Efficacy of Pioglitazone on Macrovascular Outcome in Patients With Type 2 Diabetes
Condition: Diabetes Mellitus
MeSH terms: Diabetes Mellitus
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of this study is to determine whether pioglitazone, once daily (QD), can delay
      the time to death, heart attack, acute coronary syndrome, heart bypass surgery, stroke, leg
      bypass surgery or amputation in patients with type 2 diabetes.
    

Detailed description: 
      Diabetes mellitus is one of the most common non-communicable diseases worldwide. More than 22
      million persons have been diagnosed with diabetes in the European region of the International
      Diabetes Federation. Complications of diabetes involving both microvascular and macrovascular
      systems contribute to increased disability and reduced life expectancy. Damage to the
      coronary, cerebral (brain), and peripheral vascular beds as a consequence of diabetes is
      responsible for the increased macrovascular illness and death associated with the disease.

      Insulin resistance is common to the genesis of both atherosclerosis and type 2 diabetes
      mellitus. In diabetes, insulin resistance is coupled to receptor dysfunction. In
      atherosclerosis, insulin resistance may have both direct effects on the cardiovascular system
      as well as indirect effects provoked by imbalances in blood glucose, lipids, clotting
      factors, endothelial function, and other factors. Considerable indirect evidence suggests
      that peroxisome proliferator-activated receptor agonists may favorably influence
      macrovascular outcome, either through modification of risk factors (such as blood lipids) or
      through effects on the vessel wall.

      Pioglitazone, a thiazolidinedione compound discovered by Takeda Pharmaceutical Company, Ltd,
      functions as a peroxisome proliferator-activated receptor agonist as its mode of action.

      This study is designed to assess whether pioglitazone in combination with other medications
      administered for glycemic management of type 2 diabetes might reduce the incidence of
      macrovascular events associated with this disease compared with placebo. Individuals who
      participate in this study will provide written informed consent and will be required to
      commit to screening and randomization visits and approximately 17 additional visits (1 every
      2 months for the first year and every 3 months thereafter) at the study center. Study
      participation is anticipated to be about 40 months (or approximately 3 years and 4 months).
      Multiple procedures will occur at each visit which may include fasting, blood collection,
      physical examinations and electrocardiograms.
    

Intervention name(s): Pioglitazone; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Pioglitazone 15 mg to 45 mg, tablets, orally, once daily for up to 48 months.; Pioglitazone placebo-matching tablets, orally, once daily for up to 48 months
Other intervention name(s): Actos; AD4833
Intervention MeSH terms: Pioglitazone
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