The Effects of Short-Term Exenatide Therapy in Newly Diagnosed Type 2 Diabetic Patients
The Effects of Short-Term Exenatide Therapy in Newly Diagnosed Type 2 Diabetic Patients
Whether GLP-1 and GLP-1 receptor agonists will produce a sustained improvement in beta-cell
 function following short-term therapy is currently not known. This randomized, controlled
 trial is carried to assess the efficacy of short-term insulin therapy (NPH injection twice
 daily) compared with GLP-1 analogue (Exenatide injection twice daily) on glycemic control,
 remission rate, ß-cell function, and long-term glycemic control in newly diagnosed type 2
 diabetic patients with moderate hyperglycemia.
Background: There is a progressive deterioration in beta-cell function in type 2 diabetics,
 and it was estimated that islet function was about 50% of normal at the time of diagnosis.
 The progressive nature of type 2 diabetes is one of the major challenges in the treatment of
 affected patients, and agents that could alter the natural history of this condition would
 add greatly to current treatment approaches. Short-term intensive insulin therapy of newly
 diagnosed type 2 diabetes will improve beta-cell function and usually leading to a temporary
 remission time. The acute effect of GLP-1 and GLP-1 receptor agonists on beta-cells is
 stimulation of glucose-dependent insulin release, followed by enhancement of insulin
 biosynthesis and stimulation of insulin gene transcription. The chronic action is stimulating
 beta-cell proliferation, induction of islet neogenesis, and inhibition of ß-cell apoptosis,
 thus promoting expansion of beta-cell mass, as observed in rodent diabetes and in cultured
 beta-cells.

 Objectives: Whether GLP-1 and GLP-1 receptor agonists will produce a sustained improvement in
 beta-cell function following short-term therapy is currently not known. This randomized,
 controlled trial is carried to assess the efficacy of short-term insulin therapy (NPH
 injection twice daily) compared with GLP-1 analogue (Exenatide injection twice daily) on
 glycemic control, remission rate, beta-cell function, and long-term glycemic control in newly
 diagnosed type 2 diabetic patients with moderate hyperglycemia.

 Study Designs and Methods: We will recruit 80 newly diagnosed type 2 diabetic patients with
 moderate hyperglycemia, and another 80 newly diagnosed type 2 diabetic patients with severe
 hyperglycemia who receive intensive insulin therapy for 10-14 days, and will be randomized to
 be treated with exenatide or insulin injections. They will visit our clinics every 2 weeks in
 the first 2 visits and then every 4 weeks for 20 weeks. After the 24 weeks of intervention,
 all patients will be treated with life style modification only and follow fasting plasma
 glucose every month. Hyperglycemia relapse is defined as fasting plasma glucose more than 126
 mg/dL and confirmed two weeks later. Patients with hyperglycemia relapse will be treated with
 metformin (from 500 mg per day to 1500 mg per day)and then gliclazide-MR will be added to as
 the second step for the remaining study period. A1C measurement will be performed at
 baseline, 3, 6, 12 and 18 months, and OGTT will be performed at screen and after 6 months of
 randomization. All of these subjects were continually followed-up in our clinics for 5 years
 to evaluate their long-term glycemic control. The monotherapy failure is defined as A1C >7.0%
 with metformin 1500 mg/day.

 The primary outcomes at one year are the time of glycemic remission and remission rate at one
 year after short-term therapy. The primary outcomes at 5 years are monotherapy failure time
 and monotherapy failure rate at 5 years after short-term therapy. The secondary outcomes are
 the beta-cell function and insulin sensitivity calculated from OGTT, the comparison of A1C
 change, the proportion of subjects who reached the treatment target (A1C <7.0% or <6.5% at 1
 and 5 years). These subjects will be followed up for 5 years to evaluate their long-term
 glycemic control.

 Expected Results: We will expect to screen 100 patients, randomize 80 patients and there will
 be at least 30 patients in each group complete the one year follow-up. We expected that
 short-term intensive treated with both insulin and exenatide can get better glycemic control
 accompanied with improving the beta-cell function in newly diagnosed type 2 diabetes. We can
 compare the remission rate at one year after different short-term therapy. We will further
 evaluate the effects on the beta-cell function and long-term glycemic control. This study
 also can assess what readily available parameter would predict which patients will achieve
 long-term successful glycemic control after correction of glucose toxicity.
Inclusion Criteria:

 1. Newly diagnosed type 2 diabetic patients.

 2. Age between 30 and 70 years old.

 3. HbA1C between 7 and 9% in OPD patients

 4. If HbA1c >9.0% of blood glucose >300 mg/dL, intensive insulin therapy for 10-14 days

 Exclusion Criteria:

 1. Previous treated with anti-diabetic medication

 2. Pregnant or lactation women.

 3. Impaired liver function (ALT > 100 U/L)

 4. Impaired renal function (Serum creatinine >2.0 mg/dL)

 5. Recently suffered from MI or CVA.

 6. Patients are acute intercurrent illness.

 7. 2-hour C-peptide level < 2.0 ng/mL.

 8. History of severe hypersensitivity to any product components.

 9. History or high risk of acute pancreatitis.

 10. Now use warfarin.