Clinical trial NCT05952882: Liraglutide and Metformin Combination on Weight Loss, Metabolic - Endocrine Parameters and Pregnancy Rate in Women With PCOS, Obesity and Infertility
Official title: Effectiveness of the Combination Liraglutide and Metformin on Weight Loss, Metabolic - Endocrine Parameters and Pregnancy Rate in Women With Polycystic Ovarian Syndrome, Obesity and Infertility
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Polycystic Ovary Syndrome
Obesity
Infertility, Female
Keywords: Polycystic Ovary Syndrome
GLP-1 agonist
Liraglutide
obesity
weight loss
insulin resistance
androgens
pregnancy rates
In Vitro Fertilization
Lead sponsor: Mỹ Đức Hospital
Sponsor class: OTHER
First posted: 2023-07-19
Enrollment: 188
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Absolute Body Weight (BW)
timeFrame: 12 weeks of treatment
measure: Change in Percent Body Weight
timeFrame: 12 weeks of treatment
Secondary outcomes:
measure: Body Mass Index (BMI)
timeFrame: 12 weeks of treatment
measure: Abdominal Adiposity (Waist Circumference [WC])
timeFrame: 12 weeks of treatment
measure: Waist-to-Hip Ratio (WHR)
timeFrame: 12 weeks of treatment
measure: Waist-to Height Ratio [WHtR]
timeFrame: 12 weeks of treatment
measure: Total Fat Mass Evaluated by BIA
timeFrame: 12 weeks of treatment
measure: Total Body Fat (%) by BIA (Bioelectrical Impedance Analysis) machine
timeFrame: 12 weeks of treatment
measure: Visceral Fat Level (VFL)
timeFrame: 12 weeks of treatment
measure: Total lean body mass
timeFrame: 12 weeks of treatment
measure: Glucose OGTT 0 min
timeFrame: 12 weeks of treatment
measure: Glucose OGTT 120 min
timeFrame: 12 weeks of treatment
measure: Insulin OGTT 0 min
timeFrame: 12 weeks of treatment
measure: Insulin OGTT 120 min
timeFrame: 12 weeks of treatment
measure: Fasting Insulin Sensitivity (HOMA-IR)
timeFrame: 12 weeks of treatment
measure: Matsuda Insulin Sensitivity Index Derived From the OGTT (SI OGTT)
timeFrame: 12 weeks of treatment
measure: Total Cholesterol Levels
timeFrame: 12 weeks of treatment
measure: High Density Lipoprotein Cholesterol (HDL-C)
timeFrame: 12 weeks of treatment
measure: Triglyceride Levels (TRG)
timeFrame: 12 weeks of treatment
measure: Low Density Lipoprotein Cholesterol (LDL-C)
timeFrame: 12 weeks of treatment
measure: Systolic Blood Pressure
timeFrame: 12 weeks of treatment
measure: Diastolic Blood Pressure
timeFrame: 12 weeks of treatment
measure: Menstrual Cycle Frequency
timeFrame: 12 weeks of treatment
measure: Free Androgen Index (FAI)
timeFrame: 12 weeks of treatment
measure: Total Testosterone Concentrations (T)
timeFrame: 12 weeks of treatment
measure: Sex Hormone Binding Globulin (SHBG)
timeFrame: 12 weeks of treatment
measure: Adrenal Dehydroepiandrosterone Sulfate (DHEAS)
timeFrame: 12 weeks of treatment
measure: 17(OH)-progesterone
timeFrame: 12 weeks of treatment
measure: Androstenedione
timeFrame: 12 weeks of treatment
measure: Progesterone
timeFrame: 12 weeks of treatment
measure: Luteinizing Hormone (LH)
timeFrame: 12 weeks of treatment
measure: Follicle Stimulating Hormone (FSH)
timeFrame: 12 weeks of treatment
measure: Ovary Volume
timeFrame: 12 weeks of treatment
measure: Spontaneous Pregnancy Rate
timeFrame: 12 months after treatment
measure: Assisted Reproductive Therapy Pregnancy Rate
timeFrame: 12 months after treatment
measure: Cumulative Pregnancy Rate
timeFrame: 12 months after treatment
measure: Total dosage gonadotropin (GNT)
timeFrame: 12 weeks of treatment
measure: No. of retrieved oocytes/patient
timeFrame: 12 weeks of treatment
measure: No. of mature (MII) oocytes/patient
timeFrame: 12 weeks of treatment
measure: Fertilization rate
timeFrame: 12 weeks of treatment
measure: Oocyte degeneration rate
timeFrame: 12 weeks of treatment
measure: Immaturity rate
timeFrame: 12 weeks of treatment
measure: No. of embryos on day 5/patient
timeFrame: 12 weeks of treatment
measure: No. of blastocysts/patient
timeFrame: 12 weeks of treatment
measure: Blastulation rate
timeFrame: 12 weeks of treatment
measure: No. of transferred embryos
timeFrame: 12 weeks of treatment
measure: Pregnancy rate per cycle
timeFrame: 12 weeks of treatment
measure: Pregnancy rate per Embryo Transfer (ET)
timeFrame: 12 weeks of treatment
measure: Implantation rate
timeFrame: 12 weeks of treatment
measure: No. of cancelled fresh Embryo Transfer (ET) because of hyperstimulation risk
timeFrame: 12 weeks of treatment
measure: Cryopreservation
timeFrame: 12 weeks of treatment
measure: No. of cryopreserved embryos/patient
timeFrame: 12 weeks of treatment
measure: Ectopic Pregnancy Rate
timeFrame: 12 weeks of treatment
measure: Stillbirth Rate
timeFrame: 24 months after treatment
measure: Abortion Rate
timeFrame: 24 months after treatment
measure: Gestational Diabetes Mellitus Rate
timeFrame: 24 months after treatment
measure: Gestational hypertensive disorder (GHD) Rate
timeFrame: 24 months after treatment
measure: Live Birth Rate
timeFrame: 24 months after treatment
measure: Gestational age at birth
timeFrame: 24 months after treatment
measure: Type of Delivery Method
timeFrame: 24 months after treatment
Other outcomes:
Locations:
Study officials:
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