A Study of the Effect of Glucagon-like Peptide 1(GLP-1) Receptor Agonist in Combination With Metformin Therapy on Diabetes Remission in Subjects With Newly Diagnosed Type 2 Diabetes Who Are Overweight or Obese

Study Overview
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Brief Summary
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The purpose of this study is to determine the effect of GLP-1 receptor agonist on inducing diabetes remission in newly diagnosed type 2 diabetes who are overweight or obese

Detailed Description
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Most of type 2 diabetes are characterized by being overweight or obese mainly caused by insulin resistance. GLP-1 receptor agonist has been proved to help to lose weight and improve insulin resistance. In this study, we suppose that GLP-1 receptor agonist has the effect of inducing diabetes remission in newly diagnosed type 2 diabetes who are overweight or obese and has its advantages

Official Title
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A Randomized,Active-controlled,Open-label Clinical Trial to Evaluate the Effect of GLP-1 Receptor Agonist (Exenatide Injection) in Combination With Metformin Therapy Compared to Premixed Insulin (BIAsp30) in Combination With Metformin Therapy on Diabetes Remission in Subjects With Newly Diagnosed Type 2 Diabetes Who Are Overweight or Obese

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Exenatide
* Drug: BIAsp30
* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A signed and dated informed consent form obtained from the subject before any study related procedures take place. Age ≥18 years to ≤65 years at Visit 1. The subject has a new diagnosis of type 2 diabetes without any treatment. HbA1c ≥8.0% to ≤14.0% at Visit 1. BMI(Body Mass Index)≥24kg/m2 to ≤40kg/m2 at Visit 1. Exclusion Criteria: The subject has a history of type 1 diabetes or a secondary form of diabetes. The subject has received an anti-diabetic drug before the screening visit. Treatment with systemic steroids 2 months prior to screening Treatment with anti-obesity drug 2 months prior to screening or any other treatment at the time of screening(i.e. surgery etc) leading to unstable body weight. The subject has a history of acute or chronic pancreatitis Any gastrointestinal diseases or surgeries that induce chronic malabsorption Cancer and medical history of cancer(except basal cell skin cancer or squamous cell skin cancer). The subject has a history of recurrent severe hypoglycaemia. Cardiovascular disease,within the last 6months prior to screening,defined as: stroke;decompensated heart failure New York Heart Association(NYHA) class III or IV;Myocardial infarction;unstable angina pectoris;or coronary bypass graft or angioplasty. Uncontrolled treated/untreated severe hypertension (systolic blood pressure ≥180 millimetre(mm) mercury(Hg) and/or diastolic blood pressure ≥100 millimetre(mm) mercury(Hg). Impaired liver function,defined as alanine aminotransferase(ALT) or aspartate aminotransferase(AST) ≥2.5 times upper limit of normal. Impaired renal function,defined as serum-creatinine ≥125umol/l for males and ≥110umol/l for females. Females who are pregnant or breast-feeding, males and females of childbearing potential,who do not agree to prevent conception during the study. Known or suspected abuse of alcohol,narcotics or illicit drugs.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exenatide and Metformin<br>Exenatide in Combination With Metformin | Drug: Exenatide<br>* subcutaneous injection，5ug twice a day the first month，10ug twice a day the second and third month<br>Drug: Metformin<br>* oral，0.85g，twice a day in three months<br>|
| Active Comparator: BIAsp30 and Metformin<br>BIAsp30 in Combination With Metformin | Drug: BIAsp30<br>* subcutaneous injection，fit dosage twice a day in three months<br>Drug: Metformin<br>* oral，0.85g，twice a day in three months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Inducing Diabetes Remission |  | At the end of 12-week treatment | 
| Change of Rate of Maintaining Diabetes Remission |  | 3,6,12,24,36 months after 12-week treatment | 
| Time of Maintaining Diabetes Remission |  | up to 36 months after 12-week treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Blood Pressure |  | Baseline and 0,3,6,12,24,36 months after 12-week treatment | 
| Change of Heart Rate |  | baseline and 0,3,6,12,24,36 months after 12-week treatment | 
| Change of Weight |  | baseline and 0,3,6,12,24,36 months after 12-week treatment | 
| Change of Waistline |  | baseline and 0,3,6,12,24,36 months after 12-week treatment | 
| Change of Glycosylated Hemoglobin |  | baseline and 0,3,6,12,24,36 months after 12-week treatment | 
| Change of Pancreatic Beta-cell Function | Pancreatic Beta-cell Function will be evaluated by insulin releasing test. The fasting and 2-hour postprandial plasma glucose concentrations and serum insulin concentrations will be tested. | baseline and 0,3,6,12,24,36 months after 12-week treatment | 
| Change of Insulin Resistance Index |  | baseline and 0,3,6,12,24,36 months after 12-week treatment | 
| The Incidence of Hypoglycemia |  | During the 12-week treatment | 
| The Incidence of Diabetic Retinopathy |  | up to 36 months after 12-week treatment | 
| The Incidence of Diabetic Nephropathy |  | up to 36 months after 12-week treatment |