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
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 188
- 主要终点
- Absolute Body Weight (BW)
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Liraglutide + Metformin (Drug)
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
干预措施: Metformin (Drug)
结局指标
主要结局
Absolute Body Weight (BW)
时间窗: 12 weeks of treatment
Treatment impact on change in body weight after 12 weeks of treatment.
Change in Percent Body Weight
时间窗: 12 weeks of treatment
Treatment effect on reducing body weight expressed as percent body weight loss from baseline
次要结局
- Body Mass Index (BMI)(12 weeks of treatment)
- Total dosage gonadotropin (GNT)(12 weeks of treatment)
- Abdominal Adiposity (Waist Circumference [WC])(12 weeks of treatment)
- Waist-to-Hip Ratio (WHR)(12 weeks of treatment)
- Waist-to Height Ratio [WHtR](12 weeks of treatment)
- Matsuda Insulin Sensitivity Index Derived From the OGTT (SI OGTT)(12 weeks of treatment)
- Visceral Fat Level (VFL)(12 weeks of treatment)
- Fasting Insulin Sensitivity (HOMA-IR)(12 weeks of treatment)
- Total Testosterone Concentrations (T)(12 weeks of treatment)
- Total Fat Mass Evaluated by BIA(12 weeks of treatment)
- Triglyceride Levels (TRG)(12 weeks of treatment)
- Low Density Lipoprotein Cholesterol (LDL-C)(12 weeks of treatment)
- Total Body Fat (%) by BIA (Bioelectrical Impedance Analysis) machine(12 weeks of treatment)
- Total lean body mass(12 weeks of treatment)
- Glucose OGTT 0 min(12 weeks of treatment)
- Insulin OGTT 120 min(12 weeks of treatment)
- High Density Lipoprotein Cholesterol (HDL-C)(12 weeks of treatment)
- Systolic Blood Pressure(12 weeks of treatment)
- Adrenal Dehydroepiandrosterone Sulfate (DHEAS)(12 weeks of treatment)
- Luteinizing Hormone (LH)(12 weeks of treatment)
- Follicle Stimulating Hormone (FSH)(12 weeks of treatment)
- No. of mature (MII) oocytes/patient(12 weeks of treatment)
- Oocyte degeneration rate(12 weeks of treatment)
- Diastolic Blood Pressure(12 weeks of treatment)
- Androstenedione(12 weeks of treatment)
- Ovary Volume(12 weeks of treatment)
- Spontaneous Pregnancy Rate(12 months after treatment)
- Assisted Reproductive Therapy Pregnancy Rate(12 months after treatment)
- Immaturity rate(12 weeks of treatment)
- No. of blastocysts/patient(12 weeks of treatment)
- No. of cancelled fresh Embryo Transfer (ET) because of hyperstimulation risk(12 weeks of treatment)
- Cryopreservation(12 weeks of treatment)
- Glucose OGTT 120 min(12 weeks of treatment)
- Insulin OGTT 0 min(12 weeks of treatment)
- Total Cholesterol Levels(12 weeks of treatment)
- Menstrual Cycle Frequency(12 weeks of treatment)
- Free Androgen Index (FAI)(12 weeks of treatment)
- Sex Hormone Binding Globulin (SHBG)(12 weeks of treatment)
- 17(OH)-progesterone(12 weeks of treatment)
- Progesterone(12 weeks of treatment)
- Cumulative Pregnancy Rate(12 months after treatment)
- Blastulation rate(12 weeks of treatment)
- No. of cryopreserved embryos/patient(12 weeks of treatment)
- Ectopic Pregnancy Rate(12 weeks of treatment)
- Stillbirth Rate(24 months after treatment)
- No. of retrieved oocytes/patient(12 weeks of treatment)
- Pregnancy rate per cycle(12 weeks of treatment)
- Pregnancy rate per Embryo Transfer (ET)(12 weeks of treatment)
- Type of Delivery Method(24 months after treatment)
- Fertilization rate(12 weeks of treatment)
- No. of transferred embryos(12 weeks of treatment)
- No. of embryos on day 5/patient(12 weeks of treatment)
- Implantation rate(12 weeks of treatment)
- Abortion Rate(24 months after treatment)
- Gestational Diabetes Mellitus Rate(24 months after treatment)
- Gestational hypertensive disorder (GHD) Rate(24 months after treatment)
- Live Birth Rate(24 months after treatment)
- Gestational age at birth(24 months after treatment)