Polycystic Ovary SyndromePhase 3NCT05952882
Liraglutide and Metformin Combination on Weight Loss, Metabolic - Endocrine Parameters and Pregnancy Rate in Women With PCOS, Obesity and Infertility
A Phase 3 study testing Liraglutide + Metformin and Metformin in people with Polycystic Ovary Syndrome and Obesity, run by Mỹ Đức Hospital.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 years, women only
- Conditions the study is for
- Polycystic Ovary Syndrome, Obesity, Infertility, Female
- What is being tested?
- Liraglutide + Metformin and Metformin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 188 participants
- Where
- No sites listed yet
- Study dates
- 1 Nov 2023to 31 Dec 2025
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 13Show fewer
- 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.
About this study
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
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).
Read the 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
- Being tested
- Liraglutide + Metformin, Metformin
- Keywords
- Polycystic Ovary Syndrome, GLP-1 agonist, Liraglutide, obesity, weight loss, insulin resistance, androgens, pregnancy rates, In Vitro Fertilization
- Medical subject headings
- Polycystic Ovary Syndrome, Obesity, Infertility, Female, Weight Loss, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Liraglutide + MetforminDrug
Also called LIME
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
MetforminDrug
Also called MET
Metformin XR (extended-release) was initiated at 750 mg once daily and increased to 1500 mg once daily after 2 week
| Study group | Role | What they receive |
|---|---|---|
| LIME 3mg/1500mg | Experimental | 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. Receives: Drug: Liraglutide + Metformin |
| MET 1500mg | Active comparator | 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 Receives: Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Absolute Body Weight (BW)
Treatment impact on change in body weight after 12 weeks of treatment.
Measured: 12 weeks of treatment
Change in Percent Body Weight
Treatment effect on reducing body weight expressed as percent body weight loss from baseline
Measured: 12 weeks of treatment
Secondary outcomes (58)
Body Mass Index (BMI)
Treatment effect in reducing body mass
Measured: 12 weeks of treatment
Abdominal Adiposity (Waist Circumference [WC])
Treatment effect on loss of waist circumference (abdominal adiposity) with drug treatment
Measured: 12 weeks of treatment
Waist-to-Hip Ratio (WHR)
Change in central adiposity with treatment as measured by waist-to-hip ratio. A reduction in ratio indicates a decrease in truncal fat.
Measured: 12 weeks of treatment
Waist-to Height Ratio [WHtR]
Treatment effect on loss of central adiposity as determined by Waist-to Height Ratio. The lower the ratio indicates less abdominal adiposity.
Measured: 12 weeks of treatment
Total Fat Mass Evaluated by BIA
Treatment effect on reduction of fat mass (kg)
Measured: 12 weeks of treatment
Total Body Fat (%) by BIA (Bioelectrical Impedance Analysis) machine
Treatment effect on reduction of percent body fat by BIA
Measured: 12 weeks of treatment
Visceral Fat Level (VFL)
Treatment effect on reduction of visceral fat level by BIA
Measured: 12 weeks of treatment
Total lean body mass
Treatment impact on total lean body mass
Measured: 12 weeks of treatment
Glucose OGTT 0 min
Treatment effect on fasting glucose prior to an oral glucose tolerance test (OGTT)
Measured: 12 weeks of treatment
Glucose OGTT 120 min
Treatment effect on glucose measured at 120 minutes of an oral glucose tolerance test (OGTT)
Measured: 12 weeks of treatment
Insulin OGTT 0 min
Treatment effect on fasting insulin prior to an oral glucose tolerance test (OGTT)
Measured: 12 weeks of treatment
Insulin OGTT 120 min
Treatment effect on insulin measured at 120 minutes of an oral glucose tolerance test (OGTT)
Measured: 12 weeks of treatment
Fasting Insulin Sensitivity (HOMA-IR)
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.
