Comparison of Two Basal Insulins for Patients With Type 2 Diabetes Taking Oral Diabetes Medicines and Exenatide

Study Overview
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Brief Summary
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This study will compare insulin lispro protamine suspension (ILPS) and insulin glargine in combination with the patient's oral diabetes medications and exenatide, for their ability to control blood sugar in patients with type 2 diabetes.

Official Title
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A Randomized Trial Comparing Insulin Lispro Protamine Suspension With Insulin Glargine in Subjects With Type 2 Diabetes on Oral Antihyperglycemic Medications and Exenatide

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Insulin Lispro Protamine Suspension
* Drug: Insulin Glargine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have type 2 diabetes Must be at least 18 years of age and less than 75 years of age Must be taking exenatide 10 micrograms twice a day (BID) for at least 3 months Must be taking one of the following oral diabetes medication regimens for at least 3 months: (1) metformin (2) metformin + sulfonylurea (3) metformin + thiazolidinedione (TZD). Doses must be at or above the following: Metformin--1500 mg/day, Sulfonylurea--1/2 the maximum daily dose according to the product label, TZD--30 mg/day pioglitazone Must have a hemoglobin A1C greater than or equal to 7.0% and less than or equal to 10.0% Exclusion Criteria: Must not have used insulin on a regular basis during the past 2 years Must not have taken any glucose-lowering medications not included in the inclusion criteria in the past 3 months Must not have had more than one episode of severe hypoglycemia in the past 6 months Must not have clinically significant hematologic, oncologic, renal, cardiac, hepatic, or gastrointestinal disease Must not be pregnant or intend to get pregnant during the course of the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ILPS<br>Insulin Lispro Protamine Suspension (ILPS) | Drug: Insulin Lispro Protamine Suspension<br>* Administered subcutaneously once a day at bedtime<br>* Other names: LY275585[P];|
| Active Comparator: Glargine<br>Insulin Glargine | Drug: Insulin Glargine<br>* Administered subcutaneously once a day at bedtime<br>* Other names: Lantus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Hemoglobin A1C (HbA1c) at Endpoint (Last Observation Carried Forward [LOCF]) | Least squares mean values were controlled for Baseline + Baseline HbA1c Group + Baseline sulfonylurea (SU) Group. | Baseline, Endpoint (LOCF) up to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Actual Hemoglobin A1C at 24 Weeks and Endpoint (LOCF) | Least squares mean values were controlled for Baseline + Baseline HbA1c Group + Baseline SU Group. | 24 weeks, Endpoint (LOCF) up to 24 weeks | 
| Change From Baseline in Hemoglobin A1C at 24 Weeks and Endpoint (LOCF) | Least squares mean values were controlled for Baseline + Baseline HbA1c Group + Baseline SU Group. | Baseline, 24 Weeks, Endpoint (LOCF) up to 24 weeks | 
| Percentage of Participants With Hemoglobin A1C Less Than 7.0% and Hemoglobin A1C Less Than or Equal to 6.5% |  | Weeks 12, 18, 24 and Endpoint (LOCF) up to 24 weeks | 
| 7-Point Self-Monitored Blood Glucose (SMBG) Profiles at Baseline and Endpoint (LOCF) | SMBG at morning pre-meal, morning post-prandial, midday pre-meal, midday post-prandial, evening pre-meal, evening postprandial, 0300 hours. Post-prandial glucose is measured 2 hours after the start of the meal. | Baseline, Endpoint (LOCF) up to 24 weeks | 
| Glycemic Variability at Baseline and Endpoint (LOCF) | Glycemic variability was defined as the standard deviation (SD) of a participant's intra-day 7-point, self-monitored, blood glucose. Mean SD was calculated based on the SD for each participant in the study. | Baseline, Endpoint (LOCF) up to 24 weeks | 
| Incidence of Self-reported Hypoglycemic Episodes (All, Non-Nocturnal, Nocturnal, and Severe) | Overall:any time after randomization.Episode:any time patient experienced sign/symptom associated with hypoglycemia, or had blood glucose level ≤70 mg/dL. Non-nocturnal:any episode that occurred between waking and bedtime. Nocturnal:any episode that occurred between bedtime and waking.Severe:episode with symptoms consistent with neuroglycopenia in which patient requires assistance,and is associated with:blood glucose value <50 mg/dL or prompt recovery after oral carbohydrate, glucagon, or intravenous glucose.Incidence(%)=(Number of patients experiencing episodes/number of patients in arm)*100. | Baseline to Endpoint (LOCF) up to 24 weeks | 
| Rate of All, Non-Nocturnal, and Nocturnal Self-Reported Hypoglycemic Episodes (Adjusted for One Year) | Rate of self-reported hypoglycemic episodes, all, non-nocturnal, and nocturnal, at Endpoint (LOCF) and overall. Rate is reported as episodes/participant/365 days. Episode = any time participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia or has a blood glucose level of ≤70 mg/dL, even if it was not associated with signs, symptoms, or treatment. Overall=any time during the post-randomization visits within the study period. Nocturnal=Any episode that occurs between bedtime and waking. Non-Nocturnal=Any episode that occurs between waking and bedtime. | Baseline to Endpoint (LOCF) up to 24 weeks | 
| Actual Body Weight at Baseline and Endpoint (LOCF) |  | Baseline, Endpoint (LOCF) up to 24 weeks | 
| Change From Baseline in Body Weight at Endpoint (LOCF) |  | Baseline, Endpoint (LOCF) up to 24 weeks | 
| Total Daily Insulin Dose at Endpoint (LOCF) |  | Endpoint (LOCF) up to 24 weeks |