Clinical trial NCT03352869: Research of Exenatide for Overweight/Obese PCOS Patients With IGR
Official title: Research of Exenatide for Management of Reproductive and Metabolic Dysfunction in Overweight/Obese PCOS Patients With Impaired Glucose Regulation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Polycystic Ovary Syndrome
Overweight and Obesity
Disorder of Glucose Regulation
Keywords: Polycystic Ovary Syndrome
Overweight and Obesity
Impaired Glucose Regulation
Exenatide
Metformin
Lead sponsor: RenJi Hospital
Sponsor class: OTHER
First posted: 2017-11-24
Enrollment: 183
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. 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.

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

Primary outcomes:
measure: Improvement of intravenous blood glucose from impaired glucose regulation to normal glucose regulation
timeFrame: up to 12 weeks
Secondary outcomes:
measure: Improvement of hyperandrogenism
timeFrame: up to 12 weeks
measure: Improvement of blood lipid
timeFrame: up to 12 weeks
measure: Improvement of fatty liver
timeFrame: up to 12 weeks
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Renji Hospital Department of Endocrinology and Metabolism
Study officials:
affiliation: RenJi Hospital Department of Endocrinology and Metabolism
name: Tao Tao, MD
role: STUDY_CHAIR
References:
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citation: Jensterle Sever M, Kocjan T, Pfeifer M, Kravos NA, Janez A. Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin. Eur J Endocrinol. 2014 Feb 7;170(3):451-9. doi: 10.1530/EJE-13-0797. Print 2014 Mar.
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citation: Jensterle M, Kravos NA, Goricar K, Janez A. Short-term effectiveness of low dose liraglutide in combination with metformin versus high dose liraglutide alone in treatment of obese PCOS: randomized trial. BMC Endocr Disord. 2017 Jan 31;17(1):5. doi: 10.1186/s12902-017-0155-9.
citation: Tao T, Zhang Y, Zhu YC, Fu JR, Wang YY, Cai J, Ma JY, Xu Y, Gao YN, Sun Y, Fan W, Liu W. Exenatide, Metformin, or Both for Prediabetes in PCOS: A Randomized, Open-label, Parallel-group Controlled Study. J Clin Endocrinol Metab. 2021 Mar 8;106(3):e1420-e1432. doi: 10.1210/clinem/dgaa692.