Efficacy of Pioglitazone and Glimepiride Combination Therapy in Treating Subjects With Type 2 Diabetes Mellitus.
Condition: Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of this study is to determine the effect of pioglitazone, once daily (QD), and
      glimepiride combination therapy compared to glimepiride monotherapy in subjects with Type 2
      Diabetes.
    

Detailed description: 
      Tight glycemic control is mandatory for the prevention and treatment of vascular
      complications in patients suffering from diabetes mellitus. After onset of Type 2 Diabetes,
      patients are usually treated with diet along with or without different combinations of oral
      drugs. One first-line drug class are sulfonylurea drugs that are preferably provided to
      patients who are not obese. The mode of action of sulfonylurea drugs is to increase beta-cell
      secretion, but it could be shown that they lead to deterioration of the beta-cell secretion
      product over time, resulting in increased proinsulin secretion. Since proinsulin is an
      independent cardiovascular risk factor, recent publications have demonstrated an increased
      risk for cardiovascular events in patients treated with sulfonylurea drugs as compared to
      other treatment methods.

      Combination therapy of sulfonylurea drugs with glitazones has been shown to counterbalance
      the effect of deteriorated beta-cell secretion and to improve insulin sensitivity and the
      levels of proinsulin, C-peptide and other laboratory surrogate markers for cardiovascular
      risk. Proving that the treatment of diabetic patients with higher doses of beta cytotropic
      agents can be avoided and beta-cell function can be preserved by using pioglitazone in
      combination with low dose sulfonylurea drugs, it will be possible to optimize the treatment
      of patients with type 2 diabetes who are not controlled efficiently by sulfonylurea drugs
      monotherapy.

      In this study patients will be enrolled who are inefficiently treated with a Glimepiride
      monotherapy. Patients will be either randomized to a combinational therapy of Pioglitazone
      and Glimepiride or Glimepiride monotherapy. If possible, study medication will be up-titrated
      to maximal dosage levels in both treatment arms to observe maximal and comparable treatment
      effects. Stable effects on beta-cell function will be observed after 24 weeks of treatment.
    

Intervention name(s): Pioglitazone and Glimepiride; Glimepiride
Intervention type(s): Drug; Drug
Intervention description(s): Pioglitazone 30 mg, tablets, orally, once daily and Glimepiride 2 mg, tablets, orally once daily for two weeks; increased to:
Pioglitazone 30 mg, tablets, orally, once daily and Glimepiride 4 mg, tablets, orally, once daily for two weeks; increased to:
Pioglitazone 45 mg, tablets, orally, once daily and Glimepiride 4 mg, orally, once daily for up to 20 weeks.; Pioglitazone placebo-matching tablets, orally, once daily and Glimepiride 4 mg, tablets, orally once daily for two weeks; increased to:
Pioglitazone placebo-matching tablets, orally, once daily and Glimepiride 5 mg, tablets, orally once daily for two weeks; increased to:
Pioglitazone placebo-matching tablets, orally, once daily and Glimepiride 6 mg, tablets, orally once daily for up to 20 weeks.
Other intervention name(s): ACTOS®
Intervention MeSH terms: Pioglitazone; Glimepiride
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Glucose Metabolism Disorder; Dysmetabolic Syndrome; Type II Diabetes; Diabetes Mellitus, Lipoatrophic; Dyslipidemia; Drug Therapy