Exeantide in Type 2 Diabetes on Insulin

• weight [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  To compare the body weight at the end of 12 weeks in patients on exenatide subcutaneously twice daily (5 or 10 mcg/injection) as compared to controls in insulin treated obese type 2 diabetic patients
• HbA1c [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  To compare the HbA1c at the end of 12 weeks in patients on exenatide subcutaneously twice daily (5 or 10 mcg/injection) as compared to controls in insulin treated obese type 2 diabetic patients.
• inflammation [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  To investigate the hypothesis that a single dose of exenatide subcutaneously (5 mcg/injection) decreases the intranuclear NFκB binding activity and decreases the transcription of pro-inflammatory genes regulated by NFκB in MNC's of insulin treated type 2 diabetic patients as compared to placebo.

Exenatide has been shown to result in better glycemic control in type II diabetes patients. Obesity and diabetes are states of increased inflammation; exenatide is expected to lead to decreased inflammation by virtue of better glycemic control and weight loss.

The purpose of this study is to determine if the addition of Exenatide to diabetic patients will reduce the requirements of insulin particularly the short acting insulin. Exenatide may also lead to decreased inflammation by virtue of better glycemic control and weight loss, or an independent effect.

• Drug: exenatide 5 mcg
  exenatide 5 mcg
• Drug: exenatide 10 mcg
  exenatide 10 mcg
• Drug: placebo
  saline sq

• Experimental: exenatide 5 mcg
  exenatide 5 mcg
  Intervention: Drug: exenatide 5 mcg
• Experimental: exenatide 10 mcg
  exenatide 10 mcg
  Intervention: Drug: exenatide 10 mcg
• Placebo Comparator: placebo
  placebo
  Intervention: Drug: placebo

Inclusion Criteria:

• Males or females 20-75 years of age inclusive.
• Type 2 diabetes
• On insulin therapy
• HbA1c ≥7.5% and ≤ 9%
• BMI ≥ 30 kg/m2
• Subjects on statins, ACE inhibitors, metformin, thiazolidinediones and antioxidants will be allowed as long as they are on stable doses of these compounds and the dosage in not changed during the study.

Exclusion Criteria:

• Coronary event or procedure (myocardial infarction, unstable angina, coronary artery bypass, surgery or coronary angioplasty) in the previous four weeks
• Pregnancy
• Hepatic disease (abnormal LFT's)
• Use of DPP4 inhibitors.
• Renal impairment (serum creatinine > 1.5)
• Participation in any other concurrent clinical trial
• Any other life-threatening, non-cardiac disease
• Uncontrolled hypertension (BP > 160/100 mm of Hg)
• Congestive Heart Failure.
• Use of an investigational agent or therapeutic regimen within 30 days of study