Efficacy and Safety of Exenatide in Japanese Patients With Type 2 Diabetes Who Are Treated With Oral Antidiabetic(s)

• Percentage of Patients Achieving HbA1c < 7.0% [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Percentage of subjects whose HbA1c was >=7.0% at baseline who achieved an HbA1c < 7.0% at endpoint (i.e., number of eligible subjects who achieved HbA1c < 7.0% divided by total number of eligible subjects times 100)
• Percentage of Patients Achieving HbA1c < 6.5% [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Percentage of subjects whose HbA1c was >=6.5% at baseline who achieved an HbA1c < 6.5% at endpoint (i.e., number of eligible subjects who achieved HbA1c < 6.5% divided by total number of eligible subjects times 100)
• Change in Fasting Blood Glucose [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Change in fasting blood glucose from baseline to endpoint (i.e., fasting blood glucose at week 24 minus fasting blood glucose at week 0)
• Change in Body Weight [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Change in body weight form baseline to endpoint (i.e., body weight at week 24 minus body weight at week 0)
• Change in Total Cholesterol [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Change in total cholesterol from baseline to endpoint (i.e., total cholesterol at week 24 minus total cholesterol at week 0)
• Change in Low Density Lipoprotein Cholesterol (LDL-C) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Change in LDL-C from baseline to endpoint (i.e., LDL-C at week 24 minus LDL-C at week 0)
• Change in High Density Lipoprotein Cholesterol (HDL-C) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Change in HDL-C from baseline to endpoint (i.e., HDL-C at week 24 minus HDL-C at week 0)
• Change in Triglycerides [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Change in triglycerides from baseline to endpoint (i.e., triglycerides at week 24 minus triglycerides at week 0)
• Change in Waist Size [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Change in waist size from baseline to endpoint (i.e., waist size at week 24 minus waist size at week 0)
• Change in Waist-to-hip Ratio [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Change in waist-to-hip ratio from baseline to endpoint (i.e., waist-to-hip ratio at week 24 minus waist-to-hip ratio at week 0). Waist-to-hip ratio is waist circumference divided by hip circumference.
• 7 Point Self-monitored Blood Glucose (SMBG) Profiles [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Self-monitored blood glucose at 7 different time points during the day (glucose measurements before and 2 hours after the start of the morning, midday, and evening meals, and at bedtime).
• Change in Homeostatis Model Assessment - Beta Cell Function (HOMA-B) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Change in HOMA-B from baseline to endpoint (i.e., HOMA-B at week 24 minus HOMA-B at week 0). HOMA-B is a measurement of beta cell function.
• Change in Homeostatis Model Assessment - Insulin Resistance (HOMA-R) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Change in HOMA-R from baseline to endpoint (i.e., HOMA-R at week 24 minus HOMA-R at week 0). HOMA-R is a measurement of insulin resistance.
• Change in Serum Insulin [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Change in serum insulin from baseline to endpoint (i.e., serum insulin at week 24 minus serum insulin at week 0)
• Change in C-peptide [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Change in C-peptide from baseline to endpoint (i.e., C-peptide at week 24 minus C-peptide at week 0)
• Change in 1,5-anhydroglucitol [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Change in 1,5-anhydroglucitol from baseline to endpoint (i.e., 1,5-anhydroglucitol at week 24 minus 1,5-anhydroglucitol at week 0)

• To assess the effect of exenatide on the following measures of efficacy: *Proportion of patients achieving HbA1c <7.0% and <6.5%; *Glucose (fasting); *Body weight; *Serum lipids; *Waist size and waist/hip ratio. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
• To assess the effect of exenatide on the following measures of efficacy: *Glucose measured at different times throughout the day; *Beta cell function and insulin sensitivity as assessed by homeostasis model assessment analyses and C-peptide. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
• To assess the effect of exenatide on the following measures of safety: *Treatment emergent adverse events; *Laboratory tests; *Vital signs; *Electrocardiogram; *Anti-exenatide antibody; *Hypoglycemia. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
• To measure the effect of exenatide on glycemic control (HbA1c) over an extended period of time. [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]

This long term, placebo-controlled trial is intended to assess the efficacy and safety of exenatide, dosed twice a day, in Japanese patients with Type 2 Diabetes who are treated with oral antidiabetic(s) but not well controlled.

• Drug: exenatide
  subcutaneous injection, 5mcg, twice a day
  Other Names:

  • LY2148568
  • Byetta
• Drug: exenatide
  subcutaneous injection, 10mcg, twice a day
  Other Names:

  • LY2148568
  • Byetta
• Drug: placebo
  subcutaneous injection, volume equivalent to 5mcg or 10mcg exenatide, twice a day

• Experimental: 1
  Intervention: Drug: exenatide
• Experimental: 2
  Intervention: Drug: exenatide
• Placebo Comparator: 3
  Intervention: Drug: placebo

Inclusion Criteria:

• Diagnosed with type 2 diabetes.
• Has been treated by sulfonylurea (SU) alone, SU and biguanide, or SU and thiazolidinedione for at least 90 days prior to study start. In a patient receiving SU alone, the dose must be within the dose range from maximum maintenance dose to maximum approved dose. The patients with concomitant use of alpha glucosidase inhibitors (acarbose, voglibose or miglitol) or meglitinide derivatives (mitiglinide or nateglinide) can be included in this study, but these drugs must be discontinued at study start.
• Have HbA1c 7.0% to 10% at study start.
• Have a body weight >=50 kg.

Exclusion Criteria:

• Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.
• Have participated in this study previously or any other study using exenatide or GLP-1 analogs within the last 90 days.
• Have been treated with any exogenous insulin within 90 days before study start.
• Have been continuously treated with any drug that directly affects gastrointestinal motility for more than a total of 21 days in the 90 days prior to study start.
• The combination therapy of sulfonylurea, biguanide and thiazolidinedione is not allowed.