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

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

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03151005

Enrollment

Registered

2017-05-12

Start date

2017-07-01

Completion date

2021-04-23

Last updated

2023-12-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Obesity, Overweight, Polycystic Ovary Syndrome (PCOS)

Keywords

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

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.

Detailed 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.

Interventions

DRUGMetformin-GLP-1 Receptor Agonist

metformin oral with exenatide/liraglutide subcutaneous injection.

DRUGMetformin-Oral Contraceptive(OC)

metformin with Diane 35 oral intake.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

FEMALE

Age

18 Years to 50 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Assessment of Reproductive Functions	12 weeks	Concentration of LH was measured in mIU/ml.

Secondary

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

Countries

China

Participant flow

Participants by arm

Arm	Count
Metformin-Oral Contraceptive(OC) 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. Metformin-Oral Contraceptive(OC): metformin with Diane 35 oral intake.	30
Metformin-GLP-1 Receptor Agonist 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. Metformin-GLP-1 Receptor Agonist: metformin oral with exenatide/liraglutide subcutaneous injection.	30
Total	60

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Lost to Follow-up	5	5

Baseline characteristics

Characteristic	Metformin-GLP-1 Receptor Agonist	Total	Metformin-Oral Contraceptive(OC)
Age, Categorical <=18 years	3 Participants	10 Participants	7 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	27 Participants	50 Participants	23 Participants
Age, Continuous	25.73 years STANDARD_DEVIATION 4.95	24.08 years STANDARD_DEVIATION 5.35	22.43 years STANDARD_DEVIATION 5.3
Race and Ethnicity Not Collected	—	0 Participants	—
Region of Enrollment China	30 participants	60 participants	30 participants
Sex: Female, Male Female	30 Participants	60 Participants	30 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants
weight	73.95 kg STANDARD_DEVIATION 10.04	72.47 kg STANDARD_DEVIATION 10.56	70.98 kg STANDARD_DEVIATION 11.02

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 30	0 / 30
other Total, other adverse events	0 / 30	1 / 30
serious Total, serious adverse events	0 / 30	0 / 30

Arm	Measure	Value (MEAN)	Dispersion
Metformin-GLP-1 Receptor Agonist	Basic Vital Signs	26.26 kg/m^2	Standard Deviation 3.67
Metformin-Oral Contraceptive(OC)	Basic Vital Signs	27.12 kg/m^2	Standard Deviation 4.04

Source: ClinicalTrials.gov · Data processed: Feb 8, 2026