Effect on Beta Cell Function and Glycaemic Control After Insulin and Exenatide Sequential Therapy

Study Overview
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Brief Summary
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Whether GLP-1 receptor agonists sequential therapy in newly diagnosed type 2 diabetic patients can further improve glycemic control, diabetes remission rate and β-cell function after the short-term insulin intensive therapy.

Detailed Description
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The UK Prospective Diabetes Study has shown that β-cell function progressively deteriorates over time in people with type 2 diabetes mellitus,irrespective of lifestyle and existing pharmacological interventions. 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 has been proved improving beta-cell function and usually leading to a temporary remission time,but the remission rate in a year is only about 50%. The effect of GLP-1 receptor agonists on beta-cells is stimulation of glucose-dependent insulin release, followed by enhancement of insulin biosynthesis. It is stimulating beta-cell proliferation, induction of islet neogenesis, and inhibition of ß-cell apoptosis. Exenatide is an GLP-1 receptor agonist. Exenatide exerts direct effects on β-cell, which indicates that may contribute to delay disease progression. However, no study has evaluated effect of short-term intensive insulin sequential exenatide therapy model on β-cell function and glycemic remission rate in newly diagnosed type 2 diabetic patients. Our hypotheses is whether GLP-1 receptor agonists sequential therapy in newly diagnosed type 2 diabetic patients can further improve glycemic control, diabetes remission rate and β-cell function after the short-term insulin intensive therapy.

Official Title
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Effect of Short-term Intensive Insulin Sequential Exenatide Therapy on Beta Cell Function and Glycaemic Control in Patients With Newly Diagnosed Type 2 Diabetes :a Multicenter Prospective Randomized Control Study

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Exenatide
* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: newly diagnosed type 2 diabetes without drug treatment 25-70 years old age Fasting glucose between 7.0-16.7mmol / L BMI at 20   35 kg/m2 and stable for at least 3 month(weight fluctuations within three months does not exceed 10%) females who have no plan of pregnancy during the study Exclusion Criteria: acute or chronic complications of diabetes myocardial infarction or cerebrovascular events within three months serious gastrointestinal diseases other serious concomitant diseases liver or kidney dysfunction:Transaminase (ALT and AST) greater than 3 times the upper limit of the normal range or creatinine levels greater than 133μmol / L GAD antibodies positive history of pancreatitis or pancreatic cancer; pregnant or breastfeeding women. severe hypertension (blood pressure> 180/110mmhg) using corticosteroids, immunosuppressants and cytotoxic therapy.

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 70 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<br>patients were all received a short-term intensive insulin therapy,then randomised to Exenatide group(10 ug two times a day for three months) | Drug: Exenatide<br>* Exenatide (10 ug/bid for 3 months)<br>* Other names: GLP-1 receptor agonist;|
| Active Comparator: Metformin<br>patients were all received a short-term intensive insulin therapy,then randomised to metformin group(850mg two times a day for three months) | Drug: Metformin<br>* Metformin 850 mg/bid for 3 months<br>* Other names: Glucophage;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| time to glycaemic remission | time of glycaemic remission at 1 year after exenatide sequential therapy followed by a short-term insulin intensive treatment | up to 1 year | 
| remission rate of type 2 diabetes at a year. | remission rate of type 2 diabetes after short-term intensive insulin and exenatide sequencial therapy | up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the beta cell function change | the beta cell function change expressed by the ratio of proinsulin to insulin in fasting state and HOMA beta,the ratio of Glucose change to insulin change between at 30min and 0min time point of OGTT | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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the newly onset type 2 diabetes, short-term insulin treatment, exenatide sequential therapy, beta cell function, glycaemic remission