Official Title: “The Durability of Twice-Daily Insulin Lispro Low Mixture Compared to Once-Daily Insulin Glargine When Added to Existing Oral Therapy in Patients With Type 2 Diabetes and Inadequate Glycemic Control”

This study will compare insulin lispro low mixture [LM] and insulin glargine in combination with the patient's oral diabetes medicines for their ability to control blood sugar in patients with type 2 diabetes and compare insulin lispro LM to insulin glargine with regard to the length of time that the overall blood sugar can be controlled.

This study will also determine whether the safety of insulin lispro LM and any side effects that might be associated with it are different from those observed with insulin glargine in combination with the patient's oral diabetes medications.

The addendum study will compare how different insulin treatments work to control blood sugar in patients whose diabetes could not be controlled by either insulin lispro LM or insulin glargine.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: December 2009

Intervention(s) in this Clinical Trial

• Drug: Glargine
  • Insulin glargine SC once daily for up to 5 years
• Drug: Humalog Low Mix
  • Humalog LM SC twice daily for up to 5 years

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • Insulin glargine once daily
• Experimental: 2
  • Humalog Low Mix twice daily SC

Primary Measures

• INITIATION: Comparison of endpoint A1C after 6 months of starter insulin therapy with either insulin lispro low mixture [LM] twice-daily or insulin glargine.
  • Time Frame: 6 months
    Safety Issue?: Yes
• MAINTENANCE: Comparison of the duration of time that each starter insulin regimen is able to maintain A1C at goal.
  • Time Frame: 6 months - 5 years
    Safety Issue?: Yes
• ADDENDUM: Comparison of endpoint A1C after 6 months of second step intensification regimens in patients who have not achieved control during 6 months of starter insulin therapy.
  • Time Frame: 6 months
    Safety Issue?: Yes

Secondary Measures

• INITIATION+MAINTENANCE: Change in HbA1c from baseline to 6 months (initiation phase endpoint), baseline to maintenance phase endpoint and 6 months to maintenance phase endpoint
  • Time Frame: 6 months - 5 years
    Safety Issue?: Yes
• MAINTENANCE+ADDENDUM: Percentage of patients with A1C < or = 7.0% and A1C < or = 6.5%
  • Time Frame: 6 months - 5 years
    Safety Issue?: Yes
• MAINTENANCE+ADDENDUM: HbA1c at specified visits and endpoint
  • Time Frame: Visits 1, 2, 4, 6-14, A3, A4, Early Term
    Safety Issue?: Yes
• MAINTENANCE+ADDENDUM: Blood glucose measurements during 7-point profiles at specified visits and endpoint
  • Time Frame: Visits 2, 4, 6, 8, 10, 12, 14, A3, A4,Early Term
    Safety Issue?: Yes
• MAINTENANCE+ADDENDUM: Absolute and incremental weight change
  • Time Frame: Every visit, endpoint
    Safety Issue?: No
• MAINTENANCE+ADDENDUM: Insulin dose (24 hour total IU and total IU/kg body weight) at each visit and endpoints
  • Time Frame: Every visit, endpoint
    Safety Issue?: No
• MAINTENANCE+ADDENDUM: Incidence as well as rate of self-reported hypoglycemic episodes
  • Time Frame: Every visit
    Safety Issue?: Yes
• ADDENDUM: Change in HbA1c from point of second randomization to endpoint
  • Time Frame: Endpoint
    Safety Issue?: No
• MAINTENANCE+ADDENDUM: 1,5-Anhydroglucitol
  • Time Frame: Visits 2, 6, 10, 14, A4 or Early Term
    Safety Issue?: No

Inclusion Criteria:

• Must have type 2 diabetes.
• Must be at least 30 and less than 80 years of age at the time of Visit 1.
• Must be on at least two oral antidiabetes medications for at least 90 days.
• Must have an A1C 1.2 to 2.0 times the upper limit of normal reference range at the local lab.

Exclusion Criteria:

• Must not have used insulin on a regular basis in the last 12 months.
• Must not have had more than one episode of severe hypoglycemia in the last 24 weeks.
• Must not have a body mass index (BMI) or greater than 45 (morbid obesity).
• Must not have clinically significant hematologic, oncologic, renal, cardiac, hepatic, or gastrointestinal disease.
• Must not be pregnant or intend to get pregnant during course of the study.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 30 Years

Maximum Age for this Clinical Trial: 79 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Eli Lilly and Company

Overall Clinical Trial Officials and Contacts

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Study Director Eli Lilly and Company  

Information obtained from ClinicalTrials.gov on November 19, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00279201

Study ID Number: 10455

ClinicalTrials.gov Identifier: NCT00279201

Health Authority: United States: Food and Drug Administration

Lilly Clinical Trial Registry