The Effect of GLP-1 Agonists Versus OCs on Reproductive Disorders and Cardiovascular Risks in Overweight PCOS

NCT03151005 | Completed Phase 4 Results FDA Drug

• 1 other identifier: Xinqiao Endocrinology
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

Polycystic ovary syndrome (PCOS) is a health problem that affects one in 10 women of childbearing age, which is usually characterized by hormonal imbalance and metabolism problems such as hyperandrogenism and obesity. Diane 35 pills are classified as oral contraceptives, which effectively reduces circulating androgens and are treatment for hyperandrogenism caused androgenic skin symptoms and irregular menstrual cycles. GLP-1 Receptor Agonist(e.g. exenatide, liraglutide) have the effects of lowering blood sugar and weight control by inhibiting of gastric emptying and reducing food intake. This study aims to evaluate the effect of metformin-GLP-1 Receptor agonist combination versus metformin-Diane-35 combination treatment on lipid metabolism and cardiovascular risks in overweight polycystic ovarian syndrome (PCOS) patients.

Conditions

Polycystic Ovary Syndrome (PCOS); Overweight; Obesity

Keywords

Polycystic Ovary Syndrome (PCOS); Overweight; Obesity; GLP-1 Agonist; Oral contraceptives (OCs); Metformin; Reproductive Disorders; Cardiovascular risk factor; Lipid Metabolism

Outcome Measures

Primary Outcomes (1)

• Assessment of Reproductive Functions

  Concentration of LH was measured in mIU/ml.

  12 weeks

Secondary Outcomes (4)

• Basic Vital Signs

  12 weeks

• Assessment of Liver Function

  12 weeks

• Assessment of Blood Pressure

  12 weeks

• Assessment of Reproductive Function

  12 weeks

Study Arms (2)

Metformin-GLP-1 Receptor Agonist

EXPERIMENTAL

Metformin-GLP-1 Receptor Agonist Therapy: metformin 0.5 g/time by mouth, 3 times per day, with 5 ug exenatide subcutaneous injection twice per day, for 4 weeks, then change to 10ug exenatide subcutaneous injection twice per day for 8 weeks; or metformin 0.5 g/time by mouth, 3 times per day, with 0.6mg liraglutide subcutaneous injection once per day, for 1 weeks, then change to 1.2-1.8 mg liraglutide subcutaneous injection according to patient's blood glucose condition, twice per day for 8 weeks.

Drug: Metformin-GLP-1 Receptor Agonist

Metformin-Oral Contraceptive(OC)

ACTIVE COMPARATOR

Metformin-Oral Contraceptive(OC) Therapy: metformin 0.5 g/ time by mouth, 3 times per day, with Diane 35(OC) 1 piece per day by mouth, for 12 weeks.

Drug: Metformin-Oral Contraceptive(OC)

Interventions

Metformin-GLP-1 Receptor Agonist DRUG

metformin oral with exenatide/liraglutide subcutaneous injection.

Also known as: Metformin-exenatide/liraglutide Therapy

Metformin-GLP-1 Receptor Agonist

Metformin-Oral Contraceptive(OC) DRUG

metformin with Diane 35 oral intake.

Also known as: Metformin, Diane 35

Metformin-Oral Contraceptive(OC)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Participants had no concurrent illness and were not on any prescription or over-the-counter medication that was likely to affect insulin sensitivity or lipids for the preceding 12 weeks.
• Participants were advised not to change physical activity or dietary habits during the study period. All subjects were overweight/obese \[body mass index (BMI) \>=24 kg/m2 or waistline\>=85cm \].
• All subjects had normal thyroid-stimulating hormone and prolactin levels.

You may not qualify if:

• smoking, alcohol use, or having taken medication within 2 months of the study that is known to affect reproductive or metabolic functions.
• age below 18 yr or over 50 yr.
• postmenopausal.
• uncontrolled hypertension (blood pressure \>=160/100 mm Hg).
• preexisting OPs or GLP-1 agonists supplementation
• alcohol intake greater than 20 g/d, or pregnancy.
• signs of liver or renal failure or active liver disease (ALT \> 2.5× the upper limit of normal values).
• PLT\<60\*10\^9/L,Hb\<100g/L, smoking, alcohol use.
• The patient that cannot complete the intervention or have other conditions that is not appropriate to enter the group, such as patients who are taking glucocorticoid steroids or malignant tumor treatment, etc.

Sponsors & Collaborators

• Xinqiao Hospital of Chongqing: lead

Study Sites (1)

The Second Affiliated Hospital, Third Military Medical University

Chongqing, Chongqing Municipality, 400037, China

Location

Related Publications (12)

• Macut D, Bjekic-Macut J, Rahelic D, Doknic M. Insulin and the polycystic ovary syndrome. Diabetes Res Clin Pract. 2017 Aug;130:163-170. doi: 10.1016/j.diabres.2017.06.011. Epub 2017 Jun 12.

