Semaglutide Improves Metabolic Abnormalities and Fertility in Obese Infertile Women With Polycystic Ovary Syndrome

Peking University

Status and phase: Enrolling; Phase 4

Conditions: Semaglutide; PCOS (Polycystic Ovary Syndrome)

Treatments: Drug: Semaglutide, 1.34 mg/mL and Metformin Hydrochloride 500 MG; Drug: Semaglutide, 1.34 mg/mL; Behavioral: calorie-restricted diet; Behavioral: physical exercise; Drug: Metformin Hydrochloride 500 MG

Study type: Interventional

Funder types: Other

Identifiers

NCT05702905

2022CR04

Details and patient eligibility

About

To investigate the efficacy of semaglutide in obese infertile women of childbearing age with polycystic ovary syndrome (PCOS), we design this prospective, randomized, open and controlled study. 75 obese infertile PCOS patients will be recruited and randomized into three groups: metformin, semaglutide and metformin+semaglutide, on the basis of calorie-restricted diet and physical exercise. All subjects will be treated for 12 weeks, and then stop taking the drug for at least 8 weeks to initiate ovulation induction or ovulation induction combined with artificial insemination. All subjects will be followed up for 24 weeks for pregnancy outcome. The primary endpoint of the study is the percentage of weight loss at 12 weeks of treatment. The secondary endpoints include HOMA-IR and androgen levels at 12 weeks of treatment, ovulation rate at 24 weeks of follow-up, clinical pregnancy rate and cumulative pregnancy rate, and depression, anxiety, diet and quality of life scores at 12 weeks of treatment.

Full description

To investigate the efficacy of semaglutide in obese infertile women of childbearing age with polycystic ovary syndrome (PCOS), we design this prospective, randomized, open and controlled study. 75 obese infertile PCOS patients will be recruited and randomized into three groups: metformin, semaglutide and metformin+semaglutide, on the basis of calorie-restricted diet and physical exercise. Metformin and semaglutide will be administered in a dose increasing mode, and then maintain until the end of 12 weeks, and metabolic related indexes will be evaluated. After 12 weeks of treatment, all subjects will stop taking the drug for at least 8 weeks to initiate ovulation induction or ovulation induction combined with artificial insemination. All subjects will be followed up for 24 weeks to evaluate the fertility related indicators. The primary endpoint of the study is the percentage of weight loss at 12 weeks of treatment. The secondary endpoints include HOMA-IR and androgen levels at 12 weeks of treatment, ovulation rate at 24 weeks of follow-up, clinical pregnancy rate and cumulative pregnancy rate, and depression, anxiety, diet and quality of life scores at 12 weeks of treatment.

Enrollment: 75 estimated patients

Sex: Female

Ages: 22 to 40 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Meet the PCOS diagnostic criteria (Rotterdam）
2. Age 22-40
3. BMI ≥ 28 kg/m2
4. Infertility: having normal sexual life and failing to conceive without contraception for more than 1 year
5. Willing to be pregnant, and her husband has no serious infertility

Exclusion criteria

1. History of acute pancreatitis, individual or family history of medullary thyroid cancer and multiple endocrine adenomas
2. Type 1 diabetes and special type diabetes
3. History of tumor
4. Serious cardiovascular and cerebrovascular disease, mental disease, liver or kidney disease
5. Metformin, GLP-1 RA and other drugs affecting reproductive and metabolic functions were used within 90 days before the study
6. Known allergy to metformin, GLP-1 RA and excipients
7. Severe endometriosis, low ovarian reserve, premature ovarian failure
8. Inability to tolerate pregnancy and ovulation induction therapy
9. Other conditions considered unsuitable for this study by researchers

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

75 participants in 3 patient groups

metformin

Active Comparator group

Description:

About 25 subjects will be allocated to this group to receive metformin only, as the active comparator of semaglutide groups. Metformin used in this trial is Glucophage ( 500mg per tablet）produced by Bristol-Myers Squibb.The initial dose of metformin will be 500mg twice daily, which will be increased to 1000mg twice daily after two weeks, and then maintained until the end of treatment in total 12 weeks.

Treatment:

Drug: Metformin Hydrochloride 500 MG

Behavioral: calorie-restricted diet

Behavioral: physical exercise

semaglutide

Experimental group

Description:

About 25 subjects will be allocated to this group to receive semaglutide only, as one of the experimental groups. Semaglutide used in this trial is WEGOVY (semaglutide) injection produced by Novo Nordisk. Administer WEGOVY once weekly, on the same day each week, at any time of day, with or without meals. Inject subcutaneously in the abdomen, thigh or upper arm. Initiate at 0.25 mg once weekly for 4 weeks. In 4 week intervals, increase the dose until a dose of 1.0 mg is reached, and then maintained 1.0 mg until the end of treatment in total 12 weeks..

Treatment:

Behavioral: calorie-restricted diet

Behavioral: physical exercise

Drug: Semaglutide, 1.34 mg/mL

semaglutide and metformin

Experimental group

Description:

About 25 subjects will be allocated to this group to receive both semaglutide and metformin, as another of the experimental groups. Metformin used in this trial is Glucophage ( 500mg per tablet）produced by Bristol-Myers Squibb.The initial dose of metformin will be 500mg twice daily, which will be increased to 1000mg twice daily after two weeks, and then maintained until the end of treatment in total 12 weeks. Semaglutide used in this trial is WEGOVY (semaglutide) injection produced by Novo Nordisk. Administer WEGOVY once weekly, on the same day each week, at any time of day, with or without meals. Inject subcutaneously in the abdomen, thigh or upper arm. Initiate at 0.25 mg once weekly for 4 weeks. In 4 week intervals, increase the dose until a dose of 1.0 mg is reached, and then maintained 1.0 mg until the end of treatment in total 12 weeks.

Treatment:

Behavioral: calorie-restricted diet

Behavioral: physical exercise

Drug: Semaglutide, 1.34 mg/mL and Metformin Hydrochloride 500 MG