A Comparison of Adding Exenatide With Switching to Exenatide in Patients With Type 2 Diabetes Experiencing Inadequate Glycemic Control With Sitagliptin Plus Metformin

• Percentage of Patients Achieving HbA1c <=7.0% [ Time Frame: Baseline to 20 Weeks ] [ Designated as safety issue: No ]
  Percentage of patients whose baseline HbA1c was > 7.0% achieving HbA1c <=7.0% at endpoint (Week 20)
• Percentage of Patients Achieving HbA1c <7.0% [ Time Frame: Baseline to 20 Weeks ] [ Designated as safety issue: No ]
  Percentage of patients whose baseline HbA1c was >=7.0% achieving HbA1c <7.0% at endpoint (Week 20)
• Percentage of Patients Achieving HbA1c <=6.5% [ Time Frame: Baseline to 20 Weeks ] [ Designated as safety issue: No ]
  Percentage of patients whose baseline HbA1c was > 6.5% achieving HbA1c <=6.5% at endpoint (Week 20)
• Change in FSG (mmol/L) [ Time Frame: Baseline to 20 Weeks ] [ Designated as safety issue: No ]
  Change in fasting serum glucose (FSG) from baseline to endpoint (Week 20)
• Change in Body Weight (kg) [ Time Frame: Baseline to 20 Weeks ] [ Designated as safety issue: No ]
  Change in body weight from baseline to endpoint (Week 20)
• Change in Waist Circumference (cm) [ Time Frame: Baseline to 20 Weeks ] [ Designated as safety issue: No ]
  Change in waist circumference from baseline to endpoint (Week 20)
• Waist-to-Hip Ratio [ Time Frame: Baseline to 20 Weeks ] [ Designated as safety issue: No ]
  Change in waist-to-hip ratio from baseline to endpoint (Week20)
• SMBG (mmol/L) [ Time Frame: Baseline to 20 Weeks ] [ Designated as safety issue: No ]
  7 point Self Monitored Blood Glucose Profiles - daily mean value (Week 20)
• Change in Triglycerides (mmol/L) [ Time Frame: Baseline to 20 Weeks ] [ Designated as safety issue: No ]
  Change in triglycerides from baseline to endpoint (Week 20)
• Change in HDL (mmol/L) [ Time Frame: Baseline to 20 Weeks ] [ Designated as safety issue: No ]
  Change in high-density lipoprotein (HDL) cholesterol from baseline to endpoint (Week 20)
• Change in LDL (mmol/L) [ Time Frame: Baseline to 20 Weeks ] [ Designated as safety issue: No ]
  Change in low-density lipoprotein (LDL) cholesterol from baseline to endpoint (Week 20)
• Change in Total Cholesterol (mmol/L) [ Time Frame: Baseline to 20 Weeks ] [ Designated as safety issue: No ]
  Change in total cholesterol from baseline to endpoint (Week 20)
• Incidence of Hypoglycemia (Overall) [ Time Frame: Baseline to 20 Weeks ] [ Designated as safety issue: No ]
  Incidence of hypoglycemic episodes experienced overall during the study
• Incidence of Severe Hypoglycemia(Overall) [ Time Frame: Baseline to 20 Weeks ] [ Designated as safety issue: No ]
  Incidence of severe hypoglycemia experienced overall during the study
• Incidence of Nocturnal Hypoglycemia (Overall) [ Time Frame: Baseline to 20 Weeks ] [ Designated as safety issue: No ]
  Incidence of nocturnal hypoglycemia experienced overall during the study
• Incidence of Confirmed Hypoglycemia(Overall) [ Time Frame: Baseline to 20 Weeks ] [ Designated as safety issue: No ]
  Incidence of confirmed hypoglycemia experienced overall during the study

