A Study of LY2605541 in Participants With Type 2 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 stratification factors (country, baseline low-density lipoprotein cholesterol \[LDL-C, \<100 milligrams per deciliter (mg/dL) and ≥100 mg/dL\], and sulfonylurea (SU) or meglitinide use), visit, treatment, visit-by-treatment interaction, and baseline HbA1c.

Time frame: Baseline, 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.

SMBG measurements were taken at 6 time points (pre-morning meal \[fasting\], pre-midday meal, pre-evening meal, bedtime, approximately 0300 hours, and pre-morning meal \[fasting\] on the next day) and were performed on 2 non-consecutive days in the week prior to next office visit. 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 SU or meglitinide use), visit, treatment, visit-by-treatment interaction, and baseline BG values.

Time frame: 26 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.

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 ANCOVA with treatment and stratification factors (country, baseline HbA1c \[≤8.5% and \>8.5%\], and SU or meglitinide use) as fixed effects and baseline value of the LBSS score as a covariate.

Time frame: 26 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. Missing endpoints were imputed by applying the LOCF method to the post-baseline data.

LS means were calculated using MMRM adjusting for stratification factors (country, baseline HbA1c \[≤8.5% and \>8.5%\], LDL-C \[\<100 mg/dL and ≥100 mg/dL, except for the LDL-C outcome variable\], and SU or meglitinide use), visit, treatment, visit-by-treatment interaction, and baseline body weight.

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.

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 (country, baseline HbA1c \[≤8.5% and \>8.5%\], LDL-C \[\<100 mg/dL and ≥100 mg/dL, except for the LDL-C outcome variable\], and SU or meglitinide use), visit, treatment, visit-by-treatment interaction, and baseline value of corresponding lipid outcome variable.

Time frame: Baseline, 26 weeks, 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.

LS means were calculated using MMRM adjusting for stratification factors (country, baseline LDL-C \[\<100 mg/dL and ≥100 mg/dL\], and SU or meglitinide use), visit, treatment, visit-by-treatment interaction, and baseline HbA1c.

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.

The EuroQol-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 an analysis of covariance (ANCOVA) model adjusting for treatment, stratification factors (country, baseline HbA1c \[≤8.5% and \>8.5%\], and SU or meglitinide use), and baseline EuroQol-5D score.

Time frame: 26 weeks

Population: Participants who were randomized, had at least 1 dose of study medication, and had evaluable EuroQol-5D data at both baseline and post-baseline. Missing endpoints were imputed by applying the LOCF method to the post-baseline data.

LS means were calculated using MMRM adjusting for stratification factors (country, baseline HbA1c \[≤8.0% and \>8.0%\], baseline LDL-C \[\<100 mg/dL and ≥100 mg/dL\], and SU or meglitinide use), visit, treatment, visit-by-treatment interaction, and baseline FBG.

Time frame: 26 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.

LS means were calculated using MMRM adjusting for stratification factors (country, baseline HbA1c \[≤8.0% and \>8.0%\], baseline LDL-C \[\<100 mg/dL and ≥100 mg/dL\], and SU or meglitinide use), visit, treatment, visit-by-treatment interaction, and baseline FSG.

Time frame: 26 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.

LS means were calculated using MMRM adjusting for stratification factors (country, baseline LDL-C \[\<100 mg/dL and ≥100 mg/dL\], and SU or meglitinide use), visit, treatment, visit-by-treatment interaction, and baseline HbA1c.

Time frame: 26 and 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.

Daily basal insulin dose is presented. LS means were calculated using MMRM adjusting for the stratification factors (country, baseline HbA1c \[≤8.5% and \>8.5%\], baseline LDL-C \[\<100 mg/dL and ≥100 mg/dL\], and SU or meglitinide use), treatment, visit, treatment-by-visit interaction, and baseline insulin dose.

Time frame: 26 and 52 weeks

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

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 a higher score indicate better treatment satisfaction. LS means were calculated using ANCOVA with treatment and stratification factors (country, baseline HbA1c \[≤8.5% and \>8.5%\], and SU or meglitinide use) as fixed effects and baseline value of the ITSQ score 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 by applying the LOCF method to the post-baseline data.

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 (country, baseline HbA1c \[≤8.5% and \>8.5%\], baseline LDL-C \[\<100 mg/dL and ≥100 mg/dL\], and SU or meglitinide use), treatment, visit, treatment-by-visit interaction, and baseline FBG intra-participant variability.

Time frame: 26 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.

The number of dose adjustments required to reach a steady dose is presented. LS means were calculated from negative binomial regression models, where the number of dose adjustments = treatment + stratification factors (country, baseline HbA1c \[≤8.5% and \>8.5%\], baseline LDL-C \[\<100 mg/dL and ≥100 mg/dL\], and SU or meglitinide use).

Time frame: Baseline through 26 weeks

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

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 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.

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). A nocturnal hypoglycemic event 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.

Time frame: Baseline through 26 weeks and 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 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. 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: 26 and 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 by applying the LOCF method to the post-baseline data.

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: 26 and 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 by applying the last observation carried forward (LOCF) method to the post-baseline 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 millimoles per liter \[mmol/L\]). A nocturnal hypoglycemic event occurred between bedtime and waking. Group mean rates of total and nocturnal hypoglycemia (per 30 days) are presented and were calculated from negative binomial regression models (number of episodes = treatment + baseline hypoglycemia rate + baseline SU or meglitinide use, 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

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