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

NCT05702905 | Recruiting Phase 4 DMC

• 1 other identifier: 2022CR04
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

PCOS (Polycystic Ovary Syndrome); Semaglutide

Keywords

PCOS; semaglutide; obese; metabolic abnormality; fertility

Outcome Measures

Primary Outcomes (2)

• Percentage change in bodyweight at 12 weeks for semaglutide versus metformin

  Difference between body weight at 12 weeks and baseline divided by baseline body weight

  at the end of 12 weeks of treatment

• Achievement of weight reduction of at least 5% at 12 weeks for semaglutide versus metformin

  Proportion of patients with weight loss at least 5% at 12 weeks of treatment

  at the end of 12 weeks of treatment

Secondary Outcomes (4)

• HOMA-IR at 12 weeks of treatment

  at the end of 12 weeks of treatment

• testosterone level at 12 weeks of treatment

  at the end of 12 weeks of treatment

• androstenedione level at 12 weeks of treatment

  at the end of 12 weeks of treatment

• FAI (Free Androgen Index) at 12 weeks of treatment

  at the end of 12 weeks of treatment

Other Outcomes (7)

• Depression score by self-rating depression scale (SDS）at 12 weeks of treatment

  at the end of 12 weeks of treatment

• Anxiety score by self-rating anxiety scale (SAS）at 12 weeks of treatment

  at the end of 12 weeks of treatment

• Diet score by TFEQ-18 (three factor eating questionaire) at 12 weeks of treatment

  at the end of 12 weeks of treatment

Study Arms (3)

metformin

ACTIVE COMPARATOR

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.

Drug: Metformin Hydrochloride 500 MG; Behavioral: calorie-restricted diet; Behavioral: physical exercise

semaglutide

EXPERIMENTAL

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..

Drug: Semaglutide, 1.34 mg/mL; Behavioral: calorie-restricted diet; Behavioral: physical exercise

semaglutide and metformin

EXPERIMENTAL

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.

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

Interventions

Metformin Hydrochloride 500 MG DRUG

Metformin oral tablet (500mg per tablet) will be administered in a dose increasing mode: the initial dose 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.

Also known as: Glucophage

metformin

Semaglutide, 1.34 mg/mL DRUG

Inject semaglutide subcutaneously once weekly, on the same day each week, at any time of day, in a dose increasing mode: the initial dose of 0.25mg QW (once a week), increased to 0.5mg QW after 4 weeks, and increased to 1.0mg QW after another 4 weeks, and then maintained 1.0mg until the end of treatment in total 12 weeks.

Also known as: WEGOVY

semaglutide

Semaglutide, 1.34 mg/mL and Metformin Hydrochloride 500 MG DRUG

Both Semaglutide injection and Metformin oral tablet will be administered as described above.

Also known as: WEGOVY and Glucophage

semaglutide and metformin

calorie-restricted diet BEHAVIORAL

All subjects after randomization will be reviewed and evaluated by a nutritionist, and then will receive diet guidance. The clinical nutritionist will develop a written nutrition plan for each subject. The nutrition plan of this study adopted the method of calorie restriction diet (CRD) to develop a diet, which required 83.68 kJ/kg of energy per day, 1.2 g/kg of protein per day, 40%\~55% of carbohydrate energy supply ratio, and 20%\~30% of fat energy supply ratio, to ensure the intake of vegetables, fruits and other rich dietary fiber, and drinking more than 1.5 L per day. The nutritionist will explain the method of food exchange in detail to enrich the food types of patients. The diet diary will be distributed to each subject, and the subjects will be required to make a return visit once every four weeks, return the diet diary each time, and receive guidance according to their compliance.

metformin; semaglutide; semaglutide and metformin

physical exercise BEHAVIORAL

All subjects after randomization will be reviewed and evaluated by a trainer, and then will receive guidance of physical exercise.The trainer will formulate an exercise plan for each subject. The exercise plan consists of 30 minutes of moderate and low intensity continuous aerobic exercise every day, with a frequency of 5-7 days/week. The form of exercise can be determined according to personal hobbies, such as fast walking, jogging, climbing, swimming, etc. The exercise diary will be distributed to each subject, and the subjects are required to make a return visit once every four weeks, return the exercise diary each time, and the trainer will provide guidance to the subjects according to their compliance.

metformin; semaglutide; semaglutide and metformin

Eligibility Criteria

• Age: 22 Years - 40 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Meet the PCOS diagnostic criteria (Rotterdam）
• Age 22-40
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Peking University First Hospital: lead

Study Sites (1)

PekingUFH

Beijing, Beijing Municipality, 100034, China

RECRUITING

Related Publications (11)

• Jensterle Sever M, Kocjan T, Pfeifer M, Kravos NA, Janez A. Short-term combined treatment with liraglutide and metformin leads to significant weight loss in obese women with polycystic ovary syndrome and previous poor response to metformin. Eur J Endocrinol. 2014 Feb 7;170(3):451-9. doi: 10.1530/EJE-13-0797. Print 2014 Mar.

