS) at 26 Weeks
    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 including stratification factors (baseline HbA1c [≤8.5% and >8.5%], country, baseline number of insulin injections [1, 2, or ≥3]), visit, treatment, visit-by-treatment interaction, and baseline LBSS score.
    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 LBSS data at both baseline and post-baseline.
    Arm/Group Title LY2605541 + Insulin Lispro Insulin Glargine + Insulin Lispro
    Arm/Group Description Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks. Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
    Measure Participants 682 671
    Least Squares Mean (Standard Error) [units on a scale]
    21.44
    (0.56)
    21.67
    (0.56)
    19. Secondary Outcome
    Title EuroQoL-5D (EQ-5D) at 26 Weeks
    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 three 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, stratification factors (baseline HbA1c [≤8.5% and >8.5%], country, and baseline number of insulin injections [1, 2, or ≥ 3]), and baseline EQ-5D score.
    Time Frame up to 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 Insulin Glargine + Insulin Lispro
    Arm/Group Description Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks. Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
    Measure Participants 636 644
    Least Squares Mean (Standard Error) [units on a scale]
    0.86
    (0.00)
    0.85
    (0.00)
    20. Secondary Outcome
    Title Rapid Assessment of Physical Activity (RAPA) at 26 Weeks
    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 activity, either strength or flexibility activity (not both), both strength and flexibility 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, multiplied by 100.
    Time Frame up to 26 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 Insulin Glargine + Insulin Lispro
    Arm/Group Description Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks. Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 26 weeks. Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
    Measure Participants 331 346
    RAPA 1, Sedentary
    2.2
    0.3%
    2.4
    0.4%
    RAPA 1, Underactive
    4.6
    0.7%
    6.2
    0.9%
    RAPA 1, Light activity
    21.9
    3.2%
    18.0
    2.7%
    RAPA 1, Regular underactive
    32.7
    4.7%
    27.1
    4%
    RAPA 1, Active
    38.6
    5.6%
    46.3
    6.8%
    RAPA 2, Neither strength/flexibility
    58.3
    8.4%
    53.8
    7.9%
    RAPA 2, Either strength/flexibility
    28.1
    4.1%
    30.6
    4.5%
    RAPA 2, Both strength/flexibility
    13.6
    2%
    15.6
    2.3%

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title LY2605541 + Insulin Lispro Insulin Glargine + Insulin Lispro
    Arm/Group Description Participant-specific doses of LY2605541 were administered SC once daily at bedtime for 26 weeks. Participant-specific doses of Insulin Lispro were administered SC for preprandial and supplemental doses for 26 weeks. Participant-specific doses of Insulin Glargine were administered SC once daily at bedtime for 26 weeks. Participant-specific doses of Insulin Lispro were administered SC for preprandial and supplemental doses for 26 weeks.
    All Cause Mortality
    LY2605541 + Insulin Lispro Insulin Glargine + Insulin Lispro
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    LY2605541 + Insulin Lispro Insulin Glargine + Insulin Lispro
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 79/691 (11.4%) 63/677 (9.3%)
