Liraglutide and Metformin Combination on Weight Loss, Metabolic - Endocrine Parameters and Pregnancy Rate in Women With PCOS, Obesity and Infertility
- Conditions
- Polycystic Ovary SyndromeObesityInfertility, Female
- Interventions
- Registration Number
- NCT05952882
- Lead Sponsor
- Mỹ Đức Hospital
- 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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- Female
- Target Recruitment
- 188
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description LIME 3mg/1500mg Liraglutide + Metformin 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. MET 1500mg Metformin 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
- Primary Outcome Measures
Name Time Method Absolute Body Weight (BW) 12 weeks of treatment Treatment impact on change in body weight after 12 weeks of treatment.
Change in Percent Body Weight 12 weeks of treatment Treatment effect on reducing body weight expressed as percent body weight loss from baseline
- Secondary Outcome Measures
Name Time Method Body Mass Index (BMI) 12 weeks of treatment Treatment effect in reducing body mass
Total dosage gonadotropin (GNT) 12 weeks of treatment Drug treatment impact on total dosage GNT
Abdominal Adiposity (Waist Circumference [WC]) 12 weeks of treatment Treatment effect on loss of waist circumference (abdominal adiposity) with drug treatment
Waist-to-Hip Ratio (WHR) 12 weeks of treatment Change in central adiposity with treatment as measured by waist-to-hip ratio. A reduction in ratio indicates a decrease in truncal fat.
Waist-to Height Ratio [WHtR] 12 weeks of treatment Treatment effect on loss of central adiposity as determined by Waist-to Height Ratio. The lower the ratio indicates less abdominal adiposity.
Matsuda Insulin Sensitivity Index Derived From the OGTT (SI OGTT) 12 weeks of treatment The SI OGTT is a measure of peripheral insulin sensitivity derived from the insulin and glucoses measured during an OGTT. A increase in SI OGTTindicates greater insulin sensitivity
Visceral Fat Level (VFL) 12 weeks of treatment Treatment effect on reduction of visceral fat level by BIA
Fasting Insulin Sensitivity (HOMA-IR) 12 weeks of treatment Treatment effect on the HOMA-IR which is an insulin resistance measured derived from fasting blood glucose and insulin . The higher the number the more insulin resistant.
Total Testosterone Concentrations (T) 12 weeks of treatment Drug treatment effect on total testosterone concentrations
Total Fat Mass Evaluated by BIA 12 weeks of treatment Treatment effect on reduction of fat mass (kg)
Triglyceride Levels (TRG) 12 weeks of treatment Drug effect of TRG levels after treatment
Total Body Fat (%) by BIA (Bioelectrical Impedance Analysis) machine 12 weeks of treatment Treatment effect on reduction of percent body fat by BIA
Total lean body mass 12 weeks of treatment Treatment impact on total lean body mass
Glucose OGTT 0 min 12 weeks of treatment Treatment effect on fasting glucose prior to an oral glucose tolerance test (OGTT)
Insulin OGTT 120 min 12 weeks of treatment Treatment effect on insulin measured at 120 minutes of an oral glucose tolerance test (OGTT)
High Density Lipoprotein Cholesterol (HDL-C) 12 weeks of treatment Impact of treatment on HDL levels after 12 weeks of treatment
Systolic Blood Pressure 12 weeks of treatment Treatment impact on systolic blood pressure
Adrenal Dehydroepiandrosterone Sulfate (DHEAS) 12 weeks of treatment Treatment efficacy in reducing adrenal hyperandrogenism
Luteinizing Hormone (LH) 12 weeks of treatment Drug treatment effect on LH
Follicle Stimulating Hormone (FSH) 12 weeks of treatment Drug treatment effect on FSH
No. of mature (MII) oocytes/patient 12 weeks of treatment Drug treatment impact on No. of mature (MII) oocytes/patient
Oocyte degeneration rate 12 weeks of treatment Drug treatment impact on oocyte degeneration rate
