A Study in Patients With Type 2 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) with baseline HbA1c measurement, stratification factors (country, low density lipoprotein-cholesterol \[LDL-C, \< 100 milligrams per deciliter {mg/dL} and ≥ 100 mg/dL\] and sulfonylurea \[SU\]/meglitinide use), visit, treatment, and visit-by-treatment interaction as fixed effects.

Time frame: Baseline, 52 weeks

Population: All participants who were randomized, had at least 1 dose of study medication, and at least 1 post-baseline HbA1c measurement.

Six-point SMBG profiles were obtained at pre-morning meal (fasting), pre-midday meal (lunch), pre-evening meal (dinner), bedtime, approximately 0300 hours, and pre-morning meal (fasting) the next day. Six-point SMBG profiles were obtained over 2 nonconsecutive days within the week prior to the next office visit. LS means were calculated using a MMRM with baseline blood glucose measurement, stratification factors (country, HbA1c, LDL-C \[\< 100 mg/dL and ≥ 100 mg/dL\], and SU/meglitinide use), treatment, visit, and treatment-by-visit interaction as fixed effects.

Time frame: 52 weeks

Population: All participants who were randomized, received at least 1 dose of study drug, and had evaluable SMBG data.

The adult Low Blood Sugar Survey (LBSS) is a validated, participant-reported 33-item questionnaire with items rated on a 5-point Likert scale, where 0 = never and 4 = always. The LBSS measures behaviors to avoid hypoglycemia and its negative consequences (15 items) and worries about hypoglycemia and its negative consequences (18 items). Total score is the sum of all items (range of 0 to 132). Higher total scores reflect greater fear of hypoglycemia. LS means were calculated using an analysis of covariance model (ANCOVA) with baseline LBSS score, stratification factors (country, HbA1c, and SU/meglitinide use), and treatment as fixed effects.

Time frame: Up to 52 weeks

Population: All participants who were randomized, received at least 1 dose of study drug, and had evaluable LBSS data. Missing endpoints were imputed with the last observation carried forward (LOCF) method, using only post-baseline data.

LS means were calculated using a MMRM with baseline body weight measurement, stratification factors (country, HbA1c, LDL-C \[\< 100 mg/dL and ≥ 100 mg/dL\], and SU/meglitinide use), treatment, visit, and treatment-by-visit interaction as fixed effects.

Time frame: Baseline, 52 weeks

Population: All participants who were randomized, who received at least 1 dose of study drug, and had evaluable body weight data.

LS means were calculated using a MMRM with baseline lipid measurement, stratification factors (country, HbA1c, LDL-C \[\< 100 mg/dL and ≥ 100 mg/dL\], and SU/meglitinide use), treatment, visit, and treatment-by-visit interaction as fixed effects.

Time frame: Baseline, 52 weeks

Population: All participants who were randomized, received at least 1 dose of study drug, and had at least 1 post-baseline lipid measurement.

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 to 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 a MMRM with baseline stratification factors (country, HbA1c, and SU/meglitinide use), treatment, visit, and treatment-by-visit interaction as fixed effects.

Time frame: 52 weeks

Population: All participants who were randomized, received at least 1 dose of study drug, and had evaluable EQ-5D data.

LS means were calculated using a MMRM with baseline fasting blood glucose measurement, stratification factors (country, HbA1c, LDL-C \[\< 100 mg/dL and ≥ 100 mg/dL\], and SU/meglitinide use), treatment, visit, and treatment-by-visit interaction as fixed effects.

Time frame: 52 weeks

Population: All participants who were randomized, received at least 1 dose of study drug, and had evaluable fasting blood glucose data.

LS means were calculated using a MMRM with baseline fasting serum glucose measurement, stratification factors (country, HbA1c, LDL-C \[\< 100 mg/dL and ≥ 100 mg/dL\], and SU/meglitinide use), treatment, visit, and treatment-by-visit interaction as fixed effects.

Time frame: 52 weeks

Population: All participants who were randomized, received at least 1 dose of study drug, and had evaluable fasting serum glucose data.

HbA1c is a test that measures a person's average blood glucose level over the past 2 to 3 months. LS means were calculated using a MMRM with baseline HbA1C measurement, stratification factors (country, HbA1c, LDL-C \[\< 100 mg/dL and ≥ 100 mg/dL\], and SU/meglitinide use), treatment, visit, and treatment-by-visit interaction as fixed effects.

Time frame: 52 weeks

Population: All participants who were randomized, received at least 1 dose of study drug, and had at least 1 post-baseline HbA1c measurement.

LS means were calculated using a MMRM with baseline insulin dose measurement, stratification factors (country, HbA1c, LDL-C \[\< 100 mg/dL and ≥ 100 mg/dL\], and SU/meglitinide use), treatment, visit, and treatment-by-visit interaction as fixed effects.

Time frame: 52 weeks

Population: All participants who were randomized, received at least 1 dose of study drug, and had evaluable insulin dose data.