  PMID: 24362411 RESULT

• Jensterle M, Kravos NA, Pfeifer M, Kocjan T, Janez A. A 12-week treatment with the long-acting glucagon-like peptide 1 receptor agonist liraglutide leads to significant weight loss in a subset of obese women with newly diagnosed polycystic ovary syndrome. Hormones (Athens). 2015 Jan-Mar;14(1):81-90. doi: 10.1007/BF03401383.

  PMID: 25885106 RESULT

• Salamun V, Jensterle M, Janez A, Vrtacnik Bokal E. Liraglutide increases IVF pregnancy rates in obese PCOS women with poor response to first-line reproductive treatments: a pilot randomized study. Eur J Endocrinol. 2018 Jul;179(1):1-11. doi: 10.1530/EJE-18-0175. Epub 2018 Apr 27.

  PMID: 29703793 RESULT

• Han Y, Li Y, He B. GLP-1 receptor agonists versus metformin in PCOS: a systematic review and meta-analysis. Reprod Biomed Online. 2019 Aug;39(2):332-342. doi: 10.1016/j.rbmo.2019.04.017. Epub 2019 Apr 25.

  PMID: 31229399 RESULT

• Cena H, Chiovato L, Nappi RE. Obesity, Polycystic Ovary Syndrome, and Infertility: A New Avenue for GLP-1 Receptor Agonists. J Clin Endocrinol Metab. 2020 Aug 1;105(8):e2695-709. doi: 10.1210/clinem/dgaa285.

  PMID: 32442310 RESULT

• Xing C, Zhao H, Zhang J, He B. Effect of metformin versus metformin plus liraglutide on gonadal and metabolic profiles in overweight patients with polycystic ovary syndrome. Front Endocrinol (Lausanne). 2022 Aug 17;13:945609. doi: 10.3389/fendo.2022.945609. eCollection 2022.

  PMID: 36060969 RESULT

• Papaetis GS, Kyriacou A. GLP-1 receptor agonists, polycystic ovary syndrome and reproductive dysfunction: Current research and future horizons. Adv Clin Exp Med. 2022 Nov;31(11):1265-1274. doi: 10.17219/acem/151695.

  PMID: 35951627 RESULT

• Ge JJ, Wang DJ, Song W, Shen SM, Ge WH. The effectiveness and safety of liraglutide in treating overweight/obese patients with polycystic ovary syndrome: a meta-analysis. J Endocrinol Invest. 2022 Feb;45(2):261-273. doi: 10.1007/s40618-021-01666-6. Epub 2021 Aug 29.

  PMID: 34455568 RESULT

• Liu X, Zhang Y, Zheng SY, Lin R, Xie YJ, Chen H, Zheng YX, Liu E, Chen L, Yan JH, Xu W, Mai TT, Gong Y. Efficacy of exenatide on weight loss, metabolic parameters and pregnancy in overweight/obese polycystic ovary syndrome. Clin Endocrinol (Oxf). 2017 Dec;87(6):767-774. doi: 10.1111/cen.13454. Epub 2017 Sep 13.

  PMID: 28834553 RESULT

• Ma RL, Deng Y, Wang YF, Zhu SY, Ding XS, Sun AJ. Short-term combined treatment with exenatide and metformin for overweight/obese women with polycystic ovary syndrome. Chin Med J (Engl). 2021 Nov 3;134(23):2882-2889. doi: 10.1097/CM9.0000000000001712.

  PMID: 34732660 RESULT

• Li R, Mai T, Zheng S, Zhang Y. Effect of metformin and exenatide on pregnancy rate and pregnancy outcomes in overweight or obese infertility PCOS women: long-term follow-up of an RCT. Arch Gynecol Obstet. 2022 Nov;306(5):1711-1721. doi: 10.1007/s00404-022-06700-3. Epub 2022 Jul 13.

  PMID: 35829765 RESULT

MeSH Terms

Conditions

Polycystic Ovary Syndrome; Obesity

Interventions

Metformin; semaglutide; Caloric Restriction; Exercise

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; Overweight; 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; Diet Therapy; Nutrition Therapy; Therapeutics; Energy Intake; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Tingting Zhang, M.D.

  Peking University First Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tingting Zhang, M.D.

CONTACT

86-10-83575103; cathine@sina.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Chief Physician , Associate Professor

Model Details: All subjects will be randomized into three groups: metformin single, semaglutide single, both metformin and semaglutide.

Study Record Dates

• First Submitted: December 23, 2022
• First Posted: January 27, 2023
• Study Start: May 9, 2023
• Primary Completion: December 31, 2024
• Study Completion: June 30, 2025
• Last Updated: March 25, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)