Comparison of the Efficacy and Safety of Two Insulin Intensification Strategies

Eli Lilly and Company478 enrolled

Overview

The study is a comparison of twice-daily insulin lispro low mixture versus once-daily basal insulin glargine and once-daily prandial insulin lispro, in participants with Type 2 Diabetes.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

478

Conditions

Diabetes Mellitus, Type 2

Interventions

Insulin Lispro Low Mixture (LM)DRUG

Participant-dependent dose, administered subcutaneously for 24 weeks

Insulin GlargineDRUG

Participant-dependent dose, administered subcutaneously for 24 weeks

Prandial Insulin LisproDRUG

Participant-dependent dose, administered subcutaneously for 24 weeks

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Present with type 2 diabetes mellitus * Have been taking metformin and/or pioglitazone * Have received treatment with basal insulin glargine, injected once a day, for greater than or equal to 90 days * Have glycosylated hemoglobin A1c (HbA1c) concentration between greater than or equal to 7.5% and less than or equal to 10.5 * Have a fasting plasma glucose concentration of less than or equal to 6.7 millimoles per liter \[mmol/L, less than or equal to 121 milligrams per deciliter (mg/dL)\], or greater than 6.7 mmol/L (greater than 121 mg/dL) if the investigator considers that further titration of basal insulin glargine is not possible for safety reasons * Not pregnant or breastfeeding Exclusion Criteria: * Have Type 1 Diabetes * Their stable dose of pioglitazone is greater than the maximum dose approved for use in combination with insulin in their country * Have a body mass index (BMI) greater than 45 kilograms per square meter (kg/m2). * Have a history of scheduled mealtime (prandial) insulin use within 12 weeks of the screening visit and the total duration of the prandial insulin treatment was greater than 2 weeks * Have had more than one episode of severe hypoglycaemia within 24 weeks prior to entry into the study * Have cardiac disease with a functional status that is Class III or IV * Have a history of renal or liver disease * Have had a blood transfusion or have a blood disorder

Locations (18)

Outcomes

Primary Outcomes

Change in HbA1c From Baseline to 24 Weeks Endpoint (Per Protocol Population)

The change from baseline to 24 weeks in the percentage of glycosylated hemoglobin A1c (HbA1c) in plasma. The least squares (LS) mean was estimated from a mixed-effects model with repeated measures (MMRM) that included baseline HbA1c concentration as a covariate, treatment, country, week of visit, and treatment-by-week interaction as fixed effects, and participant and error as random effects.

Time frame: Baseline, 24 weeks

Change in HbA1c From Baseline to 24 Weeks Endpoint (Intention-to-Treat Population)

Time frame: Baseline, 24 weeks

Secondary Outcomes

Change in the HbA1c Concentration From Baseline to 12 Weeks Endpoint

The change from baseline to 12 weeks in the percentage of glycosylated hemoglobin A1c (HbA1c) in plasma. The least squares (LS) mean was estimated from a mixed-effects model with repeated measures (MMRM) that included baseline HbA1c concentration as a covariate, treatment, country, week of visit, and treatment-by-week interaction as fixed effects, and participant and error as random effects.

Time frame: Baseline, 12 weeks

Number of Participants Who Achieve a Target HbA1c Concentration of Less Than 7% or Less Than or Equal to 6.5% at 24 Weeks

Time frame: 24 weeks

Change in the Fasting Plasma Glucose Concentration From Baseline to 12 Weeks and 24 Weeks

The least squares (LS) mean was estimated from a mixed-effects model with repeated measures (MMRM) that included baseline fasting plasma glucose value as a covariate, treatment, country, baseline HbA1c stratification level, week of visit, and treatment-by-week interaction as fixed effects, and participant and error as random effects.

Data from ClinicalTrials.gov

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For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Mar del Plata, Argentina

Ramos Mejía, Argentina

Porto Alegre, Brazil

São Paulo, Brazil

Changzhou, China

Harbin, China

Alexandria, Egypt

Cairo, Egypt

Jaipur, India

Visakhapatnam, India

...and 8 more locations

Time frame: Baseline, 12 weeks, and 24 weeks

7-point Self-Monitored Blood Glucose (SMBG) Profiles at 12 Weeks and 24 Weeks

7-point Self-monitored Blood Glucose (SMBG) Profiles are measures of blood glucose taken 7 times a day at the morning pre-meal, morning 2-hours post-meal, midday pre-meal, midday 2-hours post-meal, evening pre-meal, evening 2-hours post-meal, and 0300 hour \[3 am\]. Each participant took measures on 3 non-consecutive days and the average was calculated for each of the 7 time points. The mean of the 7-point averages was calculated for all the participants at baseline, Weeks 12 and 24. The least squares (LS) mean was estimated from mixed-effects model with repeated measures that included the baseline value of the variable as a covariate, treatment, country, baseline glycosylated hemoglobin A1c (HbA1c)stratification level, week of visit, and treatment-by-week interaction as fixed effects, and participant and error as random effects.

