Official Title: “A Comparison of Insulin Lispro MM Intensive Mixture Therapy With Progressive Dose-Titration of Insulin Lispro LM or Biphasic Insulin Aspart 30/70”

Investigation into patients with type 2 diabetes mellitus not achieving adequate glycemic control while treated with combination of premixed insulin analogue formulations BID and metformin will be randomly assigned to follow one of two insulin treatment strategies used in combination with metformin administration. The aim of the trial is to try to achieve optimal metabolic control and explore full therapeutic potential of the strategies, patients in both arms will follow progressive insulin dose titration algorithms for 16 weeks.

Study Type: Interventional

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

Intervention(s) in this Clinical Trial

• Drug: Insulin Lispro Intensive Mixture Therapy (MM/LM TID)
• Drug: Dose-Titration of Lispro LM or Biphasic Insulin Aspart 30/70

Primary Measures

• To compare efficacy of two insulin treatment strategies in patients with type 2 Diabetes

Secondary Measures

• To evaluate HbA1c , 2-hour postprandial blood glucose, overall safety, and compare the total daily insulin dose in the treatment groups.

Inclusion Criteria:

• 1. Have type 2 diabetes (World Health Organization [WHO] classification).
• 2. Are at least 30 years of age and less than 75 years of age.
• 3. Have been receiving hypoglycemic treatment with premixed insulin analogue (either with insulin lispro LM or biphasic insulin aspart 30/70) administered twice daily in combination with at least 1500 mg of metformin per day for at least 60 days immediately prior to the study.
• 4. Have a hemoglobin A1c 1.2 to 1.8 times the upper limit of the normal reference range at the local laboratory at Visit 1 or Have at least 6 of 9 of the postprandial blood glucose values recorded in the period between Visit 1 and Visit 2 exceeding 180 mg/dl
• [10.0 mmol/l].
• 5. As determined by the investigator, are capable and willing to continue injections of insulin while continuing to use metformin as specified in inclusion Criterion [3], learn how to use the insulin injection pen(s), perform self blood glucose monitoring, adjust doses of insulin according to the algorithm provided, use the patient diary as required for this protocol, be receptive to diabetes education
• 6. Have given written informed consent to participate in this study in accordance with local regulations.

Exclusion Criteria:

• 7. Are taking any other OAMs not mentioned in inclusion criterion [3].
• 8. Have a body mass index greater than 40 kg/m2.
• 9. Have had more than one episode of severe hypoglycemia within 6 months prior to entry into the study.
• 10. 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.
• 11. Are women who are breastfeeding.
• 12. Have cardiac disease with functional status that is Class III or IV (American Heart
• Association)
• 13. Have congestive heart failure.
• 14. Have a history of renal transplantation or are currently receiving renal dialysis.
• 15. Have obvious clinical signs or symptoms, or laboratory evidence, of liver disease (ALT or AST greater than 2 times the upper limit of the reference range as defined by the local laboratory).
• 16. Are undergoing therapy for a malignancy, other than basal cell or squamous cell skin cancer.
• 17. Have known hypersensitivity or allergy to any of the study drugs or excipients of the study drugs.
• 18. Have had a blood transfusion or severe blood loss in the opinion of the investigator within 3 months prior to Visit 1 or have known hemoglobinopathy, hemolytic anemia, or sickle cell anemia.
• 19. Are receiving chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy (excluding topical and inhaled preparations) or have received such therapy within the 4 weeks immediately preceding Visit 1.
• 20. Have an irregular sleep/wake cycle (for example, patients who sleep during the day and work during the night).
• 21. Have any other condition (including known drug or alcohol abuse, psychiatric disorder) that precludes the patient from following and completing the protocol.
• 22. Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.
• 23. Are investigator site personnel directly affiliated with the study, or are immediate family of investigator site personnel directly affiliated with the study. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.
• 24. Are employed by Lilly (that is, employees, temporary contract workers, or designees responsible for conducting the study). Immediate family of Lilly employees may participate in Lilly-sponsored clinical trials, but are not permitted to participate at a Lilly facility. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.
• 25. Have serum creatinine at a level that contraindicates metformin use according to the country-specific metformin product label.
• 26. Have known metabolic or lactic acidosis.
• 27. Have any condition associated with hypoperfusion, hypoxemia, dehydration, or sepsis.
• 28. Have had a radiologic contrast study within 48 hours prior to entry in the study or plan to have these procedures or surgery performed during the study.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 30 Years

Maximum Age for this Clinical Trial: 75 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  

Overall Contact: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00393705

Study ID Number: 10916

ClinicalTrials.gov Identifier: NCT00393705

Health Authority: Poland: Ministry of Scientific Research and Information Technology

Lilly Clinical Trial Registry