Insulin Glargine Injection Treatment in Place of Thiazolidinedione (TZD), Sulfonylurea, or Metformin in Triple Agent Therapy for Type 2 Diabetes Mellitus (T2DM) Adult Subjects With Unsatisfactory Control
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Insulin Glargine; Insulin Glulisine
Intervention description: Insulin glargine administered subcutaneously once daily.; Insulin glulisine will be added after Week 12 or later for those subjects needing prandial insulin therapy (HbA1c >6.5%)
Intervention MeSH terms: Insulin; Insulin, Globin Zinc; Insulin Glargine; Insulin glulisine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 390.0
Sex: All
Minimum age: 18 Years
Maximum age: 79 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to compare the change in hemoglobin A1c (HbA1c) from baseline to
      Week 12 between the 3 treatment arms.
    

Eligibility criteria:

        Inclusion Criteria:

        Subjects meeting all of the following criteria will be considered for enrollment into the
        study:

          1. 18 to 79 years of age, inclusive

          2. Diagnosis of type 2 diabetes mellitus

          3. Continuous treatment with therapeutic dosages of a thiazolidinedione (rosiglitazone or
             pioglitazone), metformin, and a sulfonylurea daily prior to entering the study

          4. Screening HbA1c ≥ 7.0%

          5. Fasting C-peptide concentration ≥ 0.27 ng/ml

          6. Negative glutamic acid decarboxylase (GAD) antibodies

          7. Demonstrated ability and willingness to perform self-monitoring blood glucose (SMBG)
             using a plasma-referenced glucose meter and to maintain an electronic diary

          8. Demonstrated ability and willingness to use an electronic diary to record SMBG
             results, insulin doses, and hypoglycemic events.

          9. Signed, informed consent and Health Insurance Portability and Accountability Act
             (HIPAA) documentation

        Exclusion Criteria:

          1. Stroke, myocardial infarction, coronary artery bypass graft, percutaneous transluminal
             coronary angioplasty, or angina pectoris, within the last 12 months

          2. Cardiac status New York Heart Association (NYHA) III-IV

          3. Impaired renal function as shown by, but not limited to, serum creatinine ≥ 1.5 mg/dL
             for males, or ≥ 1.4 mg/dL for females

          4. Chronic use of insulin: (more than 3 weeks of continuous use) in the past 12 months

          5. Acute infection

          6. Clinically significant peripheral edema

          7. Acute or chronic history of metabolic acidosis, including diabetic ketoacidosis

          8. Clinical evidence of active liver disease, or serum alanine aminotransferase (ALT) or
             aspartate aminotransferase (AST) 2.5 times the upper limit of the normal range

          9. History of hypoglycemia unawareness

         10. Pregnancy or lactation

         11. Known hypersensitivity to insulin glargine or any of the components of Lantus®

         12. Known hypersensitivity to insulin glulisine or any of the components of Apidra®

         13. Any malignancy within the last 5 years, with the exception of adequately treated basal
             or squamous cell carcinoma of the skin or adequately treated cervical carcinoma in
             situ

         14. Current addiction or current alcohol abuse, or history of substance or alcohol abuse
             within the last 2 years

         15. Diagnosis of dementia

         16. Subject is the investigator or any sub-investigator, research assistant, pharmacist,
             study coordinator, other staff or relative thereof directly involved in the conduct of
             the protocol

         17. Mental condition rendering the subject unable to understand the nature, scope, and
             possible consequences of the study. Subject unlikely to comply with protocol, e.g.,
             uncooperative attitude, inability to return for follow-up visits, and unlikelihood of
             completing the study

         18. subject is currently taking or was treated with the following medications 3 months
             prior to screening: Byetta(exenatide), Starlix(nateglinide),Prandin (repaglinide),
             Januvia(sitagliptin), Janumet(metformin + sitagliptin)

         19. Any disease or condition that in the opinion of the investigator and/or sponsor may
             interfere with the completion of the study