Effect of Different Interventions on Glycemic Control and β-cell Function in Newly Diagnosed Type 2 Diabetic Patients

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to investigate and evaluate the effects of different interventions (1. exenatide, 2. insulin, 3. thiazolidinedione) on glycemic control and β-cell function in newly diagnosed drug-naïve type 2 diabetic patients.

Detailed Description
-----------------
One of the fundamental defects in type 2 diabetes mellitus is declining β-cell function. Exenatide targets multiple metabolic disturbances in type 2 diabetes and exerts direct effects on β-cell, which indicates that it may not only contribute to the glucose control but also delay disease progression. There are trials demonstrated efficacy, safety and tolerability of exenatide. However, no study has compared the effects of exenatide with other hypoglycemic therapies with β cell protective function in newly diagnosed and drug-naïve type 2 diabetic patients. This current study is thus designed to evaluate the effects of exenatide, insulin and pioglitazone on glycemic control and β-cell function in newly diagnosed drug-naïve type 2 diabetic patients.

Official Title
-----------------
Comparison of Exenatide, Insulin or Pioglitazone on Glycaemic Control and β-cell Function in Drug-naïve Type 2 Diabetic Patients: A Multicentre Randomized Parallel-group Trial

Conditions
-----------------
Diabetes Mellitus, Type 2, Newly Diagnosed

Intervention / Treatment
-----------------
* Drug: exenatide injection
* Drug: Mixed Protamine Zinc Recombinant Human Insulin Lispro 25R
* Drug: Pioglitazone


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: newly-diagnosed type 2 diabetic patients, drug naïve age 30 70 years HbA1c 7.0 10.0% BMI 20 35 kg/m2, stable body weight (≤10% variation) for at least 3 months prior to screening female patients of reproductive age should practice a reliable method of birth control throughout the study Exclusion Criteria: acute or severe chronic diabetic complications congestive heart failure (NYHA grade Ⅲ Ⅳ) severe gastrointestinal disease severe osteoporosis or history of pathological fracture,or use of bisphosphonates preparation other severe intercurrent illness serum aminotransferase (ALT and AST) level higher than 2 times of the upper normal limits and/or serum creatinie≥133µmol/L (1.5mg/dL) tested positive for glutamic acid decarboxylase antibody use of weight loss drugs, corticosteroids, drugs known to affect gastrointestinal motility, transplantation medications, or any investigational drug history of pancreatitis serum triglyceride ≥ 5.0 mmol/L pregnancy

Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Exenatide<br> | Drug: exenatide injection<br>* Patients in exenatide group will be treated with exenatide (Byetta®, Eli Lilly and Company) 5 µg BID for the first 4 weeks and then 10 µg BID thereafter.<br>* Other names: Byetta®(Eli Lilly and Company);|
| Active Comparator: Premixed insulin analog<br> | Drug: Mixed Protamine Zinc Recombinant Human Insulin Lispro 25R<br>* Patients in insulin group will be treated with premixed insulin analog (Humalog Mix 25, Eli Lilly and Company). The initial insulin doses are 0.4 IU/kg per day(50% before breakfast and 50% before dinner). Insulin doses are titrated following a forced schedule according to blood glucose before breakfast and dinner.<br>* Other names: Humalog Mix 25®（Eli Lilly and Company);|
| Active Comparator: pioglitazone<br> | Drug: Pioglitazone<br>* Patients in thiazolidinedione group will be treated with Pioglitazone 30mg daily as single dose. The dose will be increased to 45mg daily after 4 weeks.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the Comparison Between Treatment Groups of the Changes From Baseline in HbA1c at 48 Weeks |  | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Achieving HbA1c <7% and ≤ 6.5% and Effect of Different Interventions on Fasting and Postprandial Plasma Glucose Concentration, Blood Pressure, Lipid Profiles |  | 48 weeks | 
| β-cell Function (Acute Insulin Response During IVGTT; HOMA-B, Disposition Index and Proinsulin/Insulin Ratio) |  | 48 weeks | 
| Safety and Tolerability in Different Groups |  | 48 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
exenatide, newly diagnosed, diabetes mellitus, type 2, premixed insulin analog, thiazolidinedione, β-cell function, glycemic control