Safety Study of Pioglitazone Compared To Glyburide on Liver Function
Condition: Diabetes Mellitus; Liver
MeSH terms: Diabetes Mellitus
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of this study is to determine the liver safety of pioglitazone, once daily (QD),
      versus glyburide taken with metformin and insulin.
    

Detailed description: 
      Type 2 diabetes generally arises from an initial state of insulin resistance that coincides
      with a gradual decline in insulin secretion due to beta-cell dysfunction. Together, these
      factors contribute to impaired glucose tolerance and eventually hyperglycemia.

      Thiazolidinediones are selective agonists for the nuclear receptor peroxisomal
      proliferator-activated receptor gamma. These receptors are found in tissues with insulin
      action including adipose tissue, skeletal muscle and the liver. Thiazolidinediones reduce
      insulin resistance by enhancing insulin sensitivity in adipose tissue, muscle cells and
      hepatic cells without directly affecting insulin secretion. These effects improve glycemic
      control and result in reduced levels of circulating insulin.

      Pioglitazone is a thiazolidinedione developed by Takeda Chemical Industries, Ltd., and
      depends on the presence of insulin for its mechanism of action. Glyburide is an oral
      antidiabetic agent of the sulfonylurea class, and impacts glycemic control by stimulating the
      pancreas to release insulin, an effect that is dependent upon beta-cells in the pancreatic
      islets.

      Elevated levels of hepatic enzymes, hepatocellular inflammation, and viral susceptibility are
      known to occur with increased frequency in individuals with type 2 diabetes mellitus
      regardless of the type of antidiabetic therapy used. Subject to the approval of pioglitazone,
      the Food and Drug Administration requested a 3-year outcome study evaluating the occurrence
      of serious liver disease in subjects treated with pioglitazone. The present study was
      designed to fulfill this phase 4, postmarketing commitment to the Food and Drug
      Administration, pursuant to demonstrating the long-term hepatic safety of pioglitazone. This
      study was designed to determine whether pioglitazone is associated with a difference in the
      incidence of elevated levels of alanine aminotransferase, a marker of hepatocellular
      inflammation or injury, when compared with glyburide. Glyburide is used for treatment of
      patients with type 2 diabetes mellitus; its use in this study as a comparator should provide
      a basis for evaluating whether pioglitazone is associated with an increased risk of
      hepatocellular inflammation or injury.
    

Intervention name(s): Pioglitazone; Glyburide
Intervention type(s): Drug; Drug
Intervention description(s): Pioglitazone 15 mg or 30 mg titrated to 45 mg, tablets, orally, once daily and glyburide placebo-matching capsules, orally, once daily for up to 156 weeks.; Pioglitazone placebo-matching tablets, orally, once daily and glyburide 5 mg or 10 mg titrated to 15 mg, capsules, orally, once daily for up to 156 weeks.
Other intervention name(s): Actos; AD-4833
Intervention MeSH terms: Pioglitazone; Glyburide
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; Liver; Drug Therapy