Research of Exenatide for Overweight/Obese PCOS Patients With IGR

Study Overview
=================
Brief Summary
-----------------
Compare the therapeutic effects of exenatide, metformin and their combination for 3 months on reproductive and metabolic improvements of overweight/obese PCOS patients with impaired glucose regulation.

Detailed Description
-----------------
The investigators designed a randomized control trial to compare the therapeutic effects of exenatide, metformin and their combination for 3 months on reproductive and metabolic improvements of overweight/obese PCOS patients with impaired glucose regulation. The investigators plan to enroll 183 patients. Inclusion criteria: 1) Patients who have PCOS which is diagnosed according to 2003 Rotterdam criteria; 2) Overweight / obesity diagnostic criteria is based on WHO-WPR; 3) IGR diagnostic criteria is based on 1999 WHO diagnostic criteria; 4) have been treated with dietary and behavioral intervention for 3 months but are ineffective; 5) have no use of other hypoglycemic drugs before 3 months of treatment. Patients with serious complications (cardiovascular events and recent significant liver, kidney or lung disease within 3 months); high blood pressure (>160/100mmHg); active infection; secondary diabetes; pregnancy; alcohol abuse; allergic to GLP-1 receptor agonist or metformin are excluded. Then the investigators plan to randomly divide the 183 patients into 3 groups: exenatide group, metformin group, and combination group, with 61 samples for each group. Each group use specific treatment (showed as the group name) for 3 months. Before and after the intervention, the blood samples would be collected to detect blood glucose, insulin, lipid profile, sex hormones, blood chemistry for liver and kidney function, hsCRP etc., as well as the anthropometric measurement and image examinations. All patients discontinue after 12 weeks of treatment and only routine lifestyle intervention is performed after that. All patients receive 75 g OGTT test and insulin releasing test again 12 weeks after drug withdrawal to observe the IGR remission rate. To accurately assess the insulin secretion of islet β-cell, 13 patients would be randomly selected from MET group and from EX group respectively to receive the two-step hyperglycemic clamp before the intervention and after 12-week treatment. The investigators will compare the data and finally identify the treatment effect of exenatide on PCOS patients.

Official Title
-----------------
Research of Exenatide for Management of Reproductive and Metabolic Dysfunction in Overweight/Obese PCOS Patients With Impaired Glucose Regulation

Conditions
-----------------
Overweight and Obesity, Disorder of Glucose Regulation, Polycystic Ovary Syndrome

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: have PCOS which is diagnosed according to 2003 Rotterdam criteria; overweight / obesity diagnostic criteria is based on WHO-WPR ; IGR diagnostic criteria is based on 1999 WHO diagnostic criteria; have been treated with dietary and behavioral intervention for 3 months but are ineffective; have no use of other hypoglycemic drugs before 3 months of treatment. Exclusion Criteria: Except for serious complications (cardiovascular events and recent significant liver, kidney or lung disease within 3 months) high blood pressure (>160/100mmHg) active infection secondary diabetes pregnancy alcohol abuse allergic to GLP-1 receptor agonist or metformin

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
Female

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 |
| --- | --- |
| Experimental: Exenatide<br>Drug: Byetta Generic name: Exenatide Dosage form: 5ug and 10ug Dosage: 10-20ug/day Frequency: twice a day Duration: 3 months | Drug: Exenatide<br>* Use Exenatide for 3 months to treat PCOS<br>* Other names: Byetta;|
| Active Comparator: Metformin<br>Drug: Glucophage Generic name: Metformin Dosage form: 500mg Dosage: 1500-2000mg/day Frequency: 500mg three times a day/1000mg twice a day Duration: 3 months | Drug: Metformin<br>* Use Metformin for 3 months to treat PCOS<br>* Other names: Glucophage;|
| Experimental: Combination<br>Drug: Byetta and Glucophage Generic name: Exenatide Dosage form: Exenatide 5ug and 10ug; Metformin 500mg Dosage: Exenatide10-20ug/day; Metformin 1500-2000mg/day Frequency: Exenatide twice a day; Metformin 500mg three times a day/1000mg twice a day Duration: 3 months | Drug: Exenatide<br>* Use Exenatide for 3 months to treat PCOS<br>* Other names: Byetta;Drug: Metformin<br>* Use Metformin for 3 months to treat PCOS<br>* Other names: Glucophage;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of intravenous blood glucose from impaired glucose regulation to normal glucose regulation | To compare the intravenous blood glucose of three groups 12 weeks after withdrawal. All patients discontinue after 12 weeks of treatment and only routine lifestyle intervention is performed after that. All patients receive 75 g OGTT test and insulin releasing test again 12 weeks after drug withdrawal to observe the IGR remission rate. To accurately assess the insulin secretion of islet β-cell, 13 patients would be randomly selected from MET group and from EX group respectively to receive the two-step hyperglycemic clamp before the intervention and after 12-week treatment. Remission rate = Number of patients who has normal glucose tolerance 12 weeks after withdrawal / Number of patients who completed treatments × 100% | up to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of hyperandrogenism | To compare the free androgen index (FAI =total serum testosterone x 100 / Sex Hormone Binding Globulin) of three groups after 12-week treatment | up to 12 weeks | 
| Improvement of blood lipid | To compare the circulating lipid level(triglyceride, total cholesterol, HDL-C, LDL-C, etc.) of three groups after 12-week treatment | up to 12 weeks | 
| Improvement of fatty liver | To compare the number of fatty liver patients diagnosed by ultrasonography of three groups after 12-week treatment | up to 12 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Polycystic Ovary Syndrome, Overweight and Obesity, Impaired Glucose Regulation, Exenatide, Metformin