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

• Actual and Change From Baseline to 12 Week and 24 Week Endpoint in HbAlc Value [ Time Frame: Baseline, 12 Weeks, 24 Weeks ] [ Designated as safety issue: No ]
• Percentage of Patients With HbAlc Less Than 7.0 Percent and HbAlc Less Than or Equal to 6.5 Percent at Endpoint [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Percentage of patients achieving Hemaglobin A1c (HbA1c) targets of less than 7% and less than or equal to 6.5% at endpoint.
• Glycemic Variability at Endpoint [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  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.
• 7-Point Self-Monitored Blood Glucose (SMBG) Profile at Endpoint [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Actual measurements and daily mean blood glucose levels at endpoint.
• Number of Participants With Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe Hypoglycemia) Overall [ Time Frame: Baseline to 24 weeks ] [ Designated as safety issue: Yes ]
  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.
• 1-Year Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe) Overall [ Time Frame: Baseline to 24 weeks ] [ Designated as safety issue: Yes ]
  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.
• 30-Day Adjusted Rates of Self-Reported Hypoglycemic Episodes (Including All, Nocturnal, and Severe) Overall [ Time Frame: Baseline to 24 Weeks ] [ Designated as safety issue: Yes ]
  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.
• Change in Absolute Body Weight (kg) From Baseline to 24 Week Endpoint [ Time Frame: Baseline, 24 weeks ] [ Designated as safety issue: Yes ]
• Total Daily Insulin Dose (Units) at Endpoint [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Insulin dose at endpoint was analyzed by 24-hour total daily insulin (units).
• Total Daily Insulin Dose Per Body Weight (Units/Kilograms) at Endpoint [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]
  Insulin dose at endpoint was analyzed by 24-hour total daily insulin per body weight (units/kilograms).

• Actual and change from baseline HbAlc value. [ Time Frame: At weeks 12 and 24 ]
• Percentage of patients with HbAlc less than 7.0 percent and HbAlc less than or equal to 6.5 percent at endpoint. [ Time Frame: 24 weeks ]
• 7-point self-monitored blood glucose (SMBG) profile and glycemic variability from these profiles at endpoint. [ Time Frame: 24 weeks ]
• The incidence, 30 day adjusted rate, and 1 year adjusted rate of reported hypoglycemic episodes (throughout the study and at endpoint) including nocturnal and non-nocturnal; and severe hypoglycemia. [ Time Frame: 24 weeks ]
• Absolute body weight (kg) and incremental weight change from baseline to endpoint. [ Time Frame: 24 weeks ]
• Treatment-emergent adverse events (TEAEs). [ Time Frame: 24 weeks ]
• Total daily insulin dose. [ Time Frame: 24 weeks ]

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.

• Drug: Insulin Lispro Protamine Suspension
  Patient adjusted dose, once daily (QD) or twice daily (BID), injected subcutaneous (SC) x 24 weeks
  Other Names:

  • Insulin Lispro Protamine Suspension (ILPS)
  • Neutral Protamine Lispro (NPL)
  • Humalog
• Drug: Insulin Glargine
  Patient adjusted dose, once daily (QD), injected subcutaneous (SC) x 24 weeks

• Experimental: Lispro
  Insulin Lispro protamine suspension: Patient adjusted dose, once daily (QD) or twice daily (BID), injected subcutaneous (SC) x 24 weeks
  Intervention: Drug: Insulin Lispro Protamine Suspension
• Active Comparator: Glargine
  Insulin glargine: Patient adjusted dose, once daily (QD), injected subcutaneous (SC) x 24 weeks
  Intervention: Drug: Insulin Glargine

• Strojek K, Shi C, Carey MA, Jacober SJ. Addition of insulin lispro protamine suspension or insulin glargine to oral type 2 diabetes regimens: a randomized trial. Diabetes Obes Metab. 2010;12(10):916-922.
• Qu Y, Jacober SJ, Zhang Q, Wolka LL, DeVries JH. Rate of hypoglycemia in insulin-treated patients with type 2 diabetes can be predicted from glycemic variability data. Diabetes Technol Ther. 2012 Nov;14(11):1008-12. doi: 10.1089/dia.2012.0099.

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.