A Comparison Study of Basal Bolus Therapies Together With Lispro Insulin in Type 2 Diabetes Patients

Study Overview
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Brief Summary
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This study is designed to look at if a basal bolus regimen of insulin lispro protamine suspension (ILPS) provides the same glycemic control as a basal bolus regimen of insulin glargine (when one basal bolus regimen is injected once daily together with insulin lispro injected 2-3 times daily).

Official Title
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A Prospective Randomized Trial to Compare Basal Bolus Therapies That Use Either Insulin Lispro Protamine Suspension or Insulin Glargine Together With Lispro Insulin in Patients With Type 2 Diabetes

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Insulin Glargine
* Drug: Insulin Lispro Protamine Suspension (ILPS)
* Drug: Insulin Lispro


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diabetes Mellitus, Type 2 Have been receiving metformin and at least one other oral antihyperglycemic medication (sulfonylurea or thiazolidinedione) with insulin for at least 3 months prior to Visit 1 (Screening) Hemoglobin A1C (HbA1c) greater than or equal to 7.5% and less than or equal to 11.0% Body Mass Index (BMI) greater than or equal to 25 and less than or equal to 45 kg/m^2 Capable and willing to follow the protocol Give written consent Exclusion Criteria: Are taking any glucose-lowering agents (other than those listed in the inclusion criteria above) Have a history of severe hypoglycemia in the past 6 months Are pregnant or may become pregnant Women who are breastfeeding Have significant cardiac disease Have significant renal or liver disease Undergoing therapy for a malignancy Contraindications to the study medications Have an irregular sleep/wake cycle Have a serious disease or any condition considered by the investigator to be exclusionary

Ages Eligible for Study
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Minimum Age: 18 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: Glargine<br>Glargine plus Insulin Lispro (2-3 injections) | Drug: Insulin Glargine<br>* patient glucose-level dependent, injection, once daily in the evening, 24 weeks<br>Drug: Insulin Lispro<br>* subcutaneous injections prior to meals, 24 weeks<br>|
| Experimental: ILPS<br>Insulin Lispro Protamine Suspension (ILPS) plus Insulin Lispro (2-3 injections) | Drug: Insulin Lispro Protamine Suspension (ILPS)<br>* patient glucose-level dependent, injection, once daily in the evening, 24 weeks<br>* Other names: LY275585;Drug: Insulin Lispro<br>* subcutaneous injections prior to meals, 24 weeks<br>|

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) to Week 24 | Least Squares Mean (LSMean) values reported in the table were controlled for treatment, country, and baseline HbA1c value. | Baseline, Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HbA1c at Week 12 and Week 24 | LSMean values presented were controlled for treatment, country, baseline HbA1C value and week. | Baseline, Week 12, Week 24 | 
| Percentage of Participants With HbA1c Less Than 7.0% and Less Than or Equal to 6.5% at Endpoint |  | Week 24 | 
| 7-point Self-monitored Blood Glucose Profiles (SMBG) at Endpoint | LSMean values presented were controlled for treatment, country, and baseline HbA1C value. SMBG at morning pre-meal, morning postprandial, midday pre-meal, midday postprandial, evening pre-meal, evening postprandial, 0300 hours. Postprandial glucose is measured 2 hours after the start of the meal. | 24 weeks | 
| Glycemic Variability at Endpoint | LSMeans were controlled for treatment and country grouping (Mediterranean, rest of Europe). Glycemic variability was assessed as the standard deviations of 4 fasting SMBG samples, 4 post-breakfast measurements, 4 post-lunch measurements, 4 post-evening meal measurements. | Week 24 | 
| Rate Of All Self-reported Hypoglycemic Episodes | Rate of self-reported hypoglycemic episodes, all, non-nocturnal,and nocturnal, severe, documented ≤3.9 mmol/L and ≤3.0 mmol/L. Rate=episodes/30 days/patient/. Episode=any time a patient has a symptom associated with hypoglycemia or blood glucose level of ≤70 mg/dL,even if not associated with symptoms.Overall=any time post-randomization in the study period. Nocturnal=Episode between bedtime and waking. Non-Nocturnal=Episode between waking and bedtime.Severe:episode in which patient requires assistance,and has glucose <50 mg/dL or prompt recovery after oral carbohydrate, glucagon, or IV glucose. | Baseline through Week 24 | 
| Percentage of Participants With Self-Reported Hypoglycemic Episodes | Episode=any time a patient feels that he/she is experiencing a sign or symptom associated with hypoglycemia or has a blood glucose level of ≤70 mg/dL, even if not associated with signs,symptoms, or treatment. Overall=any time post-randomization visits in the study period. Nocturnal=Episode that occurs between bedtime and waking. Non-Nocturnal=Episode occurring between waking and bedtime. Severe=episode with symptoms of neuroglycopenia in which patient requires assistance,and has blood glucose value <50 mg/dL or prompt recovery after oral carbohydrate, glucagon, or intravenous glucose. | Baseline through Week 24 | 
| Number of Participants With Adverse Events (AE) | A listing of adverse events is located in the Reported Adverse Event module. | Baseline through Week 24 | 
| Change in Body Weight From Baseline to Week 24 | LSMean values presented were controlled for treatment, country, and baseline HbA1C value. | Baseline, Week 24 | 
| Total Daily Insulin Dose at Endpoint | LSMean values presented were controlled for treatment, country, and baseline HbA1C value. | Week 24 | 
| Number of Injections of Insulin at Week 24 |  | Week 24 |