Efficacy of Alogliptin With Pioglitazone (Actos®) in Subjects With Type 2 Diabetes Mellitus
Condition: Diabetes Mellitus
MeSH terms: Diabetes Mellitus
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of this study is to evaluate the combination of alogliptin, once daily (QD), and
      pioglitazone in patients with type 2 diabetes mellitus who are inadequately controlled with
      diet and exercise alone.
    

Detailed description: 
      There are approximately 19 million people in the United States who have been diagnosed with
      diabetes mellitus, of which 90% to 95% is type 2. The prevalence of type 2 diabetes varies
      among racial and ethnic populations and has been shown to correlate with age, obesity, family
      history, history of gestational diabetes, and physical inactivity. Over the next decade, a
      marked increase in the number of adults with diabetes mellitus is expected, placing an
      ever-increasing burden on families and the health care system.

      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 reaching
      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.

      As the rate of newly diagnosed cases of type 2 diabetes mellitus continues to grow, so does
      the need for products that will provide better glycemic control and improved safety and
      tolerability. Alogliptin and pioglitazone have complementary actions. Alogliptin inhibits the
      degradation of glucagon-like peptide-1 by inhibiting the enzyme dipeptidyl peptidase IV, thus
      augmenting glucose-dependent insulin secretion while pioglitazone is a peripheral and hepatic
      insulin sensitizer. Given the complementary mechanisms of action of alogliptin (stimulates
      insulin secretion) and pioglitazone (enhances insulin sensitivity), the addition of
      combination therapy in treatment naïve type 2 diabetes patients may potentially allow the
      patients to reach and maintain their glycosylated hemoglobin goal more effectively.

      The aim of this study is to evaluate the effectiveness of the combination of alogliptin with
      pioglitazone in patients who are inadequately controlled on diet and exercise alone. Study
      participation is anticipated to be approximately 8.5 months.
    

Intervention name(s): Alogliptin; Pioglitazone; Placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Alogliptin tablets.; Pioglitazone tablets.; Matching placebo tablets.
Other intervention name(s): SYR-322; Actos; AD4833
Intervention MeSH terms: Pioglitazone; Alogliptin
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