Comparison of Two Basal Insulins for Patients With Type 2 Diabetes on Anti-Hyperglycemic Medications (IOPE)

Study Overview
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Brief Summary
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The purpose of this study is to examine the effectiveness and safety of insulin lispro protamine suspension (ILPS) as compared to insulin glargine as basal insulin therapy in adults with type 2 diabetes.

Official Title
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The PERSISTENT Trial: A Prospective Randomized Trial Comparing Insulin Lispro Protamine Suspension to Insulin Glargine in Patients With Type 2 Diabetes on Anti-hyperglycemic Medications

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: Have type 2 diabetes mellitus for at least 1 year. Are greater than or equal to 18 years old. Have been receiving oral antihyperglycemic medications (OAMs), without insulin, for at least 3 months immediately prior to the study and have been on stable doses of at least 2 of the following OAMs for the 6 weeks prior to Visit 1: Metformin- Sulfonylureas-Dipeptidyl peptidase-IV (DPP-IV) inhibitors-Thiazolidinediones (TZDs) Have a hemoglobin A1c (HbA1c) greater than or equal to 7.5% and less than or equal to 10.0%, as measured by a central laboratory before Visit 2. Body mass index (BMI) greater than or equal to 25 and less than or equal to 45 kg/meter squared. Exclusion Criteria: Have used insulin therapy (outside of pregnancy) any time in the past 2 years, except for short-term treatment of acute conditions, and up to a maximum of 4 weeks. Have taken any glucose-lowering medications not included in Inclusion Criterion #3; (for example, acarbose, miglitol, pramlintide, exenatide, repaglinide, or nateglinide) in the past 3 months before Visit 1. Have had more than 1 episode of severe hypoglycemia, within 6 months prior to entry into the study, or is currently diagnosed as having hypoglycemia unawareness. Have had 2 or more emergency room visits or hospitalizations due to poor glucose control in the past 6 months. Are pregnant or intend to become pregnant during the course of the study or are sexually active women of childbearing potential not actively practicing birth control by a method determined by the investigator to be medically acceptable.

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 |
| --- | --- |
| Experimental: Lispro<br>Insulin Lispro protamine suspension: Patient adjusted dose, once daily (QD) or twice daily (BID), injected subcutaneous (SC) x 24 weeks | Drug: Insulin Lispro Protamine Suspension<br>* Patient adjusted dose, once daily (QD) or twice daily (BID), injected subcutaneous (SC) x 24 weeks<br>* Other names: Humalog;|
| Active Comparator: Glargine<br>Insulin glargine: Patient adjusted dose, once daily (QD), injected subcutaneous (SC) x 24 weeks | Drug: Insulin Glargine<br>* Patient adjusted dose, once daily (QD), injected subcutaneous (SC) x 24 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to 24 Week Endpoint in Hemoglobin A1c (HbA1c) |  | Baseline, 24 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Actual and Change From Baseline to 12 Week and 24 Week Endpoint in HbAlc Value |  | Baseline, 12 Weeks, 24 Weeks | 
| Percentage of Patients With HbAlc Less Than 7.0 Percent and HbAlc Less Than or Equal to 6.5 Percent at Endpoint | Percentage of patients achieving Hemaglobin A1c (HbA1c) targets of less than 7% and less than or equal to 6.5% at endpoint. | 24 weeks | 
| Glycemic Variability at Endpoint | Glycemic variability was measured by standard deviation (SD) value of fasting blood glucose as measured by intra-patient glycemic variability (determined by the 7-point self-monitoring blood glucose (SMBG) profiles at endpoint) based on the actual morning pre-meal blood glucose. | 24 weeks | 
| 7-Point Self-Monitored Blood Glucose (SMBG) Profile at Endpoint | Actual measurements and daily mean blood glucose levels at endpoint. | 24 weeks | 
| Number of Participants With Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe Hypoglycemia) Overall | Overall: any time after randomization. Hypoglycemic: any time patient experienced sign/symptom associated with hypoglycemia, or had old Roche blood glucose level <7 mg/dL. Nocturnal: any hypoglycemic event that occurred between bedtime and waking. Severe Hypoglycemia: event with symptoms consistent with neuroglycopenia in which patient requires assistance, and is associated with either a Roche blood glucose value <2.8 millimoles/liter or prompt recovery after oral carbohydrate, glucagon, or intravenous glucose. | Baseline to 24 weeks | 
| 1-Year Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe) Overall | Overall: any time after randomization. Hypoglycemic: any time patient experienced sign/symptom associated with hypoglycemia, or had old Roche blood glucose level <7 mg/dL. Nocturnal: any hypoglycemic event that occurred between bedtime and waking. Severe: event with symptoms consistent with neuroglycopenia in which patient requires assistance, and is associated with: a Roche blood glucose value <2.8 mmol/L or prompt recovery after oral carbohydrate, glucagon, or IV glucose. 1-year adjusted rate=(total number of episodes between 2 time intervals/number of days between intervals) X 365.25 days. | Baseline to 24 weeks | 
| 30-Day Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe) Overall | Overall: any time after randomization. Hypoglycemic: any time patient experienced sign/symptom associated with hypoglycemia, or had old Roche blood glucose level <7 mg/dL. Nocturnal: any hypoglycemic event that occurred between bedtime and waking. Severe: event with symptoms consistent with neuroglycopenia in which patient requires assistance, and is associated with: a Roche blood glucose value <2.8 mmol/L or prompt recovery after oral carbohydrate, glucagon, or IV glucose. 30-day adjusted rate=(total number of episodes between 2 time intervals/number of days between intervals) X 30 days. | Baseline to 24 Weeks | 
| Change in Absolute Body Weight (kg) From Baseline to 24 Week Endpoint |  | Baseline, 24 weeks | 
| Total Daily Insulin Dose (Units) at Endpoint | Insulin dose at endpoint was analyzed by 24-hour total daily insulin (units). | 24 weeks | 
| Total Daily Insulin Dose Per Body Weight (Units/Kilograms) at Endpoint | Insulin dose at endpoint was analyzed by 24-hour total daily insulin per body weight (units/kilograms). | 24 Weeks | 

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