Avandia™ + Amaryl™ or Avandamet™ Compared With Metformin (AVALANCHE™ Study)
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 3

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.
    

Detailed description: 
      AvandametTM combines two oral antihyperglycemic agents, rosiglitazone maleate and metformin
      hydrochloride, with different but complementary mechanisms of action to improve glycemic
      control while reducing circulating insulin levels in patients with type 2 diabetes. AvandiaTM
      and AmarylTM combine two antidiabetic agents, rosiglitazone maleate and glimepiride.
      Glimepiride is an effective antihyperglycemic agent which has a low incidence of
      hypoglycemia, symptomatic hypoglycemia, severe hypoglycemia, and confirmed hypoglycemia.
      Subjects in this study who are inadequately controlled on diet, exercise and a submaximal
      dose of metformin or sulfonylurea (SU) will be randomized to either a combination of
      metformin plus rosiglitazone (AvandametTM) or a combination of AvandiaTM + AmarylTM or a
      Metformin monotherapy arm. As per the Canadian Diabetes Association (CDA) guidelines, their
      fasting plasma glucose and A1C to be 7 (mmol/L / percent) or less throughout the study. If
      the subject does not achieve the target then either AvandametTM or AvandiaTM and AmarylTM or
      Metformin will be up-titrated in an effort to reach this CDA recommended target. This study
      will attempt to demonstrate that the either combination arm of rosiglitazone plus metformin
      (AvandametTM) or the other combination arm of AvandiaTM + AmarylTM will provide greater
      glycemic control while avoiding the side-effects associated with the use of maximal dose
      metformin.
    

Intervention name(s): Avandamet; Avandia and Amaryl; Metformin
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 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
Other intervention name(s): rosiglitazone maleate and metformin hydrochloride; Avandamet 2 mg / 500 mg; Avandamet 4 mg / 500 mg; Avandamet 4 mg / 1000 mg; rosiglitazone maleate and glimepiride; Avandia (rosiglitazone maleate) 4 mg; Avandia (rosiglitazone maleate) 8 mg; Amaryl (glimepiride) 1 mg; Amaryl (glimepiride) 2 mg; Amaryl (glimepiride) 4 mg; Metformin 500 mg; Metformin 850 mg
Intervention MeSH terms: Metformin; Glimepiride; Rosiglitazone; Maleic acid
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment