A Study in Participants With Type 1 Diabetes Mellitus

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

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

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

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

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

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

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

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

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

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

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

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

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

Population: 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.

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

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

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

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

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

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

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

Population: 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.

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

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

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

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

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

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

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

Population: 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.

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

Population: 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.

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

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

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

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

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

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

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

Population: 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.

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

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