Semaglutide Improves Metabolic Abnormalities and Fertility in Obese Infertile Women With Polycystic Ovary Syndrome: a Prospective, Randomized, Open, Controlled Study
Phase: PHASE4
Conditions: PCOS (Polycystic Ovary Syndrome), Semaglutide
Sponsor: Peking University First Hospital

 
Study Protocol  
 
 
 
Official Title: Semaglutide Improves Metabolic Abnormalities and 
Fertility in Obese Infertile Women With Polycystic Ovary 
Syndrome: a Prospective, Randomized, Open, Controlled 
Study 
 
NCT number: Not assigned yet 
 
Document Date: Jan 18th, 2023 
 
 
 
 
 
 
 
 
 

Study Protocol 
 
This study is a prospective, randomized, open and controlled study. 75 
obese infertile patients with polycystic ovary syndrome (PCOS) will be 
recruited , and all will receive energy restriction balanced diet and 
physical exercise guidance. In a 1:1:1 ratio, all subjects will be 
randomized to three groups: metformin single, semaglutide single and 
metformin combined with semaglutide group, with 25 subjects in each 
group. 
 
Metformin and semaglutide are administered in a dose-increasing mode. 
The initial dose of metformin is 500mg Bid (twice daily), increased to 
1000mg Bid after 2 weeks, and then maintained until the end of 12 weeks 
of treatment. Semaglutide is injected subcutaneously. The initial dose is 
0.25 mg QW (once a week), increased to 0.5 mg QW after 4 weeks, and 
increased to 1.0 mg QW after another 4 weeks, and then maintained until 
the end of 12 weeks of treatment.  All patients will be treated for 12 
weeks, and the metabolism-related indexes will be evaluated. After 8 
weeks of drug withdrawal, all patients will start ovulation induction or 
ovulation induction combined with artificial insemination treatment, and 
then followed up for another 24 weeks to record the pregnancy and 
evaluate the fertility related indicators. 

 
Coprimary endpoints are percentage change in bodyweight and 
achievement of weight reduction of at least 5% at 12 weeks for 
semaglutide versus metformin. The secondary endpoints include HOMA-
IR and androgen levels at 12 weeks, depression, anxiety, diet and quality 
of life scores at 12 weeks of treatment, and ovulation rate, clinical 
pregnancy rate and cumulative pregnancy rate at 24 weeks of follow-up. 
 
 
 
Inclusion Criteria: 
∙ 
Age 22-40 
∙ 
Meet the PCOS diagnostic criteria (Rotterdam） 
∙ 
BMI ≥ 28 kg/m2 
∙ 
Infertility: having normal sexual life and failing to conceive without 
contraception for more than 1 year 

∙ 
Willing to be pregnant, and her husband has no serious infertility 
 
Exclusion Criteria: 
∙ 
History of acute pancreatitis, individual or family history of 
medullary thyroid cancer and multiple endocrine adenomas 
∙ 
Type 1 diabetes and special type diabetes 
∙ 
History of tumor 
∙ 
Serious cardiovascular and cerebrovascular disease, mental disease, 
liver or kidney disease 
∙ 
Metformin, GLP-1 RA and other drugs affecting reproductive and 
metabolic functions were used within 90 days before the study 
∙ 
Known allergy to metformin, GLP-1 RA and excipients 
∙ 
Severe endometriosis, low ovarian reserve, premature ovarian failure 
∙ 
Inability to tolerate pregnancy and ovulation induction therapy 
∙ 
Other conditions considered unsuitable for this study by researchers