Efficacy and Safety of SYR-472 in Subjects With Type 2 Diabetes Mellitus
Condition: Diabetes Mellitus
MeSH terms: Diabetes Mellitus
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to determine the efficacy and safety of SYR-472, once daily
      (QD), in subjects with type 2 diabetes mellitus who have not achieved glycemic control with
      diet and exercise, or by taking metformin.
    

Detailed description: 
      Type 2 diabetes mellitus is a complex metabolic disorder characterized by abnormal insulin
      secretion and glucose homeostasis, resulting from impaired pancreatic beta-cell function and
      insulin resistance in target tissues. The worldwide prevalence of type 2 diabetes mellitus is
      reaching epidemic proportions, and the total number of cases is expected to reach 221 million
      by 2010. The high incidence of the disease and its associated complications places a
      significant burden on healthcare systems.

      The primary risk factor for the development of type 2 diabetes mellitus is obesity and its
      associated insulin resistance. Insulin resistance is characterized by an impaired response to
      the physiologic effects of insulin and leads to decreased cellular glucose uptake, increased
      hepatic gluconeogenesis, and a compensatory increase in insulin secretion that contributes to
      beta-cell exhaustion. Therefore in the insulin-resistant state, blood glucose and insulin
      levels are increased. The relationship between improved glycemic control in patients with
      type 2 diabetes mellitus and the delay or prevention of comorbidities has been reported in
      the Diabetes Control and Complications Trial and the United Kingdom Prospective Diabetes
      Study. Therefore, reduction of persistent hyperglycemia is the highest priority in treating
      this disease.

      Diet and exercise are important and effective measures for maintaining glycemic control in
      individuals with insulin resistance, impaired glucose tolerance, and type 2 diabetes
      mellitus, particularly in the early stages of disease progression. In cases where diet and
      exercise alone fail to adequately maintain glycemic control, oral antidiabetic drugs are
      typically used. Combination oral therapy and eventually insulin are usually required to
      maintain lower blood glucose levels but can result in adverse effects including hypoglycemia
      and weight gain. Therefore, novel safe and effective antidiabetic therapies are needed.

      Dipeptidyl peptidase-4 is a ubiquitous aminopeptidase that is widely expressed in many
      tissues; it is thought to be primarily responsible for the in vivo degradation of at least
      two gut-derived incretin hormones, namely glucagon-like peptide-1 and glucose-dependent
      insulinotropic peptide, which are both released in response to nutrient ingestion.
      Glucagon-like peptide-1 has been demonstrated to augment glucose-dependent insulin secretion;
      suppress glucagon release and hepatic gluconeogenesis; inhibit gastric emptying, and reduce
      appetite and food intake. Glucagon-like peptide-1 and glucose-dependent insulinotropic
      peptide also have been shown to promote insulin biosynthesis and stimulate beta cell
      proliferation and survival. Orally available inhibitors of dipeptidyl peptidase-4 activity
      have been developed that increase intact postprandial glucagon-like peptide-1 levels after
      oral administration.

      SYR-472 is a selective inhibitor of dipeptidyl peptidase-4 in development to improve glycemic
      control in patients with type 2 diabetes mellitus. The aim of this study is to evaluate
      SYR-472 in subjects with type 2 diabetes mellitus who have not previously achieved adequate
      glycemic control with lifestyle modification (diet/exercise) or metformin antidiabetic
      monotherapy. Study participation is anticipated to be up to 20 weeks.
    

Intervention name(s): SYR-472; SYR-472; SYR-472; SYR-472; Placebo; Sitagliptin
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): SYR-472 3.125 mg, tablets, orally, once daily with lifestyle modification and/or metformin stable dose therapy for up to 12 weeks.; SYR-472 12.5 mg, tablets, orally, once daily with lifestyle modification and/or metformin stable dose therapy for up to 12 weeks.; SYR-472 50 mg, tablets, orally, once daily with lifestyle modification and/or metformin stable dose therapy for up to 12 weeks.; SYR-472 100 mg, tablets, orally, once daily with lifestyle modification and/or metformin stable dose therapy for up to 12 weeks.; SYR-472 placebo-matching tablets, orally, once daily with lifestyle modification and/or metformin therapy for up to 12 weeks.; Sitagliptin 100 mg, tablets, orally, once daily with lifestyle modification and/or metformin stable dose therapy for up to 12 weeks.
Other intervention name(s): Januvia™
Intervention MeSH terms: Sitagliptin Phosphate
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