A Study in Adults With Type 2 Diabetes

HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by analysis of covariance (ANCOVA) and adjusted for Baseline HbA1c, country, sulfonylurea use, time of basal insulin injection and treatment.

Time frame: Baseline, Endpoint (up to 24 weeks)

Population: All randomized participants who received at least 1 dose of study drug and with a Baseline and at least 1 post-Baseline HbA1c measure; last observation carried forward (LOCF).

Seven-point SMBG are completed at the following timepoints: Morning (AM) Pre-Meal, Morning (AM) Post-Prandial (PP), Midday (MD) Pre-Meal, Midday PP, Evening (EV) Pre-Meal, Bed Time and 0300 hours. PP glucose is measured 2 hours (hrs) after the start of the meal. Least Squares (LS) means are determined by analysis of covariance (ANCOVA) and adjusted for Baseline HbA1c, country, sulfonylurea use, time of basal insulin injection, and treatment.

Time frame: Baseline and Endpoint [up to 24 weeks (wk)]

Population: All randomized participants who received at least 1 dose of study drug with Baseline and at least 1 post-Baseline SMBG measure; last observation carried forward (LOCF).

ALBSS contains 33 items, with each item scored on a 5-point response scale: 0 (never) to 4 (almost always). Items are categorized in 2 domains: Behavior (or avoidance) Items 1 to 15 and Worry (or affect) Items 16 to 33. Behavior Total Score range is 0 to 60 and Worry Total Score range is 0 to 72. Higher scores on Behavior items (related to avoidance of hypoglycemia) reflect greater awareness and/or effort of the participant to prevent low blood sugar. Higher scores on Worry items (related to worries about low blood sugar and its consequences) reflect greater participant concern about having low blood sugar. The ALBSS Total Scores (Worry and Behavior item scores combined) range is 0 to 132. Least Squares (LS) means are determined by analysis of covariance (ANCOVA) and adjusted for Baseline HbA1c, country, sulfonylurea use, time of basal insulin injection, and treatment.

Time frame: 4 weeks (wk) and 12 wk and Endpoint (up to 24 wk)

Population: All randomized participants who received at least 1 dose of study drug with Baseline and at least 1 post-Baseline ALBSS measure; last observation carried forward (LOCF).

Change from baseline in body weight. Least Squares (LS) means are determined by analysis of covariance (ANCOVA) and adjusted for Baseline HbA1c, country, sulfonylurea use, time of basal insulin injection, and treatment.

Time frame: Baseline and 4 weeks (wk) and 8 wk and 12 wk and 16 wk and 20 wk and 24 wk and Endpoint (up to 24 wk)

Population: All randomized participants who received at least 1 dose of study drug with Baseline and at least 1 post-Baseline body weight measure; last observation carried forward (LOCF).

HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) means are determined by analysis of covariance (ANCOVA) and adjusted for Baseline HbA1c, country, sulfonylurea use, time of basal insulin injection and treatment.

Time frame: Baseline and 4 weeks and 8 weeks and 12 weeks and 16 weeks and 20 weeks and 24 weeks

Population: All randomized participants who received at least 1 dose of study drug with Baseline and at least 1 post-Baseline HbA1c measure.

Blood samples are collected from participants and percentage of insulin antibody binding measured. Least Squares (LS) means are determined by analysis of covariance (ANCOVA) and adjusted for Baseline of response and treatment.

Time frame: Baseline and 4 weeks and 12 weeks and Endpoint (24 weeks and up to 24 weeks)

Population: All randomized participants who received at least 1 dose of study drug and with a Baseline and at least 1 post-Baseline insulin antibody measure; last observation carried forward (LOCF).

Glycemic variability is measured by the intra-participant standard deviation (SD) value of fasting blood glucose as measured by the actual morning pre-meal blood glucose value from the 7-point self-monitoring blood glucose \[SMBG\] profiles. Least Squares (LS) means are determined by analysis of covariance (ANCOVA) and adjusted for baseline HbA1c, country, sulfonylurea use, time of basal insulin injection, and treatment.

Time frame: Baseline and Endpoint (up to 24 weeks)

Population: All randomized participants who received at least 1 dose of study drug with Baseline and at least 1 post-Baseline fasting blood glucose measure; last observation carried forward (LOCF).

A hypoglycemic event is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia, or has blood glucose (BG) concentration of ≤70 milligrams/deciliter (mg/dL) even if it was not associated with signs, symptoms, or treatment consistent with current American Diabetes Association (ADA: 2005) guidelines. Severe hypoglycemia is defined as a hypoglycemic event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions (these episodes may be associated with sufficient neuroglycopenia to induce seizure or coma; also, BG measurements may not be available during such an event). Nocturnal hypoglycemia is defined as any hypoglycemic event that occurs between bedtime and waking.