    Blood and lymphatic system disorders
    Anaemia 1/691 (0.1%) 1 1/677 (0.1%) 1
    Cardiac disorders
    Acute myocardial infarction 1/691 (0.1%) 1 1/677 (0.1%) 1
    Angina pectoris 1/691 (0.1%) 1 2/677 (0.3%) 2
    Angina unstable 1/691 (0.1%) 1 1/677 (0.1%) 1
    Atrial fibrillation 2/691 (0.3%) 2 1/677 (0.1%) 2
    Cardiac arrest 0/691 (0%) 0 1/677 (0.1%) 1
    Cardiac failure 1/691 (0.1%) 1 0/677 (0%) 0
    Cardiac failure acute 1/691 (0.1%) 1 0/677 (0%) 0
    Cardio-respiratory arrest 1/691 (0.1%) 1 0/677 (0%) 0
    Coronary artery disease 3/691 (0.4%) 4 2/677 (0.3%) 2
    Coronary artery stenosis 3/691 (0.4%) 3 0/677 (0%) 0
    Hypertensive heart disease 1/691 (0.1%) 1 0/677 (0%) 0
    Myocardial infarction 2/691 (0.3%) 2 1/677 (0.1%) 1
    Nodal arrhythmia 1/691 (0.1%) 1 0/677 (0%) 0
    Ventricular tachycardia 0/691 (0%) 0 1/677 (0.1%) 1
    Ear and labyrinth disorders
    Inner ear disorder 1/691 (0.1%) 2 0/677 (0%) 0
    Vertigo 1/691 (0.1%) 1 0/677 (0%) 0
    Endocrine disorders
    Hyperparathyroidism primary 0/691 (0%) 0 1/677 (0.1%) 1
    Eye disorders
    Cataract 0/691 (0%) 0 1/677 (0.1%) 1
    Panophthalmitis 0/691 (0%) 0 1/677 (0.1%) 1
    Gastrointestinal disorders
    Abdominal pain 0/691 (0%) 0 2/677 (0.3%) 2
    Anal fistula 0/691 (0%) 0 1/677 (0.1%) 1
    Bezoar 0/691 (0%) 0 1/677 (0.1%) 1
    Crohn's disease 1/691 (0.1%) 2 0/677 (0%) 0
    Diarrhoea 1/691 (0.1%) 3 0/677 (0%) 0
    Haematochezia 0/691 (0%) 0 1/677 (0.1%) 1
    Inguinal hernia 1/691 (0.1%) 1 0/677 (0%) 0
    Large intestine polyp 0/691 (0%) 0 1/677 (0.1%) 1
    Oesophagitis 1/691 (0.1%) 3 0/677 (0%) 0
    Pancreatitis 0/691 (0%) 0 1/677 (0.1%) 2
    Small intestinal obstruction 0/691 (0%) 0 1/677 (0.1%) 1
    Umbilical hernia 0/691 (0%) 0 1/677 (0.1%) 1
    General disorders
    Chest pain 1/691 (0.1%) 1 0/677 (0%) 0
    Death 1/691 (0.1%) 1 1/677 (0.1%) 1
    Medical device complication 0/691 (0%) 0 1/677 (0.1%) 1
    Non-cardiac chest pain 2/691 (0.3%) 2 0/677 (0%) 0
    Hepatobiliary disorders
    Cholecystitis acute 0/691 (0%) 0 1/677 (0.1%) 1
    Cholelithiasis 1/691 (0.1%) 1 0/677 (0%) 0
    Drug-induced liver injury 1/691 (0.1%) 1 0/677 (0%) 0
    Hepatic cirrhosis 0/691 (0%) 0 1/677 (0.1%) 2
    Immune system disorders
    Anaphylactic shock 1/691 (0.1%) 1 0/677 (0%) 0
    Drug hypersensitivity 1/691 (0.1%) 1 0/677 (0%) 0
    Hypersensitivity 0/691 (0%) 0 2/677 (0.3%) 2
    Sarcoidosis 0/691 (0%) 0 1/677 (0.1%) 1
    Infections and infestations
    Appendicitis 2/691 (0.3%) 2 0/677 (0%) 0
    Bronchitis 2/691 (0.3%) 2 1/677 (0.1%) 2
    Cellulitis 3/691 (0.4%) 6 1/677 (0.1%) 1
    Diabetic foot infection 1/691 (0.1%) 1 1/677 (0.1%) 1
    Enterococcal infection 0/691 (0%) 0 1/677 (0.1%) 1
    Incision site infection 1/691 (0.1%) 1 0/677 (0%) 0
    Infected skin ulcer 1/691 (0.1%) 1 0/677 (0%) 0
    Infectious mononucleosis 1/691 (0.1%) 1 0/677 (0%) 0
    Osteomyelitis 1/691 (0.1%) 1 0/677 (0%) 0
    Pneumonia 3/691 (0.4%) 3 3/677 (0.4%) 3
    Rotavirus infection 0/691 (0%) 0 1/677 (0.1%) 1
    Subcutaneous abscess 1/691 (0.1%) 1 0/677 (0%) 0
    Viral infection 1/691 (0.1%) 1 0/677 (0%) 0
    Wound infection 1/691 (0.1%) 1 0/677 (0%) 0
    Injury, poisoning and procedural complications
    Acetabulum fracture 1/691 (0.1%) 1 0/677 (0%) 0
    Bone contusion 1/691 (0.1%) 1 0/677 (0%) 0
    Contusion 1/691 (0.1%) 2 1/677 (0.1%) 1
    Coronary artery restenosis 1/691 (0.1%) 1 0/677 (0%) 0