• To compare treatment arms in terms of proportion of patients achieving HbA1c ≤7.0%, <7.0% and ≤6.5% at endpoint [ Time Frame: 20 Weeks ] [ Designated as safety issue: No ]
• To compare treatment arms in terms of change from baseline to endpoint in fasting serum glucose [ Time Frame: 20 Weeks ] [ Designated as safety issue: No ]
• To compare treatment arms in terms of change from baseline to endpoint in body weight [ Time Frame: 20 Weeks ] [ Designated as safety issue: No ]
• To compare treatment arms in terms of change from baseline to endpoint in waist circumference and waist-to-hip ratio [ Time Frame: 20 Weeks ] [ Designated as safety issue: No ]
• To compare treatment arms in terms of 7-point self-monitored blood glucose (SMBG) profiles and mean blood glucose measurement based on 7-point SMBG [ Time Frame: 20 Weeks ] [ Designated as safety issue: No ]
• To compare treatment arms in terms of change from baseline to endpoint in serum lipids [ Time Frame: 20 Weeks ] [ Designated as safety issue: No ]
• To compare treatment arms in terms of safety and tolerability [ Time Frame: 20 Weeks ] [ Designated as safety issue: No ]

The purpose of this study is to determine whether ceasing sitagliptin and switching to exenatide and metformin is non-inferior to adding exenatide to sitagliptin and metformin, in those patients with type 2 diabetes who are experiencing inadequate glycemic control with a combination of sitagliptin and metformin.

• Drug: exenatide and sitagliptin
  exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; sitagliptin-100mg tablet orally once a day
  Other Name: exenatide-Byetta; sitagliptin-Januvia
• Drug: exenatide and placebo
  exenatide-subcutaneous injection, 5mcg (4 weeks) followed by 10mcg (16 weeks), twice a day; placebo-tablet orally once a day
  Other Name: exenatide-Byetta

• Experimental: 1
  Intervention: Drug: exenatide and sitagliptin
• Placebo Comparator: 2
  Intervention: Drug: exenatide and placebo

Inclusion Criteria:

• Present with type 2 diabetes

• Patients have been treated with a stable dose of the following for at least 3 months prior to screening:

  • 100 mg/day sitagliptin and
  • ≥1500 mg/day metformin, or maximum tolerated dose (extended release or immediate-release).
• Have inadequate glycemic control as evidenced by an HbA1c between 7.1% and 9%, inclusive.
• Have a body mass index (BMI) ≥20 kg/m2 and <45 kg/m2

Exclusion Criteria:

• Are currently enrolled in, or discontinued within the last 30 days (or longer, if local guidelines require) from, a clinical trial involving an off-label use of an investigational drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.
• Have previously completed or withdrawn from this study or any other study investigating exenatide.
• Have a known allergy or hypersensitivity to exenatide, sitagliptin or excipients contained in exenatide or sitagliptin.
• Used drugs for weight loss (for example, orlistat, sibutramine, phenylpropanolamine, or similar over-the-counter medications) within 1 month of screening.

• Are currently treated with any of the following excluded medications:

  • Thiazolidinediones (TZD) within 3 months of screening.
  • Sulfonylurea (SU) within 3 months of screening.
  • Dipeptidyl peptidase-4 [DPP-4] inhibitors, with the exception of sitagliptin, within 3 months of screening.
  • Meglitinide derivatives (for example, repaglinide or nateglinide) within 3 months of screening.
  • Alpha-glucosidase inhibitors (for example, miglitol or acarbose) within 3 months of screening.
  • Exogenous insulin within the 3 months prior to screening.
  • Drugs that directly affect gastrointestinal motility, including, but not limited to: metoclopramide, cisapride, and chronic macrolide antibiotics.
  • Systemic corticosteroids (excluding topical and inhaled preparations) by oral, intravenous (IV), or intramuscular (IM) route used regularly (for longer than 1 month) or used within 1 month immediately prior to screening.
  • Any other oral antidiabetic (OAD) agent, other than sitagliptin or metformin, within 3 months prior to screening.