  PMID: 28646699 RESULT

• Zhou BF; Cooperative Meta-Analysis Group of the Working Group on Obesity in China. Predictive values of body mass index and waist circumference for risk factors of certain related diseases in Chinese adults--study on optimal cut-off points of body mass index and waist circumference in Chinese adults. Biomed Environ Sci. 2002 Mar;15(1):83-96.

  PMID: 12046553 RESULT

• Barthelmess EK, Naz RK. Polycystic ovary syndrome: current status and future perspective. Front Biosci (Elite Ed). 2014 Jan 1;6(1):104-19. doi: 10.2741/e695.

  PMID: 24389146 RESULT

• Dumesic DA, Oberfield SE, Stener-Victorin E, Marshall JC, Laven JS, Legro RS. Scientific Statement on the Diagnostic Criteria, Epidemiology, Pathophysiology, and Molecular Genetics of Polycystic Ovary Syndrome. Endocr Rev. 2015 Oct;36(5):487-525. doi: 10.1210/er.2015-1018.

  PMID: 26426951 RESULT

• Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004 Jan;19(1):41-7. doi: 10.1093/humrep/deh098.

  PMID: 14688154 RESULT

• Yildiz BO, Bozdag G, Yapici Z, Esinler I, Yarali H. Prevalence, phenotype and cardiometabolic risk of polycystic ovary syndrome under different diagnostic criteria. Hum Reprod. 2012 Oct;27(10):3067-73. doi: 10.1093/humrep/des232. Epub 2012 Jul 9.

  PMID: 22777527 RESULT

• Farrell K, Antoni MH. Insulin resistance, obesity, inflammation, and depression in polycystic ovary syndrome: biobehavioral mechanisms and interventions. Fertil Steril. 2010 Oct;94(5):1565-74. doi: 10.1016/j.fertnstert.2010.03.081. Epub 2010 May 14.

  PMID: 20471009 RESULT

• Escobar-Morreale HF. Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment. Nat Rev Endocrinol. 2018 May;14(5):270-284. doi: 10.1038/nrendo.2018.24. Epub 2018 Mar 23.

  PMID: 29569621 RESULT

• Ruan X, Kubba A, Aguilar A, Mueck AO. Use of cyproterone acetate/ethinylestradiol in polycystic ovary syndrome: rationale and practical aspects. Eur J Contracept Reprod Health Care. 2017 Jun;22(3):183-190. doi: 10.1080/13625187.2017.1317735. Epub 2017 May 2.

  PMID: 28463030 RESULT

• Wang YW, He SJ, Feng X, Cheng J, Luo YT, Tian L, Huang Q. Metformin: a review of its potential indications. Drug Des Devel Ther. 2017 Aug 22;11:2421-2429. doi: 10.2147/DDDT.S141675. eCollection 2017.

  PMID: 28860713 RESULT

• Jiang Y, Wang Z, Ma B, Fan L, Yi N, Lu B, Wang Q, Liu R. GLP-1 Improves Adipocyte Insulin Sensitivity Following Induction of Endoplasmic Reticulum Stress. Front Pharmacol. 2018 Oct 16;9:1168. doi: 10.3389/fphar.2018.01168. eCollection 2018.

  PMID: 30459598 RESULT

• Liao M, Li X, Zhang H, Zhou L, Shi L, Li W, Shen R, Peng G, Zhao H, Shao J, Wang X, Sun Z, Zheng H, Long M. Effects and plasma proteomic analysis of GLP-1RA versus CPA/EE, in combination with metformin, on overweight PCOS women: a randomized controlled trial. Endocrine. 2024 Jan;83(1):227-241. doi: 10.1007/s12020-023-03487-4. Epub 2023 Aug 31.

  PMID: 37653215 DERIVED

MeSH Terms

Conditions

Polycystic Ovary Syndrome; Overweight; Obesity

Interventions

Metformin; Cyproterone

Condition Hierarchy (Ancestors)

Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Chlorinated

Limitations and Caveats

Limitations of this trial include a relatively small sample size and single-center design.

Results Point of Contact

• Title: Min Long, MD
• Organization: Department of Endocrinology, Xinqiao Hospital, Army Military Medical University

longmin_casper@163.com

023-68763255

Study Officials

• Min long, MD

  Department of Endocrinology, Xinqiao Hospital,Third Military Medical University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Deputy Chief Physician, Associated professor

Study Record Dates

• First Submitted: April 28, 2017
• First Posted: May 12, 2017
• Study Start: July 1, 2017
• Primary Completion: April 1, 2021
• Study Completion: April 23, 2021
• Last Updated: December 4, 2023
• Results First Posted: December 4, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Data will be avaliable within 6 months of study completion.
• Access Criteria: Data access requests will be reviewed by an external independent review panel. Requestors will be required to sign a data access agreement.

Locations

CN (1)