Avandia™ + Amaryl™ or Avandamet™ Compared With Metformin (AVALANCHE™ Study)
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Avandamet; Avandia and Amaryl; Metformin
Intervention description: Avandamet 2 / 500 mg twice daily titration up to 4 mg / 1000 mg twice daily compared to Avandia 4 mg and Amaryl 1 mg once daily over 6 months or compared to Metformin 500 mg twice daily up to 1000 mg over 6 months.; Avandia 4 mg and Amaryl 1 mg once daily compared to Avandamet 2 / 500 mg twice daily titration up to 4 mg / 1000 mg twice daily, or compared to Metformin 500 mg twice daily up to 1000 mg over 6 months.; Metformin 500 mg twice daily up to 1000 mg over 6 months compared to Avandia 4 mg and Amaryl 1 mg once daily or compared to Avandamet 2 / 500 mg twice daily titration up to 4 mg / 1000 mg twice daily
Intervention MeSH terms: Metformin; Glimepiride; Rosiglitazone; Maleic acid
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 391.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      The incidence of type 2 diabetes is on the increase. According to recent Canadian Diabetes
      Association guidelines glucose control, based on the A1C measurement, needs to be achieved
      within a 6-12 month period of time after the initial diagnosis of type 2 diabetes. The
      guidelines on the use of antihyperglycemic agents identify the potential benefits of
      sub-maximal oral combination therapy in order to achieve more rapid and improved glycemic
      control compared with higher dose monotherapy. Furthermore, many patients on prolonged oral
      antihyperglycemic monotherapy who then start on combination therapy may not achieve the
      required target glycemic control. Indeed early initiation of combination therapies may be
      necessary to achieve and maintain glycemic targets because of the progressive deterioration
      of pancreatic β cell function and glycemic control.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Type 2 diabetes patients

          2. 18 - 75 years old

          3. Type 2 diabetes mellitus (DM) drug naïve or on submaximal oral monotherapy < 3 years

          4. A1C criteria at screening:

               1. 7.1-10% for drug naïve patients after failure of diet control and life-style
                  modification

               2. 7.1 - 9% on single therapy (e.g. not more 10 mg of Glyburide or 4 mg of Amaryl™
                  or 1000mg of Metformin) who will start after 2 weeks wash-out. During wash out
                  the following will be done: i) diet and life style modification ii) Angiotensin
                  converting enzyme inhibitor (ACE), aspirin (80 mg), and statin if appropriate

          5. Signed informed consent

        Exclusion Criteria:

          1. Type 1 diabetes

          2. Subjects currently treated with insulin

          3. Subject treated for previous 3 month with any thiazolidinedione (TZD)

          4. Evidence of clinically significant concomitant illnesses which are not controlled by
             medication and/or may limit participation in the study as judged by the investigator

          5. Subjects who have hypersensitivity to any components of study drugs

          6. Participation in a clinical trial and/or intake of an investigational drug within 30
             days prior to screening.

          7. Pregnant or nursing females

          8. Females of childbearing potential who are not on adequate birth control

          9. Liver enzymes (Alanine Aminotransferase (ALT) > 2.5 times upper limit of normal)

         10. Renal impairment: serum creatinine ≥ 136umol/L (males) and ≥ 124 umol/L (females)

         11. Congestive Heart Failure (CHF class III/IV)

         12. Weight >160 kg