Time frame: 12 weeks, 24 weeks

Glycemic Variability From the 7-point Self-Monitored Blood Glucose (SMBG) Profiles at 12 Weeks and 24 Weeks

The 7-point SMBG profile was calculated as the average blood glucose concentration across the 7 pre-specified time points in a day that was then averaged over 3 non-consecutive days in the 2 weeks prior to the 12 week visit and 24 week visit. Glycemic variability was calculated as the standard deviation of the 7-point SMBG profiles. Standard deviation was first calculated for each day and then averaged over 3 non-consecutive days for each visit. The least squares (LS) mean was estimated from mixed-effects model with repeated measures that included the baseline value of the variable as a covariate, treatment, country, baseline glycosylated hemoglobin A1c (HbA1c)stratification level, week of visit, and treatment-by-week interaction as fixed effects, and participant and error as random effects.

Time frame: 12 weeks, 24 weeks

Daily Insulin Dose: Total, Basal, and Prandial at 12 Weeks and 24 Weeks

Time frame: 12 weeks, 24 weeks

Change in Weight From Baseline to 12 Weeks and 24 Weeks

The least squares (LS) mean was estimated from a mixed-effects model with repeated measures (MMRM) that included baseline weight as a covariate, treatment, country, baseline glycosylated hemoglobin A1c (HbA1c) stratification level, week of visit, and the treatment-by-week interaction as fixed effects, and participant and error as random effects.

Time frame: Baseline, 12 weeks, 24 weeks

The Number of Participants With a Hypoglycemic Episodes (Incidence)

A hypoglycemic episode was defined as an event associated with 1) reported signs and symptoms of hypoglycemia, and/or 2) a documented blood glucose (BG) concentration of \<= 70 milligrams per deciliter \[mg/dL, 3.9 millimoles per liter (mmol/L)\].

Time frame: Baseline through 24 weeks

Insulin Treatment Satisfaction Questionnaire (ITSQ) Score at 24 Weeks

ITSQ: validated instrument containing 22 items which are measured on a 7-point scale: 1 (no bother at all) to 7 (a tremendous bother) used to assess insulin treatment satisfaction. Items are divided into 5 domains: Inconvenience of Regimen (5 items: domain score range 5 to 35), Lifestyle Flexibility (3 items: domain score range 3 to 21), Glycemic Control (3 items: domain score range 3 to 21), Hypoglycemic Control (5 items: domain score range 5 to 35), Insulin Delivery Device (6 items: domain score range 6 to 42) lower scores reflect better outcome. ITSQ Total Overall Score ranged from 22 to 154. Raw domain scores transformed on 0-100 scale, where transformed domain score = 100×\[(7-raw domain score)/6\]. Higher scores indicate better treatment satisfaction. Least squares (LS) mean estimated from analysis of covariance (ANCOVA) model that included baseline score as covariate and treatment, glycosylated hemoglobin A1c (HbA1c) stratum, and country as fixed effects.

Time frame: 24 weeks

Perceptions About Medications-Diabetes 21 (PAM-D21) Questionnaire Score at 24 Weeks

PAM-D21 is a validated questionnaire consisting of 21 items to assess a participant's perceptions about their diabetes treatment regimens and perceived emotional and physical side-effects. The PAM-D21 consists of 4 subscales: Convenience/Flexibility (items 1 to 3); Perceived Effectiveness (items 4 to 6); Emotional Effects (items 7 to 11); and Physical Effects (items 12 to 21). Item scores range from 1 (none of the time) to 4 (all of the time). Subscale scores were linearly transformed to a 0-100, with higher score corresponds to better perceptions about diabetes medications. The least squares (LS) mean was estimated from an analysis of covariance (ANCOVA) model that included baseline score as a covariate and treatment, glycosylated hemoglobin A1c (HbA1c) stratum, and country as fixed effects.

Time frame: 24 weeks

The Rate of Hypoglycemic Episodes

The hypoglycemia rate per 30 days was calculated as the number of episodes reported for the interval between visits and during the study divided by the number of days in the given interval and multiplied by 30.

Time frame: Baseline through 24 weeks

The Number of Participants With Severe Hypoglycemic Episodes

The number of participants who had a severe hypoglycemic episode anytime during the study. Severe hypoglycemia was defined as any event in which the participant required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions.

Time frame: Baseline through 24 weeks