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

Obesity Clinical Trial

Official title:

Randomized Clinical Trial to Evaluate The Effect of Metformin-GLP-1 Receptor Agonist Versus Oral Contraceptive (OC) Therapy on Reproductive Disorders and Cardiovascular Risks in Overweight Polycystic Ovarian Syndrome (PCOS) Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03151005
• Other study ID #: Xinqiao Endocrinology
• Status: Completed
• Phase: Phase 4
• Start date: July 1, 2017
• Est. completion date: April 23, 2021

Study information

• Verified date: November 2023
• Source: Xinqiao Hospital of Chongqing
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Groups: Experimental treatment: Metformin-GLP-1 Receptor Agonist Therapy. Regular treatment: Metformin-Oral Contraceptive(OC) Therapy. Time Point: Initial treatment; Post-treatment (4w); Post-treatment (8w); Post-treatment (12w); Assess reproductive functions and cardiovascular risk factors.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: April 23, 2021
• Est. primary completion date: April 1, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• Clinical diagnosis of PCOS according to the Rotterdam criteria based on the presence of two of three criteria: oligomenorrhoea, clinical or biochemical hyperandrogenism and polycystic ovaries on ultrasound after exclusion of other endocrine causes of hyperandrogenism.
• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Obesity
• Overweight
• Polycystic Ovary Syndrome
• Polycystic Ovary Syndrome (PCOS)
• Syndrome

Intervention

Drug:
• Metformin-GLP-1 Receptor Agonist
metformin oral with exenatide/liraglutide subcutaneous injection.
• Metformin-Oral Contraceptive(OC)
metformin with Diane 35 oral intake.

Locations

Country	Name	City	State
China	The Second Affiliated Hospital, Third Military Medical University	Chongqing	Chongqing

Sponsors (1)

Lead Sponsor	Collaborator
Xinqiao Hospital of Chongqing

Country where clinical trial is conducted

China, 

References & Publications (11)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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 — View Citation

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. — View Citation

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. — View Citation

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 in — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of Reproductive Functions	Concentration of LH was measured in mIU/ml.	12 weeks
Secondary	Basic Vital Signs	Weight and height will be combined to report BMI in kg/m^2.	12 weeks
Secondary	Assessment of Liver Function	Alanine transaminase was measured in IU/L.	12 weeks
Secondary	Assessment of Blood Pressure	Systolic blood pressure was measured in mmHg.	12 weeks
Secondary	Assessment of Reproductive Function	Changes in testosterone levels were measured	12 weeks