Additional GLP-1 Analogue on CSII Treatment for Poorly Controlled Type 2 Diabetic Patients (AGAC2)

Background: Continuous subcutaneous insulin infusion (CSII) has been demonstrated to be an effective clinical tool for intensive insulin therapy in Type 1 diabetic patients. Type 2 diabetes patients have been proved to have decreased of glucagon-like peptide-1 (GLP-1) levels. Injection of GLP-1 receptor agonists are associated with improved glycemic control. Nevertheless, the clinical effects and mechanisms are still unclear when additional supplement of GLP-1 analogue in cooperation with intensive CSII treatment for poorly controlled Type 2 diabetes patients. This study is designed to understand the complementary pharmacological effects of GLP-1 analogue on intensive CSII treatment.

Methods: Sixty poorly controlled Type 2 diabetes patients will be admitted to the ward for 6 days CSII intensive treatment. Following the normalization of blood glucose at first 3 days, the patients are randomly assigned with combined therapy with exenatide injection or saline for another 3 days. The clinical assessments of insulin requirement, insulin secretion, insulin resistance glycemic excursions and cytokines will perform immediately during or after the study.

In the poorly controlled type 2 DM, insulin therapy is the treatment of choice to make sugar on target. Actually, however, the general control rate is not good and partially due to the complex etiology in type 2 DM. GLP-1 deficiency is the mostly emphasized in modern practice. In order to study the effect of GLP-1 analogue in insulinized type 2 DM patients, investigators have to optimize the insulin therapy in the first priority. Continuous subcutaneous insulin infusion (CSII) or insulin pump is a viable choice for patients with type 1 or type 2 DM who want close-to-physiologic insulin treatment. By means of the insulin pump therapy, standardized sugar control profile in type 2 DM patients could be achieved in a short time. Investigators can further evaluate the clinical response under GLP-1 analogue or not.

• Drug: Exenatide
  Exenatide 5 microgram bid sc.
  Other Name: Byetta
• Drug: Normal saline
  Normal saline 2 u bid sc.
  Other Name: Normal Saline

• Active Comparator: GLP-1
  Intervention: Drug: Exenatide
• Placebo Comparator: Normal saline
  Intervention: Drug: Normal saline

Inclusion Criteria:

• Age > 20 years old
• DM diagnosed > 2 years
• HbA1c level of 8% to 12%
• Receiving insulin premixed insulin twice daily and total insulin daily dose > 0.6 u/kg/day

Exclusion Criteria:

• Severe comorbidity, including CHF, CVA, liver cirrhosis, COPD, Cushing's syndrome etc.
• Psychologic problems, including anxiety
• Incorporation, including personal and familial factors