Liraglutide Treatment in Obese Infertile PCOS Women (LITOP)

Liraglutide, a hypoglycemic drug, can reduce weight and improve insulin resistance while stabilizing blood glucose metabolism without increasing the risk of hypoglycemia, and has been approved by the State Food and Drug Administration of China and the US Food and Drug Administration for the treatment of obesity. Polycystic ovary syndrome (PCOS) is the main cause of female anovulatory infertility, and it is also a high-risk group of obesity. Previous studies have suggested that liraglutide improves glucose metabolism, body weight, and inflammation levels in obese women with PCOS, and improves sex hormone profiles and menstrual cycles, possibly contributing to increased fertility.

Therefore, this project intends to test the following hypothesis through a large sample randomized controlled trial in obese and infertile PCOS women who are assisted by in vitro fertilization-frozen embryo transfer (IVF-FET), using liraglutide before transplantation to reduce weight can improve the live birth rate of assisted reproduction.

Study Overview

• Status: Recruiting
• Conditions: Obesity; Infertility; PCOS
• Intervention / Treatment: Drug: Liraglutide and metformin; Drug: Metformin

• Study Type: Interventional
• Enrollment (Estimated): 890
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Haining Wang, Professor; Phone Number: 8601082265025; Email: hainingmail@bjmu.edu.cn
• Study Contact Backup: Name: Ye Liu, Associate Professor; Phone Number: 8601082265025; Email: yeliumed@bjmu.edu.cn

Study Locations

• China
  • Beijing, China
    • Not yet recruiting
    • Beijing obstetrics and gynecology hospital
    • Contact: Prof. Yang; Phone Number: 8601052276699; Email: xiaokuiyang2012@163.com
  • Beijing, China
    • Not yet recruiting
    • Haidian District Maternal and Child Health Care Hospital
    • Contact: Prof. Liu; Phone Number: 8601062538899
  • Beijing
    • Beijing, Beijing, China
      • Recruiting
      • Peking University Third Hospital
      • Contact: Ye Liu; Phone Number: 8601082265025; Email: yeliumed@bjmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Women with polycystic ovary syndrome (PCOS) who meet the Rotterdam diagnostic criteria.
• Aged 20-40 years;
• 25 kg/m2 ≤ BMI ≤ 35 kg/m2;
• Have not used any anti-diabetes or weight-loss medications (metformin excluded) within the past 3 months;
• Have at least 1 transplantable frozen embryo available at the research center;
• Able to follow the study's contraceptive requirements.

Exclusion Criteria:

