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

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

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 Overview

• Status: Unknown
• Conditions: Polycystic Ovary Syndrome
• Intervention / Treatment: Drug: Metformin; Drug: Exenatide 2 MG

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Yan Deng; Phone Number: 13167559763; Email: yanndeng@163.com
• Study Contact Backup: Name: Aiju Sun

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 1000730
      • Recruiting
      • Peking Union Medical College Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Metformin; 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; 500 mg tid for 12 weeks; Other Names: Glucophage
Experimental: Metformin+EQW; 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; 500 mg tid for 12 weeks; Other Names: Glucophage; Drug: Exenatide 2 MG; Exenatide injection once weekly for 12 weeks; Other Names: Bydureon

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital

Publications and helpful links

General Publications

• Ma RL, Deng Y, Wang YF, Zhu SY, Ding XS, Sun AJ. Short-term combined treatment with exenatide and metformin for overweight/obese women with polycystic ovary syndrome. Chin Med J (Engl). 2021 Nov 3;134(23):2882-2889. doi: 10.1097/CM9.0000000000001712.

Study record dates

Study Major Dates

• Study Start (Anticipated): July 20, 2019
• Primary Completion (Anticipated): February 28, 2020
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: July 8, 2019
• First Submitted That Met QC Criteria: July 21, 2019
• First Posted (Actual): July 23, 2019

Study Record Updates

• Last Update Posted (Actual): July 23, 2019
• Last Update Submitted That Met QC Criteria: July 21, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: GLP-1; PCOS; Metformin; exenatide; glucagon-like peptide 1; GLP-1RA; glucagon-like peptide 1 receptor agonist
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Endocrine System Diseases; Disease; Ovarian Cysts; Cysts; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Body Weight; Polycystic Ovary Syndrome; Syndrome; Overweight; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Obesity Agents; Incretins; Metformin; Exenatide
• Other Study ID Numbers: PCOS201907

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No