Time frame: Baseline and Endpoint (up to 24 weeks)

Population: All randomized participants who received at least 1 dose of study drug with Baseline and at least 1 post-Baseline hypoglycemic event measure.

Insulin dose in units (U) per body weight in kilograms (kg) per day. Least Squares (LS) means are determined by analysis of covariance (ANCOVA) and adjusted for Baseline HbA1c, country, sulfonylurea use, time of basal insulin injection, and treatment.

Time frame: Endpoint (up to 24 weeks)

Population: All randomized participants who received at least 1 dose of study drug with Baseline and at least 1 post-Baseline Insulin Dose per Body Weight measure; last observation carried forward (LOCF).

Units of insulin taken daily. Least Square (LS) means are determined by analysis of covariance (ANCOVA) and adjusted for Baseline HbA1C, country, sulfonylurea use, time of basal insulin injection and treatment.

Time frame: Endpoint (up to 24 weeks)

Population: All randomized participants who received at least 1 dose of study drug with Baseline and at least 1 post-Baseline insulin dose measure; last observation carried forward (LOCF).

ITSQ is a validated instrument containing 22 items that assess treatment satisfaction for participants with diabetes and on insulin. Items divided into 5 domains of satisfaction: Inconvenience of Regimen \[(IR) 5 items: domain scores range (DSR) 5-35\], Lifestyle Flexibility \[(LF) 3 items: DSR 3-21\], Glycemic Control \[(GC) 3 items: DSR 3-21\], Hypoglycemic Control \[(HC) 5 items: DSR 5-35\], Insulin Delivery Device \[(IDD) 6 items: DSR 6-42\]. All items measured on a 7-point scale: 1 (no bother at all) to 7 (a tremendous bother), with lower scores reflecting better outcomes. ITSQ Total Overall Raw Scores range from 22-154. Both raw domain and overall scores are transformed on a scale of 0-100, where transformed score=100\*\[(7-mean raw score)/6\]. Higher scores indicate better treatment satisfaction. Least Squares (LS) mean are determined by analysis of covariance (ANCOVA) and adjusted for Baseline HbA1c, country, sulfonylurea use, time of basal insulin injection, and treatment.

Time frame: 4 weeks (wk) and 12 wk and Endpoint (EP) (up to 24 wk)

Population: All randomized participants who received at least 1 dose of study drug with Baseline and at least 1 post-Baseline ITSQ measure; last observation carried forward (LOCF).

Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time.

Time frame: Baseline and 4 weeks and 8 weeks and 12 weeks and 16 weeks and 20 weeks and 24 weeks and Endpoint (up to 24 weeks)

Population: All randomized participants who received at least 1 dose of study drug with Baseline and at least 1 post-Baseline HbA1c measure; last observation carried forward (LOCF).

The rate of hypoglycemic events per 30 days between two visits is defined as the total number of events between the visits divided by the actual number of days between the visits, and then multiplied by 30 days. A hypoglycemic event is defined as any time a participant has a blood glucose (BG) level of ≤70 milligrams per deciliter (mg/dL) even if the event was not associated with signs, symptoms, or treatment consistent with current guidelines (American Diabetes Association 2005). Nocturnal hypoglycemia is defined as any hypoglycemic event that occurs between bedtime and waking. Severe hypoglycemia is defined as a hypoglycemic event requiring assistance of another person to actively administer carbohydrates, glucagons, or other resuscitative actions. Severe Hypoglycemic events may or may not have a reported BG ≤70 mg/dL. These events may be associated with sufficient neuroglycopenia to induce seizure or coma.

Time frame: Baseline, Endpoint (up to 24 weeks)

Population: All randomized participants who received at 1 dose of study drug with Baseline at least 1 post-Baseline hypoglycemic event.

Time frame: Baseline and 4 weeks and 12 weeks and 24 weeks and Endpoint (up to 24 weeks) and Baseline to 24 weeks (Overall)

Population: All randomized participants who received at least 1 dose of study drug with Baseline and at least 1 post-Baseline analysis to detect insulin antibodies; last observation carried forward (LOCF).

TEAR is defined as an absolute increase of at least 1% in insulin antibody levels (measured in % binding) and at least 30% relative increase from Baseline for participants who are insulin antibody-positive at Baseline, or turning from insulin antibody-negative status at Baseline to antibody-positive during the course of the study following treatment with study drug.

Time frame: 4 weeks and 12 weeks and 24 weeks and Endpoint (up to 24 weeks) and Baseline to 24 weeks (Overall)

Population: All randomized participants who received at least 1 dose of study drug with Baseline and at least 1 post-Baseline analysis to detect insulin antibodies; last observation carried forward (LOCF).