A Study in Participants With Type I 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 (country, baseline low density lipoprotein cholesterol \[LDL-C\] \[\<100 milligrams/deciliter (mg/dL) (2.6 millimoles/liter \[mmol/L\]) and ≥100 mg/dL (2.6 mmol/L)\], baseline prior basal insulin therapy \[insulin glargine/detemir/other\]), visit, treatment-by-visit interaction, and baseline HbA1c as the fixed effects and participant as the random effect.

Time frame: 52 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 excursions within a single SMBG profile are included). LS means were calculated using MMRM adjusting for treatment, stratification factors (baseline HbA1c \[≤8.5% and \>8.5%\], country, baseline LDL-C \[\<100 mg/dL (2.6 mmol/L) and ≥100 mg/dL (2.6 mmol/L)\], baseline prior basal insulin therapy \[insulin glargine/detemir/other\]), visit, treatment-by-visit interaction, and baseline excursion as the fixed effects and participant as the random effect.

Time frame: 26 weeks and 52 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, and 52. 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 treatment, stratification factors (baseline HbA1c \[≤8.5% and \>8.5%\], country, baseline LDL-C \[\<100 mg/dL (2.6 mmol/L) and ≥100 mg/dL (2.6 mmol/L)\], baseline prior basal insulin therapy \[insulin glargine/detemir/other\]), visit, treatment-by-visit interaction, and baseline BG values as the fixed effects and participant as the random effect.

Time frame: 26 weeks and 52 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.

Low Blood Sugar Survey (LBSS) (also referenced as Hypoglycemia Fear Survey - II \[HFS-II\]) is a 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-type 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, baseline HbA1c (≤8.5% and \>8.5%), country, baseline prior basal insulin therapy (insulin glargine/detemir/other), visit, treatment-by-visit interaction, and baseline LBSS score as the fixed effects and participant as the random effect.

Time frame: 26 weeks and 52 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.

Basal insulin dose, meal-time insulin dose (short-acting bolus dose), 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 postbaseline visit and stratification variables (baseline HbA1c \[≤8.5% and\> 8.5%\], country, baseline LDL-C \[\<100 mg/dL (2.6 mmol/L) and ≥100 mg/dL (2.6 mmol/L)\], and baseline prior basal insulin therapy \[insulin glargine/detemir/ other\]) as fixed effects.

Time frame: 26 weeks and 52 weeks

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

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 (country, baseline LDL-C \[\<100 mg/dL (2.6 mmol/L) and ≥100 mg/dL (2.6 mmol/L)\], baseline prior basal insulin therapy \[insulin glargine/detemir/other\]), visit, treatment-by-visit interaction, and baseline HbA1c as the fixed effects and participant as the random effect.

Time frame: Baseline, 52 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.

LS means were calculated using MMRM adjusting for treatment, stratification factors (baseline HbA1c \[≤8.5% and \>8.5%\], country, baseline LDL-C \[\<100 mg/dL (2.6 mmol/L) and ≥100 mg/dL (2.6 mmol/L)\], baseline prior basal insulin therapy \[insulin glargine/detemir/other\]), visit, treatment-by-visit interaction, and baseline body weight as fixed effects and participant as the random effect.

Time frame: Baseline, 26 weeks, 52 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.

The EQ-5D-3L 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 an ANCOVA adjusting for treatment, baseline HbA1c (≤8.5% and \>8.5%), country, baseline prior basal insulin therapy (insulin glargine/detemir/other), and baseline EQ-5D-3L score as covariates.

Time frame: up to 52 weeks

Population: Participants who were randomized, had at least 1 dose of study medication, and had evaluable EQ-5D-3L data at both baseline and post-baseline. Missing endpoints were imputed with the LOCF method.

Fasting blood glucose (FBG) was measured by SMBG pre-morning meal. LS means were calculated using MMRM adjusting for treatment, stratification factors (baseline HbA1c \[≤8.5% and \>8.5%\], country, baseline LDL-C \[\<100 mg/dL (2.6 mmol/L) and ≥100 mg/dL (2.6 mmol/L)\], baseline prior basal insulin therapy \[insulin glargine/detemir/other\]), visit, treatment-by-visit interaction, and baseline FBG as the fixed effects and participant as the random effect.

Time frame: 26 weeks and 52 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.

Fasting serum glucose (FSG) is measured in blood before the morning meal. LS means were calculated using MMRM adjusting for treatment, stratification factors (baseline HbA1c \[≤8.5% and \>8.5%\], country, baseline LDL-C \[\<100 mg/dL (2.6 mmol/L) and ≥100 mg/dL (2.6 mmol/L)\], baseline prior basal insulin therapy \[insulin glargine/detemir/other\]), visit, treatment-by-visit interaction, and baseline HbA1c as the fixed effects and participant as the random effect.

Time frame: 26 weeks and 52 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 the past 2 to 3 months. LS means were calculated using MMRM adjusting for treatment, stratification factors (country, baseline LDL-C \[\<100 mg/dL (2.6 mmol/L) and ≥100 mg/dL (2.6 mmol/L)\], baseline prior basal insulin therapy \[insulin glargine/detemir/other\]), 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.

Insulin Treatment Satisfaction Questionnaire (ITSQ) is a validated measure containing 22 items that assess treatment satisfaction for participants with diabetes and on insulin. The questionnaire measures satisfaction from the following 5 domains: Convenience of Regimen, Lifestyle Flexibility, Glycemic Control, Hypoglycemic Control, and Insulin Delivery Device. Data are transformed to a scale of 0-100, where higher scores indicate better treatment satisfaction. LS means were calculated using an ANCOVA model adjusting for treatment, baseline HbA1c (≤8.5% and \>8.5%), country, and baseline prior basal insulin therapy (insulin glargine/detemir/other) as fixed effects and baseline ITSQ scores as a covariate.

Time frame: up to 52 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.

FBG was measured by SMBG. Between-day glucose variability is measured by the standard deviation (SD) of FBG. LS means were calculated using MMRM adjusting for treatment, stratification factors (baseline HbA1c \[≤8.5% and \>8.5%\], country, baseline LDL-C \[\<100 mg/dL (2.6 mmol/L) and ≥100 mg/dL (2.6 mmol/L)\], baseline prior basal insulin therapy \[insulin glargine/detemir/other\]), visit, treatment-by-visit interaction, and baseline SD of FBG as the fixed effects and participant as the random effect.

Time frame: 26 weeks and 52 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.

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, Baseline through 52 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 anti-LY2605541 treatment-emergent 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: 26 weeks, 52 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.

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, up to 52 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 last observation carried forward (LOCF) method, using only post-baseline data.

Hypoglycemic episodes are defined as events 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, up to 52 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, using only post-baseline data.

Hypoglycemic episodes are defined as events associated with the 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, Baseline through 52 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 events that are associated with the 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, Baseline through 52 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 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 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: 52 weeks

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

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 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, Baseline through 52 weeks

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

Concentrations of cholesterol, HDL-C, and LDL-C, and triglycerides are presented. LS means were calculated using MMRM adjusting for stratification factors (baseline HbA1c \[≤8.5% and \>8.5%\], country, LDL-C \[\<100 mg/dL (2.6 mmol/L) and ≥100 mg/dL (2.6 mmol/L), except for the LDL-C outcome variable\], prior basal insulin therapy \[insulin glargine/detemir/other\]), visit, treatment, treatment-by-visit interaction, and baseline value of corresponding lipid outcome variable as the fixed effects and participant as a random effect.

Time frame: 26 weeks and 52 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.