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

Summary: 
      The purpose of this study is to evaluate the safety and efficacy of alogliptin, once daily
      (QD), taken in combination with pioglitazone in adults with type 2 diabetes mellitus.
    

Detailed description: 
      Over the past 30 years, the prevalence of diabetes has increased dramatically throughout the
      world due to population growth, aging, urbanization, increasing obesity, and physical
      inactivity. The total number of people with type 2 diabetes mellitus is projected to rise
      from 171 million in 2000 to 366 million in 2030. The incidence of type 2 diabetes mellitus in
      the United States alone is expected to increase from approximately 17 to 30.3 million by the
      year 2030. Type 2 diabetes mellitus is associated with a number of long-term microvascular
      and macrovascular complications associated with a reduced quality of life and increased
      morbidity and mortality. It is anticipated that the increasing incidence of type 2 diabetes
      mellitus will place an ever-increasing burden on families, increase national expenditures for
      health care services, and decrease worker productivity.

      Current pharmacologic interventions for type 2 diabetes mellitus include a diverse range of
      antidiabetic medications with different mechanisms of action including insulin and insulin
      analogues, sulfonylureas, metformin, meglitinides, thiazolidinediones, inhibitors of
      alpha-glucosidase, analogs of glucagon-like peptide-1 and synthetic analogues of human
      amylin. Despite the variety of medications, many have clinically important or potentially
      life-threatening side effects, restricted use in many subpopulations, concerns with long-term
      tolerability, and challenges related to compliance due to side effects and route of
      administration. All of these reasons contribute to the difficulties patients have achieving
      the target glycosylated hemoglobin level less than 7%.

      SYR-322 (alogliptin) is a selective, orally available inhibitor of the dipeptidyl peptidase-4
      enzyme. Dipeptidyl peptidase-4 enzyme is thought to be primarily responsible for the in vivo
      degradation of 2 peptide hormones released in response to nutrient ingestion, namely
      glucagon-like peptide-1 and glucose-dependent insulinotropic peptide. Both peptides exert
      important effects on islet beta cells to stimulate glucose-dependent insulin secretion as
      well as regulating beta cell proliferation and cytoprotection. Glucagon-like peptide-1, but
      not glucose-dependent insulinotropic peptide, inhibits gastric emptying, glucagon secretion,
      and food intake. Glucose-dependent insulinotropic peptide has been shown to enhance insulin
      secretion by direct interaction with a glucose-dependent insulinotropic peptide -specific
      receptor on islet beta cells. The glucose-lowering actions of glucagon-like peptide-1, but
      not glucose-dependent insulinotropic peptide, are preserved in patients with type 2 diabetes
      mellitus.

      Pioglitazone (ACTOS®) is a thiazolidinedione developed by Takeda Chemical Industries, Ltd.
      (Osaka, Japan) that is approved for the treatment of type 2 diabetes mellitus. Pioglitazone
      is a selective peroxisome proliferator-activated receptor-gamma agonist that decreases
      insulin resistance in the periphery and liver resulting in increased insulin-dependent
      glucose disposal and decreased hepatic glucose output.

      Given the complementary mechanisms of action of alogliptin (stimulation of insulin secretion)
      and pioglitazone (enhancement of insulin sensitivity), the goal of this study is to evaluate
      the efficacy of the combination of alogliptin with pioglitazone in patients who are
      inadequately controlled on metformin. Study participation is anticipated to be approximately
      7 months.
    

Intervention name(s): Alogliptin; Alogliptin placebo; Pioglitazone; Pioglitazone placebo
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Alogliptin tablets.; Alogliptin placebo-matching tablets.; Pioglitazone tablets.; Pioglitazone placebo-matching tablets.
Other intervention name(s): SYR-322; ACTOS®
Intervention MeSH terms: Pioglitazone; Alogliptin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Diabetes Mellitus, Type 2; Drug Therapy; Diabetes Mellitus, Non Insulin Dependent; Glucose Intolerance; Hyperglycemia