Liraglutide and Metformin Combination on Weight Loss, Metabolic - Endocrine Parameters and Pregnancy Rate in Women With PCOS, Obesity and Infertility

NCT ID: NCT05952882

Last Updated: 2023-10-23

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 188 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-11-01
• Study Completion Date: 2025-12-31

Brief Summary

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age and one of the leading causes of infertility. PCOS and obesity affect up to 12.5% - 48.3% Asian women, increase incidence of impaired glucose tolerance, type 2 diabetes and aggravate insulin resistance, cause ovulatory dysfunction and menstrual disorders, and negatively impact outcomes of Assited Reproductive Technology (ART), with higher miscarriage rate when receiving ART. Weight loss decrease insulin resistance and hyperandrogenism, improve ovulation rate and menstrual cycle, significantly higher conception and live birth rates. Weight loss prior to IVF procedures has been associated with significantly improved pregnancy rates (PR) and live birth rates. Furthermore, a decreased number of IVF cycles required to achieve a pregnancy has also been reported after weight loss interventions. Based on the principles of fetal programming, improving a lifestyle before conception might lead to improved longterm health of the offspring. Studies on the effect of anti-obesity medication combined with lifestyle changes on body weight and composition and metabolic - endocrine parameters and pregnancy rate in obese women diagnosed with PCOS are lacking. There is a growing need to develop pharmacologic interventions to improve metabolic function in women with polycystic ovary syndrome (PCOS).

Detailed Description

The drug, liraglutide 3.0 mg was approved for chronic weight management in management in obese adults with an initial BMI of 30 kg/m2 or greater or in overweight adults BMI of 27 kg/m2 or greater with at least one weight-related co-morbid condition as an adjunct to a reduced-calorie diet and increased physical activity. Liraglutide is an acylated human glucagon-like peptide -1 (GLP-1) analog that binds to and activates the GLP-1 receptor. It lowers body weight through decreased caloric intake while stimulating insulin secretion and reducing glucagon via a glucose-dependent mechanism. For obesity management, patients may lose weight with GLP-1 receptor agonists due to other unique actions. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) can slow gastric emptying and increase satiety. While predictors of weight loss success for the general population are available (protein intake, weight loss medications), predictors of weight loss success may differ between normal and hyperandrogenic women. Glucagon-like peptide 1 agonists are linked with dose dependent weight lowering potential in different obesity related populations. The weight loss effects of GLP-1RAs previously demonstrated in diabetic and obese non-diabetic patients, offer a unique opportunity to expand the medical options available to patients with PCOS. Metformin was recommended for women with PCOS and obesity (BMI ≥ 25 kg/m2) or at metabolic risks and shown beneficial effects on menstrual disorders, anovulation, hyperandrogenism, and cardiovascular abnormalities.

The aim of this study was to evaluate the impact of liraglutide in combination with metformin compared to metformin alone on weight reduction, the multifaceted metabolic - endocrine disturbances, and oocyte and embryo quality, IVF PRs and cumulative PRs (IVF and spontaneous pregnancies) in infertile obese women with PCOS who had been previously poor responders to weight reduction with lifestyle modification.

Conditions

Polycystic Ovary Syndrome; Obesity; Infertility, Female

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

LIME 3mg/1500mg

Metformin XR (extended-release) was initiated with a dose of 750 mg once per day for 2 week and increased to 1500 mg once per day for up to 12 weeks. Start injection liraglutide 0.6 mg subcutaneously (SC) 1week daily (QD), then titrated in increments of 0.6 mg once daily every 1 to 3 weeks to a final dose of 3.0 mg liraglutide SC daily for up to 12 weeks.

Group Type: EXPERIMENTAL

Liraglutide + Metformin

Intervention Type: DRUG

Metformin XR (extended-release) was initiated at 750 mg once daily and increased to 1500 mg once daily after 2 week. Concomitantly, Liraglutide was initiated at a subcutaneous dose of 0.6 mg once daily for 1 week, then titrated in increments of 0.6 mg once daily every 1 to 3 weeks to a maintenance dose of 3.0 mg once daily for up to 12 weeks

MET 1500mg

Metformin XR (extended-release) was initiated with a dose of 750 mg once per day for 2 week and increased to 1500 mg once per day for up to 12 weeks

Group Type: ACTIVE_COMPARATOR

Metformin

Intervention Type: DRUG

Metformin XR (extended-release) was initiated at 750 mg once daily and increased to 1500 mg once daily after 2 week

Interventions

Liraglutide + Metformin

Metformin XR (extended-release) was initiated at 750 mg once daily and increased to 1500 mg once daily after 2 week. Concomitantly, Liraglutide was initiated at a subcutaneous dose of 0.6 mg once daily for 1 week, then titrated in increments of 0.6 mg once daily every 1 to 3 weeks to a maintenance dose of 3.0 mg once daily for up to 12 weeks

Intervention Type: DRUG

Metformin

Metformin XR (extended-release) was initiated at 750 mg once daily and increased to 1500 mg once daily after 2 week

Intervention Type: DRUG

Other Intervention Names

LIME; MET

Eligibility Criteria

Inclusion Criteria

• Female gender
• 18-65 years of age
• Diagnosis of polycystic ovary syndrome according to the revised Rotterdam criteria (2003)
• BMI ≥ 27 kg/m2
• Infertility
• Agree to participate in the study

Exclusion Criteria

• Type 1 or type 2 diabetes.
• History of acute or chronic pancreatitis.
• Family or individual history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2
• Known hypersensitivity or contraindication to the use of GLP-1 receptor agonists.
• Used of hormonal drugs, drugs causing clinically significant weight changes and drugs affecting glucose tolerance for at least 8 weeks.
• Used a anti-androgen drugs for at least 4 weeks.
• History of malignancy requiring chemotherapy.
• History of taking antidiabetic drugs other than gestational diabetes or weight-loss drugs discontinued for at least 4 weeks.
• History of gastrectomy or device-based intervention to manage obesity
• Eating disorders (anorexia or bulimia) or digestive disorders.
• Substance abuse (Tobacco or alcohol)
• History of major depression or other serious mental disorder.
• Inability or refusal to adhere treatment regimens.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Mỹ Đức Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

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Other Identifiers

08/23/DD-BVMD

Identifier Type: -

Identifier Source: org_study_id