Metformin vs Metformin Combined With GLP-1RA (Glucagon-like Peptide 1 Receptor Agonist) on Overweight/Obese PCOS Patients

Study Overview
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Brief Summary
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The purpose of this study was to determine whether metformin combined with exenatide once weekly (EQW) is more effective than metformin alone in the treatment of overweight/obese women with polycystic ovary syndrome (PCOS). Background therapies were Diane-35 or/and progesterone capsule. 80 participants were randomized to use either metformin or metformin+EQW for 12 weeks. Greater changes in body weight were anticipated in patients treated with EQW+metformin than metformin alone in those treated with metformin.

Official Title
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Study on the Effect of Metformin vs Metformin Combined With GLP-1 RA (Exenatide) on Overweight/Obese Patients With Polycystic Ovary Syndrome (PCOS)

Conditions
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Polycystic Ovary Syndrome

Intervention / Treatment
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* Drug: Metformin
* Drug: Exenatide 2 MG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females 18 years to 40 years of age Diagnosed as PCOS by the 2003 Rotterdam criteria. Overweight/obesity (BMI≥25 kg/m2) No pregnant plan in recent 6 months Written consent for participation in the study Exclusion Criteria: type 1 or type 2 diabetes mellitus Subjects have other endocrine diseases, such as adrenal hyperplasias or tumor, androgen-secreting tumors, Cushing's syndrome, thyroid diseases, and hyperprolactinemia Diagnosed with or have a family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) Serious systemic disease or malignant tumor History of pancreatitis (chronic, acute or recurrent) Body weight change ≥10% at 3 months before treatment Used oral contraceptives or sex hormone drugs in the past 1 month Used oral glucocorticoids in the past 1 month Substance (alcohol or drug) abuse or dependence within 3 months; Heavy smokers (smokers who smoke 20 or more cigarettes a day) or heavy drinkers (>10g/d) Subjects have a severe systemic disease, such as cardiovascular system Renal impairment, eGFR<60ml/min/1.73m2 Increase of transaminases up to < 2.5 times of upper limit of normal value Have a history of thromboembolic disease or thrombotic tendency Subjects in pregnant or lactating or within 1 year after delivery. Subjects have an allergic history to the drugs used in the study Subjects have participated in other clinical researches of medicine within 1 month prior to randomization. Use of metformin, glucagon-like peptide -1 receptor agonists, or weight loss medications (prescription or OTC) within 30 days before screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

