A Study of LY2605541 in Participants With Type 1 Diabetes Mellitus

HbA1c is a test that measures a person's average blood glucose level over the past 2 to 3 months. Least Squares (LS) means were calculated using a mixed model repeated measures (MMRM) analysis including the following fixed effects: treatment, period, sequence, baseline HbA1c (last nonmissing value at or before randomization), week (defined from the start of each Randomization Period), and treatment-by-week interaction.

Total hypoglycemic events (HE) include any event based on a blood glucose <=70 milligrams per deciliter (mg/dL) (3.9 millimoles per liter [mmol/L]), with or without signs/symptoms of hypoglycemia or an event associated with signs/symptoms of hypoglycemia but without a glucose measurement. Nocturnal HE include any total HE that occurred between bedtime and waking. Group Means are presented and were calculated from negative binomial regression models (number of episodes = treatment + period + treatment sequence + baseline HbA1c [<=8.0% or >8.0%], with log [exposure in days/30] as an offset variable). Group Mean (LS mean) is estimated by taking the inverse link function on individual participant covariates first and then averages over all participants.

Total HE include any event based on a blood glucose <=70 mg/dL (3.9 mmol/L), with or without signs/symptoms of hypoglycemia or an event associated with signs/symptoms of hypoglycemia but without a glucose measurement. Nocturnal HE include any total HE that occurred between bedtime and waking. 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.

FBG was measured by self-monitored blood glucose (SMBG). LS means were calculated using MMRM analysis including the following fixed effects: treatment, period, sequence, baseline FBG (last nonmissing value at or before randomization), baseline HbA1c (<=8.0% or >8.0%), week (defined from the start of each Randomization Period), and treatment-by-week interaction.

FBG was measured by SMBG. Between-day glucose variability is measured by the standard deviation of FBG. LS means were calculated using MMRM analysis including the following fixed effects: treatment, period, sequence, baseline intra-participant variability in FBG (last nonmissing value at or before randomization), baseline HbA1c (<=8.0% or >8.0%), week (defined from the start of each Randomization Period), and treatment-by-week interaction.

LS means for FSG (obtained from clinical laboratory tests) were calculated using MMRM analysis including the following fixed effects: treatment, period, sequence, baseline FSG (last nonmissing value at or before randomization), baseline HbA1c (<=8.0% or >8.0%), week (defined from the start of each Randomization Period), and treatment-by-week interaction.

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. SMBG measures were assessed at Weeks 0, 4, 8, and 12 within each Randomization Period. LS means were calculated using MMRM analysis including the following fixed effects: treatment, period, sequence, baseline SMBG (last nonmissing value at or before randomization), baseline HbA1c (<=8.0% or >8.0%), week (defined from the start of each Randomization Period), and treatment-by-week interaction.

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. SMBG measures were assessed at Weeks 0, 4, 8, and 12 within each Randomization Period. LS means were calculated using MMRM analysis including the following fixed effects: treatment, period, sequence, baseline SMBG (last nonmissing value at or before randomization), baseline HbA1c (<=8.0% or >8.0%), week (defined from the start of each Randomization Period), and treatment-by-week interaction.

A summary of glucose variability (intra-participant variability) as measured by the average of between-day standard deviations of individual SMBG time points. LS means were calculated using MMRM analysis including the following fixed effects: treatment, period, sequence, baseline intra-participant variability in SMBG (last nonmissing value at or before randomization), baseline HbA1c (<=8.0% or >8.0%), week (defined from the start of each Randomization Period), and treatment-by-week interaction.

LS means were calculated using MMRM analysis including the following fixed effects: treatment, period, sequence, baseline body weight (last nonmissing value at or before randomization), baseline HbA1c (<=8.0% or >8.0%), week (defined from the start of each Randomization Period), and treatment-by-week interaction.

LS means were calculated using MMRM analysis, including visit and baseline weight (last non-missing value at or before the beginning of Lead-in Period) as covariates.

LS means were calculated using MMRM analysis including the following fixed effects: treatment, period, sequence, baseline HbA1c (last nonmissing value at or before randomization), week (defined from the start of each Randomization Period), and treatment-by-week interaction.

The number of participants with a treatment emergent anti-LY2605541 antibody response (TEAR) is presented. Positive TEAR was defined as change from baseline to post-baseline in the anti-LY2605541 antibody level either from 1) undetectable to detectable or from 2) detectable to the value with at least 130% relative increase from baseline.

LS means were calculated using MMRM analysis including the following fixed effects: treatment, period, sequence, baseline insulin dose (last nonmissing value at or before randomization), baseline HbA1c (<=8.0% or >8.0%), week (defined from the start of each Randomization Period), and treatment-by-week interaction.

Proportion of bolus to total insulin dose is presented, where LS means were calculated using MMRM analysis including the following fixed effects: treatment, period, sequence, baseline proportion of bolus to total insulin dose (last nonmissing value at or before randomization), baseline HbA1c (<=8.0% or >8.0%), week (defined from the start of each Randomization Period), and treatment-by-week interaction.

Excursion results were calculated by subtracting the 0300 hours glucose value from the next day pre-morning glucose value within a single SMBG profile. LS means were calculated using MMRM analysis including the following fixed effects: treatment, period, sequence, baseline 0300-hour to next day pre-breakfast excursion (last nonmissing value at or before randomization), baseline HbA1c (<=8.0% or >8.0%), week (defined from the start of each Randomization Period), and treatment-by-week interaction.

LS means were calculated using MMRM analysis including visit and baseline lipid level (last nonmissing value at or before the beginning of Lead-in) as covariates.

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.