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

Peking Union Medical College Hospital80 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Polycystic Ovary Syndrome

Interventions

Metformin

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 40 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Change in body weight

Time frame: Patient's body weight was measured at the baseline and after 12 weeks of clinical trial

Secondary Outcomes

Proportion of subjects who lost ≥5% of their body weight

Time frame: 12 weeks

Proportion of subjects who lost ≥ 10% of their body weight

Time frame: 12 weeks

Change in body mass index (BMI)

Time frame: 12 weeks

Change in waist circumference(WC)

Time frame: 12 weeks

Change in hip circumference (HC)

Time frame: 12 weeks

Changes in lipid accumulation product(LAP)

LAP=(WC(cm)-58)×TG (mmol/L)

Time frame: 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))

Time frame: 12 weeks

Changes in blood pressure

Time frame: 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)

Time frame: 12 weeks

Changes in total cholesterol (TC)

Time frame: 12 weeks

Changes in serum triglyceride (TG)

Time frame: 12 weeks

Changes in high-density lipoproteincholesterol (HDL-C)

Time frame: 12 weeks

Changes in low-density lipoproteincholesterol (LDL-C)

Time frame: 12 weeks

Changes in lipoprotein(a)

Time frame: 12 weeks

Changes in apolipoprotein a1(ApoA1)

Time frame: 12 weeks

Changes in apolipoprotein B(ApoB)

Time frame: 12 weeks

Changes in free fatty acid (FFA)

Time frame: 12 weeks

Changes in high sensitivity C reactive protein(hsCRP)

Time frame: 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.

Time frame: 12 weeks

Changes in testosterone

Time frame: 12 weeks

Changes in Dehydroepiandrosterone sulfate (DHEAS)

Time frame: 12 weeks

Changes in Luteinizing Hormone (LH)

Time frame: 12 weeks

Changes in follicle stimulating hormone(FSH)

Time frame: 12 weeks

Changes in LH/FSH

Time frame: 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)

Time frame: 12 weeks

Changes in ovarian volume

Time frame: 12 weeks

Changes in follicular number of 2-9mm in diameter

Time frame: 12 weeks

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts