Comparison of Two Approaches to Insulin Therapy in Patients With Type 2 Diabetes (IOOX)

Study Overview
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Brief Summary
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A study of patients with type 2 diabetes and inadequate glycemic control on two or more oral antihyperglycemic agents comparing adding insulin lispro mid mixture to the oral antihyperglycemic agents to adding insulin glargine to the oral antihyperglycemic agents.

Official Title
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Comparison of Two Approaches to Basal-Bolus Insulin Therapy in Patients With Type 2 Diabetes and Inadequate Glycemic Control on Oral Therapy: Comparison of Premixed Insulin Lispro Mid Mixture With Separate Basal and Bolus Insulin Injections

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Insulin lispro mid mixture (MM)
* Drug: Insulin glargine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have type 2 diabetes Have been receiving oral antihyperglycemic medications (OAM) without insulin including at least two of the following at maximally tolerated doses, AND meet the minimum dosing criteria shown: Metformin 1500 mg/day, Sulfonylurea 1/2 the maximum daily dose, according to package insert, Thiazolidinedione (TZD) 30 mg/day pioglitazone or 4 mg/day rosiglitazone. The OAMs also must be used in accordance with the product label Have a hemoglobin A1c greater than or equal to 7.5% and less than or equal to 12.0%. Exclusion Criteria: Are taking a TZD dose greater than what is indicated in combination with insulin according to the TZD label. Are taking any other glucose-lowering agents not mentioned in Inclusion Criterion. Have taken acarbose, miglitol, pramlintide, exenatide, repaglinide, or nateglinide in the past 6 weeks or for a total of 30 days or more in the last 24 weeks. Have a body mass index greater than 40 kg/m2. Have had more than one episode of severe hypoglycemia in the last24 weeks Are pregnant, intend to be pregnant during the course of the study or are breastfeeding Have clinically significant cardiac, renal, hematologic, oncologic, or hepatic disease

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 80 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 |
| --- | --- |
| Experimental: Insulin Lispro Mid Mixture<br>Insulin lispro mid mixture (MM) up to three times a day (TID) | Drug: Insulin lispro mid mixture (MM)<br>* Patient specific adjusted dose, three times a day (TID), subcutaneous (SC) injection x 36 weeks<br>* Other names: Mid Mix;|
| Active Comparator: Insulin Glargine<br>Insulin glargine daily with insulin lispro at mealtime (up to 3 injections) as needed. | Drug: Insulin glargine<br>* Patient specific adjusted dose, every day (QD), subcutaneous (SC) injection x 36 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemoglobin A1c (HbA1c) at 36 Week Endpoint | Level of hemoglobin A1c at endpoint. | 36 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemoglobin A1c (HbA1c) at Interval Visits | Levels of HbA1c at 12 weeks and 24 weeks and 36 weeks. | 12, 24, and 36 weeks | 
| Percentage of Patients Who Achieved Hemoglobin A1c Less Than or Equal to 6.5%, Greater Than 6.5%, Less Than 7%, Greater Than or Equal to 7%, Less Than or Equal to 7%, and Greater Than 7% at Interval Visits and Endpoint |  | 12-24-36 weeks | 
| 7-point Self-monitored Blood Glucose Profiles | Actual daily mean blood glucose levels at specified time points. | Baseline, 12-24-36 weeks | 
| Glycemic Variability | Glycemic variability was measured by mean blood glucose value (M-value), which was the mean of the intra-days self-monitoring blood glucose values, and by the mean of daily difference (MODD), which was the mean of the between-days self-monitored blood glucose values. | Baseline, 12-24-36 weeks | 
| Number of Patients With at Least One Self-reported Hypoglycemic Episode, Including Nocturnal (and Non-nocturnal) Hypoglycemia | Hypoglycemic episode defined: any time patient felt that he/she was experiencing a sign or symptom associated with hypoglycemia, or had old Roche blood glucose level <70 mg/dL even if not associated with signs, symptoms, or treatment consistent with current guidelines. Nocturnal hypoglycemia defined: any hypoglycemic event that occurred between bedtime and waking. Non-nocturnal hypoglycemia defined: any hypoglycemic event that occurred between waking and bedtime. Overall episodes: those that occurred at any time during the post-randomization visits. Endpoint: last visit interval based on LOCF. | Baseline to 36 Weeks | 
| 30-Day Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including Nocturnal and Non-Nocturnal) | Hypoglycemic episode defined: any time patient felt that he/she was experiencing a sign or symptom associated with hypoglycemia, or had old Roche blood glucose level <70 mg/dL even if not associated with signs, symptoms, or treatment consistent with current guidelines. Nocturnal hypoglycemia defined: any hypoglycemic event that occurred between bedtime and waking. Non-nocturnal hypoglycemia defined: any hypoglycemic event that occurred between waking and bedtime. Overall episodes: those that occurred at any time during the post-randomization visits. Endpoint: last visit interval based on LOCF. | Baseline to 36 Weeks | 
| Number of Patients With at Least One Severe Hypoglycemia Episode | Severe hypoglycemia was defined as hypoglycemic event that meets at least one of the following criteria: not capable of treating self and blood glucose <2.8 millimoles per liter (mmol/L); not capable of treating self, blood glucose is missing and prompt recovery after oral carbohydrate or glucagon or intravenous glucose; hypoglycemic event outcome was coma, hopitalization, emergency room visit, or automobile accident. The overall category is a severe hypoglycemic event that occurred at any time during the post-randomization visits. Endpoint: last visit interval based on LOCF. | Baseline to 36 Weeks | 
| Endpoint Insulin Dose Per Body Weight; Total, Basal, and Prandial | Total daily insulin dose adjusted for body weight (Units of insulin per kilogram per day [U/kg/day]) was assessed. Basal insulin is the amount of insulin required to manage normal daily blood glucose fluctuations. Prandial insulin is taken at meal time. Insulin glargine is a basal insulin and insulin lispro is a prandial insulin. Insulin lispro mid-mix is a 50/50 mixture of a basal insulin and insulin lispro. Endpoint: last visit interval based on LOCF. | 36 Weeks | 
| Endpoint Insulin Dose; Total, Basal, and Prandial | Total daily insulin dose (Units of insulin per day [U/day]) was assessed. Basal insulin is the amount of insulin required to manage normal daily blood glucose fluctuations. Prandial insulin is taken at meal time. Insulin glargine is a basal insulin and insulin lispro is a prandial insulin. Insulin lispro mid-mix is a 50/50 mixture of a basal insulin and insulin lispro. Endpoint: last visit interval based on LOCF. | 36 Weeks | 
| Number of Insulin Injections Per Day |  | Weeks 12, 24, 30, 36 | 
| Change From Baseline in Absolute Body Weight at 36 Week Endpoint | Change in body weight was calculated as weight at endpoint (last observation carried forward) minus weight at baseline. | Baseline, 36 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes, type 2