    Excoriation 1/691 (0.1%) 1 0/677 (0%) 0
    Fall 1/691 (0.1%) 1 2/677 (0.3%) 2
    Femur fracture 0/691 (0%) 0 1/677 (0.1%) 1
    Head injury 1/691 (0.1%) 1 0/677 (0%) 0
    Injury 1/691 (0.1%) 1 0/677 (0%) 0
    Lower limb fracture 0/691 (0%) 0 1/677 (0.1%) 1
    Medication error 1/691 (0.1%) 1 0/677 (0%) 0
    Road traffic accident 2/691 (0.3%) 2 2/677 (0.3%) 2
    Skull fractured base 0/691 (0%) 0 1/677 (0.1%) 1
    Subdural haematoma 0/691 (0%) 0 2/677 (0.3%) 3
    Tibia fracture 1/691 (0.1%) 1 0/677 (0%) 0
    Traumatic haematoma 1/691 (0.1%) 2 0/677 (0%) 0
    Upper limb fracture 1/691 (0.1%) 1 1/677 (0.1%) 1
    Investigations
    Catheterisation cardiac 1/691 (0.1%) 1 0/677 (0%) 0
    Metabolism and nutrition disorders
    Fluid overload 1/691 (0.1%) 1 0/677 (0%) 0
    Hypoglycaemia 18/691 (2.6%) 21 12/677 (1.8%) 15
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/691 (0.1%) 2 0/677 (0%) 0
    Bursitis 1/691 (0.1%) 1 0/677 (0%) 0
    Exostosis 1/691 (0.1%) 1 0/677 (0%) 0
    Intervertebral disc protrusion 1/691 (0.1%) 1 1/677 (0.1%) 1
    Mobility decreased 1/691 (0.1%) 1 0/677 (0%) 0
    Musculoskeletal chest pain 1/691 (0.1%) 1 0/677 (0%) 0
    Myalgia 1/691 (0.1%) 1 0/677 (0%) 0
    Osteoarthritis 1/691 (0.1%) 1 0/677 (0%) 0
    Rhabdomyolysis 1/691 (0.1%) 1 0/677 (0%) 0
    Rotator cuff syndrome 1/691 (0.1%) 2 0/677 (0%) 0
    Spinal column stenosis 0/691 (0%) 0 2/677 (0.3%) 5
    Spinal disorder 1/691 (0.1%) 1 0/677 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma 1/691 (0.1%) 1 0/677 (0%) 0
    Breast cancer 0/691 (0%) 0 2/677 (0.3%) 2
    Large intestine benign neoplasm 0/691 (0%) 0 1/677 (0.1%) 1
    Ovarian cancer 1/315 (0.3%) 1 0/273 (0%) 0
    Prostate cancer 1/376 (0.3%) 1 0/404 (0%) 0
    Prostate cancer metastatic 0/376 (0%) 0 1/404 (0.2%) 1
    Rectal adenocarcinoma 0/691 (0%) 0 1/677 (0.1%) 1
    Nervous system disorders
    Carotid artery stenosis 1/691 (0.1%) 1 0/677 (0%) 0
    Cerebrovascular accident 0/691 (0%) 0 1/677 (0.1%) 1
    Diabetic hyperosmolar coma 0/691 (0%) 0 1/677 (0.1%) 1
    Hypoglycaemic unconsciousness 1/691 (0.1%) 1 0/677 (0%) 0
    Ischaemic stroke 2/691 (0.3%) 2 0/677 (0%) 0
    Transient ischaemic attack 3/691 (0.4%) 3 1/677 (0.1%) 1
    Psychiatric disorders
    Adjustment disorder 0/691 (0%) 0 1/677 (0.1%) 1
    Depression 2/691 (0.3%) 4 0/677 (0%) 0
    Panic attack 1/691 (0.1%) 1 0/677 (0%) 0
    Renal and urinary disorders
    Calculus ureteric 1/691 (0.1%) 1 0/677 (0%) 0
    Nephrolithiasis 1/691 (0.1%) 1 1/677 (0.1%) 1
    Renal failure acute 0/691 (0%) 0 2/677 (0.3%) 2
    Renal failure chronic 1/691 (0.1%) 1 0/677 (0%) 0
    Urinary tract obstruction 1/691 (0.1%) 1 0/677 (0%) 0
    Reproductive system and breast disorders
    Postmenopausal haemorrhage 0/315 (0%) 0 1/273 (0.4%) 1
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 0/691 (0%) 0 1/677 (0.1%) 1
    Dyspnoea exertional 1/691 (0.1%) 1 0/677 (0%) 0
    Pleural effusion 0/691 (0%) 0 1/677 (0.1%) 1
    Pulmonary congestion 0/691 (0%) 0 1/677 (0.1%) 2
    Pulmonary oedema 0/691 (0%) 0 1/677 (0.1%) 1
    Respiratory distress 1/691 (0.1%) 1 0/677 (0%) 0
    Skin and subcutaneous tissue disorders
    Blister 1/691 (0.1%) 2 0/677 (0%) 0
    Surgical and medical procedures
    Coronary arterial stent insertion 1/691 (0.1%) 1 1/677 (0.1%) 1
    Knee arthroplasty 1/691 (0.1%) 1 0/677 (0%) 0
    Vascular disorders
    Deep vein thrombosis 1/691 (0.1%) 1 0/677 (0%) 0
