Pre-Mix Insulin Lispro Treatment for Type 2 Diabetes Patients Who Consume a Light Breakfast

Study Overview
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Brief Summary
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This study is designed to look at how best to start and then gradually intensify (as needed) the insulin lispro premix regimen in type 2 diabetes patients who consume a light breakfast.

Official Title
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Comparison of Premixed Insulin Lispro Low-Mixture and Mid-Mixture Regimens With Separate Basal and Bolus Insulin Injections in Patients With Type 2 Diabetes With Inadequate Glycemic Control on Oral Therapy Who Consume Light Breakfast

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Insulin Glargine
* Drug: Insulin Lispro Premix (mid-mixture and low-mixture)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diabetes Mellitus, Type 2 have been receiving metformin plus at least one other oral antihyperglycemic medication (OAM) (sulfonylurea or Thiazolidinedione [TZD]) without insulin, for at least 90 days prior to Visit 1 glycosylated hemoglobin (HbA1c) greater than or equal to 7.0% and less than 11.0% regularly consume a light breakfast (less than 15% of total daily calorie intake) capable and willing to follow the protocol give written consent Exclusion Criteria: are taking a TZD whose country label does not allow in combination with insulin are taking any glucose-lowering agents (other than specified in the inclusion criteria above) have a body mass index greater than 40 kg/m^2 have a history of severe hypoglycemia in past 24 weeks 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 study medications have an irregular sleep/wake cycle

Ages Eligible for Study
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Minimum Age: 30 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: Glargine<br>Glargine +/- 1,2 or 3 injections of insulin lispro plus oral antihyperglycemic medications (OAMs) | Drug: Insulin Glargine<br>* patient glucose-level dependent, injection, as needed per patient glucose level, 48 weeks<br>|
| Experimental: Premixed Insulin Lispro<br>Premixed Insulin Lispro (mid-mixture or low-mixture) 1,2 or 3 injections plus OAMs | Drug: Insulin Lispro Premix (mid-mixture and low-mixture)<br>* patient glucose level dependent, injection, as needed per patient glucose level, 48 weeks<br>* Other names: LY275585;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline Adjusted Glycosylated Hemoglobin (HbA1c) at Endpoint | Least Squares Mean (LSMean) values were adjusted based on a fixed effect linear regression model: HbA1c = Treatment + Country + HbA1c baseline value + Ramadan holiday between Visit 10 (Week 36) and Visit 12 (Week 48) (yes/no) in per-protocol (PP) population. | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Using Each Possible Final Insulin Regimen | Insulin Regimens: Lispro: Mid-Mix (MM) before noon; Low-Mix (LM) before evening (PM); MM before noon+LM before PM; LM before morning (AM)+MM before noon + LM before PM; MM before AM +MM before noon+LM before PM Glargine: Glargine once a day (QD); Glargine QD + 1 Lispro (noon or PM); Glargine QD + 2 Lispro (noon and PM); Glargine QD + 3 Lispro. | 48 weeks | 
| HbA1c Over Time | Least Squares Mean (LSMean) values were adjusted based on a mixed effect linear regression model with a participant specific random effect: HbA1c = Treatment + Country + HbA1c baseline value + Ramadan holiday between Visit 10 (Week 36) and Visit 12 (Week 48) (yes/no) + visit + visit*treatment in Full Analysis Set (FAS) Population. | 16 weeks, 32 weeks, and 48 weeks | 
| Percentage of Patients Achieving HbA1c Less Than or Equal to 6.5% and Less Than or Equal to 7% Over Time |  | 16 weeks, 32 weeks and 48 weeks | 
| 7-point Self-monitored Blood Glucose Profiles |  | 16 weeks, 32 weeks and 48 weeks | 
| Mean Postprandial Blood Glucose Values | Mean postprandial blood glucose values were assessed using GlycoMark, which is an FDA-approved blood test measuring levels of 1,5 anhydroglucitol (1,5 AG) in serum or plasma. When 1,5 AG values decrease, serum glucose levels increase. | Baseline, 16 weeks, 32 weeks and 48 weeks | 
| Mean Daily Total, Basal and Prandial Insulin Dose |  | 16 weeks, 32 weeks and 48 weeks | 
| Body Weight Change From Baseline to Endpoint |  | baseline, 48 weeks | 
| Incidence of All Self-reported Hypoglycemic Episodes | Percentage of participants with self-reported hypoglycemic episodes at any time during the study. A hypoglycemic episode is defined as any time a 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 (3.9 mmol/L) (Roche plasma glucose) or ≤75 mg/dL (4.2 mmol/L) (IFCC Plasma Values), even if it was not associated with signs, symptoms, or treatment consistent with current guidelines (ADA 2005). | Baseline to 48 weeks | 
| Rate Per 30 Days of All Self-reported Hypoglycemic Episodes | The hypoglycemia rate between two visits will be calculated as the total number of episodes between the two visits divided by the number of days between the visits, and then multiplied by 30 days (rate per patient per 30 days). | Baseline to 48 weeks | 
| Number of Participants With Adverse Events | A summary of serious adverse events (SAEs) and all other non-serious treatment-emergent adverse events (TEAE) is located in the Reported Adverse Event Module. TEAEs are defined as events that are newly reported after randomization or reported to worsen in severity from baseline. | Baseline to 48 weeks |