• Diabetic ketoacidosis or other acute complications of diabetes;
• HbA1c ≥ 9.0% before enrollment;
• Using drugs that affect appetite or nutrient absorption within the past 2 months (metformin excluded);
• Uncontrolled hyperthyroidism or hypothyroidism, hypertension, systemic autoimmune diseases, etc. that may affect pregnancy and fetal development;
• 17 hydroxyprogesterone in follicualr phase > 2.0 ng/ml;
• Serious cardiovascular, digestive, liver, or kidney diseases, HBsAg-positive chronic hepatitis B, active pulmonary tuberculosis, or AIDS, etc. that are infectious or hereditary diseases;
• Any psychiatric or psychological disorders requiring drug treatment;
• Poor pregnancy and delivery history: recurrent failed implantations ≥3 times, spontaneous abortions ≥2 times; history of stillbirth, dystocia, or birth defects; previous pregnancies with preeclampsia, eclampsia, or HELLP syndrome;
• Uncontrolled metabolic, autoimmune, or hereditary disease in the husband;
• A contraindication or relative contraindication to using GLP-1 receptor agonists (history of medullary thyroid carcinoma or family history of medullary thyroid carcinoma, acute cholecystitis or pancreatitis in the acute phase or history of previous attacks, GLP-1 receptor agonist allergy, etc.);
• Failure to comply with the contraceptive requirements of the study design;
• Failure to take medication regularly and follow up;
• Current smokers, drug addicts, alcoholics, or individuals with substance abuse;
• Participants who have participated in any clinical trial within the past 3 months prior to screening;
• Individuals with other conditions deemed unsuitable for participation in this clinical trial by the investigator;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention Group; Liraglutide 3.0 mg or maximum tolerable dose/day and metformin 1500 mg/day	Drug: Liraglutide and metformin; Liraglutide 3.0 mg or maximum tolerable dose/day × 12 weeks and metformin 1500 mg/day until pregnancy.
Active Comparator: Control Group; Metformin 1500 mg/day	Drug: Metformin; Metformin 1500 mg/day until pregnancy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Live birth rate associated with single cycle frozen embryo transfer	The rate of live birth of intervention and control groups	At delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical pregnancy rate of single cycle frozen embryo transfer	Viable intrauterine pregnancy confirmed by ultrasound	Thirty days after the embryo transplantation
Incidence of newly diagnosed diabetes or gestational diabetes during pregnancy	Newly diagnosed diabetes or gestational diabetes at 28 weeks of pregnancy confirmed by 75 g oral glucose tolerance test。	At 28 weeks of pregnancy
Pregnancy outcome and complications	Rate of miscarriage, multiple pregnancies, pregnancy induced hypertension, preeclampsia, HELLP syndrome, prematurity (< 37 weeks), macrosomia (birth weight > 4 kg), induction of labour, prolonged duration of labour, caesarean section, assisted delivery, peripartum increased blood loss (≥ 800 ml).	From baseline to delivery
Birth weight for gestational age	Birth weight percentile for gestational age for neonatal sex	At delivery
Apgar scores	Apgar scores (0~10) of the newborns at delivery	At delivery
Other perinatal outcomes	Rate of major birth defects, stillbirth, neonatal complications, and neonatal admission to a neonatal intensive care unit.	At delivery
Accumulated live birth rate	Accumulated liver birth rate associated with the pregnancy achieved during the first 6 months of the study	At delivery
Accumulated clinical pregnancy rate	Accumulated clinical pregnancy rate achieved during the first 6 months of the study	At month 6

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight	Measured by the same weight scale	At baseline, and week 12
Oral glucose tolerance test	oral glucose tolerance test was conducted to test glucose metabolism	At baseline, week 12, 28 weeks of pregnant, six weeks after delivery
HbA1c	Glycosylated hemoglobin	At baseline and week12
Rate of insulin usage during pregancy		Throughout pregnancy
Number of menstrual cycles		From to 12 weeks
Free testosterone index	Free testosterone index	At baseline, week 12
Drug-related adverse reactions	Drug-related adverse reactions, including but not limited to, nausea, diarrhea, vomiting, decreased appetite, dyspepsia, constipation, drug allergy, hypoglycemia, acute pancreatitis, acute gallbladder disease.	During the treatment with liraglutide or metformin
Anxiety	Measured by Generalized Anxiety Disorder-7 scores, from 0 (no anxiety) to 21 (severe anxiety)	Baseline and week 12
Depression	Measured by Patient Health Questionnaire-9 score from 0 (no depression) to 27 (severe depression)	Baseline and week 12
Quality of life specifically for PCOS individuals	Measured by Modified Polycystic ovary syndrome Quality of life, with each item scores from 1 (maximum impairment) to 7 (no impairment)	Baseline and week 12
Major congenital malformations	Identified in the Birth Defects Prevention and Control Plan (2023-2027) issued by the National Health Commission of the People's Republic of China	Six weeks after live birth
Costs	The cost per live birth for the different intervention groups, considering both direct medical and non-medical costs, as well as indirect costs.	At delivery

Collaborators and Investigators

• Sponsor: Peking University Third Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 2025
• Primary Completion (Estimated): May 30, 2029
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: August 4, 2024
• First Submitted That Met QC Criteria: December 18, 2024
• First Posted (Actual): December 19, 2024

Study Record Updates

• Last Update Posted (Actual): May 29, 2025
• Last Update Submitted That Met QC Criteria: May 22, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: polycystic ovary syndrome; obesity; liraglutide; infertile
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Infertility; Glucagon-Like Peptide-1 Receptor Agonists; Physiological Effects of Drugs; Hypoglycemic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Liraglutide; Metformin
• Other Study ID Numbers: LITOP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: De-identified individual participant data will be available if researchers provide a methodologically sound proposal and contact to the principal investigator. Data requestors will need to sign a data access agreement.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No