    Hypertensive crisis 1/691 (0.1%) 1 0/677 (0%) 0
    Intermittent claudication 0/691 (0%) 0 1/677 (0.1%) 1
    Peripheral arterial occlusive disease 1/691 (0.1%) 1 0/677 (0%) 0
    Subclavian artery stenosis 1/691 (0.1%) 1 0/677 (0%) 0
    Venous insufficiency 0/691 (0%) 0 1/677 (0.1%) 1
    Other (Not Including Serious) Adverse Events
    LY2605541 + Insulin Lispro Insulin Glargine + Insulin Lispro
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 408/691 (59%) 406/677 (60%)
    Eye disorders
    Diabetic retinopathy 7/691 (1%) 8 5/677 (0.7%) 5
    Gastrointestinal disorders
    Abdominal pain 7/691 (1%) 7 4/677 (0.6%) 4
    Constipation 9/691 (1.3%) 9 6/677 (0.9%) 6
    Diarrhoea 24/691 (3.5%) 27 19/677 (2.8%) 22
    Gastrooesophageal reflux disease 7/691 (1%) 7 4/677 (0.6%) 4
    Nausea 16/691 (2.3%) 16 9/677 (1.3%) 10
    Vomiting 11/691 (1.6%) 11 10/677 (1.5%) 13
    General disorders
    Asthenia 0/691 (0%) 0 7/677 (1%) 7
    Fatigue 6/691 (0.9%) 8 16/677 (2.4%) 16
    Oedema peripheral 11/691 (1.6%) 11 26/677 (3.8%) 31
    Pyrexia 8/691 (1.2%) 8 7/677 (1%) 7
    Infections and infestations
    Bronchitis 20/691 (2.9%) 21 20/677 (3%) 22
    Gastroenteritis 8/691 (1.2%) 9 16/677 (2.4%) 16
    Gastroenteritis viral 12/691 (1.7%) 12 6/677 (0.9%) 6
    Influenza 18/691 (2.6%) 19 16/677 (2.4%) 17
    Nasopharyngitis 49/691 (7.1%) 58 63/677 (9.3%) 69
    Pharyngitis 3/691 (0.4%) 3 7/677 (1%) 7
    Sinusitis 16/691 (2.3%) 19 12/677 (1.8%) 13
    Upper respiratory tract infection 29/691 (4.2%) 33 32/677 (4.7%) 39
    Urinary tract infection 18/691 (2.6%) 19 23/677 (3.4%) 26
    Injury, poisoning and procedural complications
    Contusion 4/691 (0.6%) 6 8/677 (1.2%) 9
    Muscle strain 3/691 (0.4%) 3 7/677 (1%) 9
    Investigations
    Alanine aminotransferase increased 11/691 (1.6%) 12 2/677 (0.3%) 3
    Aspartate aminotransferase increased 7/691 (1%) 7 1/677 (0.1%) 1
    Blood creatine phosphokinase increased 2/691 (0.3%) 2 9/677 (1.3%) 9
    Weight increased 5/691 (0.7%) 5 8/677 (1.2%) 8
    Musculoskeletal and connective tissue disorders
    Arthralgia 15/691 (2.2%) 17 15/677 (2.2%) 20
    Back pain 22/691 (3.2%) 25 23/677 (3.4%) 25
    Musculoskeletal pain 6/691 (0.9%) 7 8/677 (1.2%) 10
    Pain in extremity 10/691 (1.4%) 10 14/677 (2.1%) 14
    Nervous system disorders
    Carpal tunnel syndrome 10/691 (1.4%) 11 1/677 (0.1%) 1
    Dizziness 9/691 (1.3%) 11 10/677 (1.5%) 10
    Headache 12/691 (1.7%) 12 19/677 (2.8%) 20
    Hypoaesthesia 7/691 (1%) 8 7/677 (1%) 9
    Psychiatric disorders
    Depression 4/691 (0.6%) 4 7/677 (1%) 7
    Respiratory, thoracic and mediastinal disorders
    Cough 11/691 (1.6%) 11 12/677 (1.8%) 12
    Dyspnoea 5/691 (0.7%) 5 7/677 (1%) 7
    Skin and subcutaneous tissue disorders
    Lipohypertrophy 9/691 (1.3%) 11 0/677 (0%) 0
    Pruritus 7/691 (1%) 7 1/677 (0.1%) 1
    Rash 9/691 (1.3%) 9 7/677 (1%) 8
    Vascular disorders
    Hypertension 14/691 (2%) 16 12/677 (1.8%) 12

    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.

    Results Point of Contact

    Name/Title Chief Medical Officer
    Organization Eli Lilly and Company
    Phone 800-545-5979
    Email
    Responsible Party:
    Eli Lilly and Company
    ClinicalTrials.gov Identifier:
    NCT01468987
    Other Study ID Numbers:
    • 12145
    • I2R-MC-BIAM
    • 2011-001254-29
    First Posted:
    Nov 10, 2011
    Last Update Posted:
    Apr 17, 2018
    Last Verified:
    Mar 1, 2018