Diastolic Blood Pressure 12 weeks of treatment Treatment impact on reducing diastolic blood pressure
Androstenedione 12 weeks of treatment Drug treatment effect on androstenedione
Ovary Volume 12 weeks of treatment Treatment efficacy in reducing ovary volume
Spontaneous Pregnancy Rate 12 months after treatment Treatment effect on spontaneous pregnancy rate
Assisted Reproductive Therapy Pregnancy Rate 12 months after treatment Treatment effect on Assisted Reproductive Therapy Pregnancy Rate
Immaturity rate 12 weeks of treatment Drug treatment impact on immaturity rate
No. of blastocysts/patient 12 weeks of treatment Drug treatment impact on No. of blastocysts/patient
No. of cancelled fresh Embryo Transfer (ET) because of hyperstimulation risk 12 weeks of treatment Drug treatment impact on No. of cancelled fresh Embryo Transfer (ET because of hyperstimulation risk
Cryopreservation 12 weeks of treatment Drug treatment impact on cryopreservation
Glucose OGTT 120 min 12 weeks of treatment Treatment effect on glucose measured at 120 minutes of an oral glucose tolerance test (OGTT)
Insulin OGTT 0 min 12 weeks of treatment Treatment effect on fasting insulin prior to an oral glucose tolerance test (OGTT)
Total Cholesterol Levels 12 weeks of treatment Treatment impact on improving total cholesterol levels
Low Density Lipoprotein Cholesterol (LDL-C) 12 weeks of treatment Treatment impact on improving LDL-C after treatment
Menstrual Cycle Frequency 12 weeks of treatment Drug treatment impact on normalization of cycle frequency (cycle every 28-30 days). All cycle data is expressed as number of menses annualized to one year.
Free Androgen Index (FAI) 12 weeks of treatment Drug treatment effect on free androgen levels as calculated as FAI= total testosterone (T) concentrations divided by sex hormone binding globulin (SHBG) levels. A higher score indicates a worse outcome (more androgenic).
Sex Hormone Binding Globulin (SHBG) 12 weeks of treatment Drug treatment effect on SHBG
17(OH)-progesterone 12 weeks of treatment Treatment efficacy in reducing adrenal hyperandrogenism
Progesterone 12 weeks of treatment Drug treatment effect on progesterone
Cumulative Pregnancy Rate 12 months after treatment Treatment effect on Cumulative Pregnancy Rate
Blastulation rate 12 weeks of treatment Drug treatment impact on blastulation rate
No. of cryopreserved embryos/patient 12 weeks of treatment Drug treatment impact on No. of cryopreserved embryos/patient
Ectopic Pregnancy Rate 12 weeks of treatment Drug treatment impact on Ectopic Pregnancy Rate
Stillbirth Rate 24 months after treatment Drug treatment impact on Stillbirth Rate
No. of retrieved oocytes/patient 12 weeks of treatment Drug treatment impact on No. of retrieved oocytes/patient
Pregnancy rate per cycle 12 weeks of treatment Drug treatment impact on pregnancy rate per cycle
Pregnancy rate per Embryo Transfer (ET) 12 weeks of treatment Drug treatment impact on pregnancy rate per ET
Type of Delivery Method 24 months after treatment Drug treatment impact on Type of Delivery Method
Fertilization rate 12 weeks of treatment Drug treatment impact on fertilization rate
No. of transferred embryos 12 weeks of treatment Drug treatment impact on No. of transferred embryos
No. of embryos on day 5/patient 12 weeks of treatment Drug treatment impact on No. of embryos on day 5/patient
Implantation rate 12 weeks of treatment Drug treatment impact on implantation rate
Abortion Rate 24 months after treatment Drug treatment impact on Abortion Rate
Gestational Diabetes Mellitus Rate 24 months after treatment Drug treatment impact on Gestational Diabetes Mellitus Rate
Gestational hypertensive disorder (GHD) Rate 24 months after treatment Drug treatment impact on Gestational hypertensive disorder (GHD) Rate
Live Birth Rate 24 months after treatment Drug treatment impact on Live Birth Rate
Gestational age at birth 24 months after treatment Drug treatment impact on gestational age at birth