The Insulin Treatment Satisfaction Questionnaire (ITSQ) is a validated instrument containing 22 items that assess treatment satisfaction for participants with diabetes who are receiving 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 total score on a scale of 0 to 100, where higher scores indicate better treatment satisfaction. LS means were calculated using a MMRM with stratification factors (country, HbA1c, and SU/meglitinide use), treatment, visit, and treatment-by-visit interaction as fixed effects.

Time frame: Up to 52 weeks

Population: All participants who were randomized, received at least 1 dose of study drug, and had evaluable ITSQ data.

Intra-participant variability of FBG, which was measured by SMBG, was assessed by the standard deviation of the FBG measurement at the Week 52 visit. LS means were calculated using a MMRM with baseline fasting blood glucose measurement, stratification factors (country, HbA1c, LDL-C \[\< 100 mg/dL and ≥ 100 mg/dL\], and SU/meglitinide use), treatment, visit, and treatment-by-visit interaction as fixed effects.

Time frame: 52 weeks

Population: All participants who were randomized, received at least 1 dose of study drug, and had evaluable post-baseline FBG data.

Insulin doses were adjusted according to an algorithm (adapted from Riddle et al. 2003) during the first 26 weeks of the study and thereafter according to investigator judgment. Steady-state was defined as the first local maximum dose (maximum of moving 4-week interval) of LY2605541 or glargine within the window of +/- 2 weeks. The number of dose adjustments to steady-state was the total number of dose changes until steady-state was reached. LS means were calculated using a MMRM with baseline insulin dose measurement, stratification factors (country, HbA1c, LDL-C \[\< 100 mg/dL and ≥ 100 mg/dL\], and SU/meglitinide use), treatment, visit, and treatment-by-visit interaction as fixed effects.

Time frame: Baseline to 52 weeks

Population: All participants who were randomized, received at least 1 dose of study drug, and had evaluable post-baseline insulin data.

The percentage of participants with a TEAR is summarized. TEAR is defined as a change in the anti-LY2605541 antibody level from undetectable at baseline to detectable at baseline, or, for those participants with detectable antibodies at baseline, change to a value with at least a 130% relative increase from baseline. Overall TEAR is defined as one or more TEAR during the specified period.

Time frame: Baseline to 78 weeks

Population: All participants who were randomized, received at least 1 dose of study drug, and had evaluable TEAR data.

The percentage of participants was calculated by dividing the number of participants equal or above 2- or 3-fold ULN for ALT/SGPT or AST/SGOT by the total number of participants analyzed, multiplied by 100.

Time frame: Up to 52 weeks

Population: All participants who were randomized, received at least 1 dose of study drug, and had evaluable post-baseline liver enzyme data.

Time frame: Up to 52 weeks

Population: All participants who were randomized, had at least 1 dose of study drug, and had at least 1 post-baseline total bilirubin measurement.

The percentage of participants with HbA1C ≤ 6.5% or \< 7.0% without nocturnal hypoglycemia is presented. Percentage was calculated by dividing the number of participants with the indicated HbA1c values over the total number of participants and multiplying by 100.

Time frame: Up to 52 weeks

Population: All participants who were randomized, received at least 1 dose of study drug, and had at least 1 post-baseline HbA1c measurement. Missing endpoints were imputed with the LOCF method, using only 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: 52 weeks

Population: All participants who were randomized, received at least 1 dose of study drug, and had at least 1 post-baseline HbA1c measurement.

A hypoglycemic event is defined by a blood glucose value ≤70 mg/dL (3.9mmol/L). Total hypoglycemic events include documented symptomatic hypoglycemia, asymptomatic hypoglycemia, probable symptomatic hypoglycemia, unspecified hypoglycemia, or severe hypoglycemia. Nocturnal hypoglycemic events refer to any total hypoglycemic event that occurs between bedtime and waking. The percentage of participants was calculated by dividing the number of participants with hypoglycemic or nocturnal hypoglycemic events by the total number of participants analyzed, multiplied by 100.

Time frame: Baseline to 52 weeks

Population: All participants who were randomized, received at least 1 dose of study drug, and had evaluable hypoglycemia event data.

Hypoglycemia is a condition that occurs when a person's blood glucose level is lower than the normal range (less than or equal to 70 milligrams per deciliter \[mg/dL\] or less than 3.9 millimoles per liter \[mmol/L\]). Total hypoglycemia refers to an event that meets the criteria for documented symptomatic hypoglycemia, asymptomatic hypoglycemia, probable symptomatic hypoglycemia, unspecified hypoglycemia, or severe hypoglycemia. Nocturnal hypoglycemia refers to any total hypoglycemic event that occurs between bedtime and waking. Group mean (listed as LS means below) rates of total and nocturnal hypoglycemia were calculated using a negative binomial regression model (number of episodes = treatment + SU/meglitinide use + baseline hypoglycemia event rate, with log \[exposure per 30 days\] as the offset variable in the model).

Time frame: Baseline to 52 weeks

Population: All participants who were randomized, who received at least 1 dose of study drug, and had evaluable total and/or nocturnal event data.