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 |
| --- | --- |
| Active Comparator: Metformin<br>Background therapy: Diane-35 one pill by mouth, once daily, beginning on Day 5 of the menstrual cycle for 21 consecutive days followed by a 7-day interval without medication; for three cycles (3 months) Metformin: Metformin was initiated at a dose of 250mg q.d. and increased by 250mg up to 500 mg t.i.d. | Drug: Metformin<br>* 500 mg tid for 12 weeks<br>* Other names: Glucophage;|
| Experimental: Metformin+EQW<br>Background therapy: Diane-35 one pill by mouth, once daily, beginning on Day 5 of the menstrual cycle for 21 consecutive days followed by a 7-day interval without medication; for three cycles (3 months) Metformin: Metformin was initiated at a dose of 250mg q.d. and increased by 250mg up to 500 mg t.i.d. EQW: Participants will receive long-acting Exenatide once a week for 12 weeks | Drug: Metformin<br>* 500 mg tid for 12 weeks<br>* Other names: Glucophage;Drug: Exenatide 2 MG<br>* Exenatide injection once weekly for 12 weeks<br>* Other names: Bydureon;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in body weight |  | Patient's body weight was measured at the baseline and after 12 weeks of clinical trial | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects who lost ≥5% of their body weight |  | 12 weeks | 
| Proportion of subjects who lost ≥ 10% of their body weight |  | 12 weeks | 
| Change in body mass index (BMI) |  | 12 weeks | 
| Change in waist circumference(WC) |  | 12 weeks | 
| Change in hip circumference (HC) |  | 12 weeks | 
| Changes in lipid accumulation product(LAP) | LAP=(WC(cm)-58)×TG (mmol/L) | 12 weeks | 
| Changes in Visceral obesity index(VAI) | VAI = (WC(cm)/39.68+(1.88×BMI))×(TG (mmol/l)/1.03)×(1.31/HDL (mmol/l)) | 12 weeks | 
| Changes in blood pressure |  | 12 weeks | 
| Changes in Blood Glucose and Insulin During the oral glucose tolerance test (OGTT) | glucose obtained at 0,30,60 and 120 minutes during the OGTT. HOMA-IR=Glu0(mmol/l)×Ins0(mU/ml)/22.5 Matsuda index=1000/ square(Ins0 (mU/ml) ×Glu0 (mmol/l)×mean Glu(mmol/l)×meanIns(mU/ml)] QUICKI= 1/Log[Glu0 (mU/ml) ×Ins0 (mmol/l)] HOMA-β=20×Ins0 (mU/ml) /(Glu0 (mmol/l)-3.5) MBCI= Ins0 (mU/ml)×Glu0(mmol/l)／(Glu120(mmol/l)＋Glu60 (mmol/l)-2×Glu0 (mmol/l)） ΔI30/ΔG30 = (Ins30- Ins0)/( Glu30- Glu0) | 12 weeks | 
| Changes in total cholesterol (TC) |  | 12 weeks | 
| Changes in serum triglyceride (TG) |  | 12 weeks | 
| Changes in high-density lipoproteincholesterol (HDL-C) |  | 12 weeks | 
| Changes in low-density lipoproteincholesterol (LDL-C) |  | 12 weeks | 
| Changes in lipoprotein(a) |  | 12 weeks | 
| Changes in apolipoprotein a1(ApoA1) |  | 12 weeks | 
| Changes in apolipoprotein B(ApoB) |  | 12 weeks | 
| Changes in free fatty acid (FFA) |  | 12 weeks | 
| Changes in high sensitivity C reactive protein(hsCRP) |  | 12 weeks | 
| Frequency of menstrual cycle | The number of menstrual cycles during the previous year was recorded and the menstrual cycle ratio calculated by dividing 12 by the number of menstrual cycles in the previous year . During the study period, the patients in a menstrual diary recorded vaginal bleeding over 12 weeks. The effects of treatment intervention on menstrual cycle interval was calculated evaluated by dividing 3 by the number of menstrual cycles recorded in each patient's menstrual cycle diary. | 12 weeks | 
| Changes in testosterone |  | 12 weeks | 
| Changes in Dehydroepiandrosterone sulfate (DHEAS) |  | 12 weeks | 
| Changes in Luteinizing Hormone (LH) |  | 12 weeks | 
| Changes in follicle stimulating hormone(FSH) |  | 12 weeks | 
| Changes in LH/FSH |  | 12 weeks | 
| Changes in Acne severity score | This system divides the face, chest, and upper back into 6 areas: the forehead, right cheek,left cheek, nose, chin, and torso (chest and upper back combined). Each acne lesion is described and scored as a comedo (1 point), papule (2 points), pustule (3 points), or nodule (4 points); absence of an acne lesion in an area results in a score of 0 points. The local score for each anatomic area is determined by multiplying the score of the most severe lesion by an area factor (1 to 3), and the local scores of the 6 areas are then added together to obtain the total score. Acne severity is graded as none (total score, 0 points), mild (total score, 1-18 points), moderate (total score, 19-30 points), severe (total score, 31-38 points), and very severe (total score N38 points) | 12 weeks | 
| Changes in ovarian volume |  | 12 weeks | 
| Changes in follicular number of 2-9mm in diameter |  | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PCOS, GLP-1, GLP-1RA, exenatide, Metformin, glucagon-like peptide 1, glucagon-like peptide 1 receptor agonist