Measured: 12 weeks of treatment
Matsuda Insulin Sensitivity Index Derived From the OGTT (SI OGTT)
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
Measured: 12 weeks of treatment
Total Cholesterol Levels
Treatment impact on improving total cholesterol levels
Measured: 12 weeks of treatment
High Density Lipoprotein Cholesterol (HDL-C)
Impact of treatment on HDL levels after 12 weeks of treatment
Measured: 12 weeks of treatment
Triglyceride Levels (TRG)
Drug effect of TRG levels after treatment
Measured: 12 weeks of treatment
Low Density Lipoprotein Cholesterol (LDL-C)
Treatment impact on improving LDL-C after treatment
Measured: 12 weeks of treatment
Systolic Blood Pressure
Treatment impact on systolic blood pressure
Measured: 12 weeks of treatment
Diastolic Blood Pressure
Treatment impact on reducing diastolic blood pressure
Measured: 12 weeks of treatment
Menstrual Cycle Frequency
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.
Measured: 12 weeks of treatment
Free Androgen Index (FAI)
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).
Measured: 12 weeks of treatment
Total Testosterone Concentrations (T)
Drug treatment effect on total testosterone concentrations
Measured: 12 weeks of treatment
Sex Hormone Binding Globulin (SHBG)
Drug treatment effect on SHBG
Measured: 12 weeks of treatment
Adrenal Dehydroepiandrosterone Sulfate (DHEAS)
Treatment efficacy in reducing adrenal hyperandrogenism
Measured: 12 weeks of treatment
17(OH)-progesterone
Treatment efficacy in reducing adrenal hyperandrogenism
Measured: 12 weeks of treatment
Androstenedione
Drug treatment effect on androstenedione
Measured: 12 weeks of treatment
Progesterone
Drug treatment effect on progesterone
Measured: 12 weeks of treatment
Luteinizing Hormone (LH)
Drug treatment effect on LH
Measured: 12 weeks of treatment
Follicle Stimulating Hormone (FSH)
Drug treatment effect on FSH
Measured: 12 weeks of treatment
Ovary Volume
Treatment efficacy in reducing ovary volume
Measured: 12 weeks of treatment
Spontaneous Pregnancy Rate
Treatment effect on spontaneous pregnancy rate
Measured: 12 months after treatment
Assisted Reproductive Therapy Pregnancy Rate
Treatment effect on Assisted Reproductive Therapy Pregnancy Rate
Measured: 12 months after treatment
Cumulative Pregnancy Rate
Treatment effect on Cumulative Pregnancy Rate
Measured: 12 months after treatment
Total dosage gonadotropin (GNT)
Drug treatment impact on total dosage GNT
Measured: 12 weeks of treatment
No. of retrieved oocytes/patient
Drug treatment impact on No. of retrieved oocytes/patient
Measured: 12 weeks of treatment
No. of mature (MII) oocytes/patient
Drug treatment impact on No. of mature (MII) oocytes/patient
Measured: 12 weeks of treatment
Fertilization rate
Drug treatment impact on fertilization rate
Measured: 12 weeks of treatment
Oocyte degeneration rate
Drug treatment impact on oocyte degeneration rate
Measured: 12 weeks of treatment
Immaturity rate
Drug treatment impact on immaturity rate
Measured: 12 weeks of treatment
No. of embryos on day 5/patient
Drug treatment impact on No. of embryos on day 5/patient
Measured: 12 weeks of treatment
No. of blastocysts/patient
Drug treatment impact on No. of blastocysts/patient
Measured: 12 weeks of treatment
Blastulation rate
Drug treatment impact on blastulation rate
Measured: 12 weeks of treatment
No. of transferred embryos
Drug treatment impact on No. of transferred embryos
Measured: 12 weeks of treatment
Pregnancy rate per cycle
Drug treatment impact on pregnancy rate per cycle
Measured: 12 weeks of treatment
Pregnancy rate per Embryo Transfer (ET)
Drug treatment impact on pregnancy rate per ET
Measured: 12 weeks of treatment
Implantation rate
Drug treatment impact on implantation rate
Measured: 12 weeks of treatment
No. of cancelled fresh Embryo Transfer (ET) because of hyperstimulation risk
Drug treatment impact on No. of cancelled fresh Embryo Transfer (ET because of hyperstimulation risk
Measured: 12 weeks of treatment
Cryopreservation
Drug treatment impact on cryopreservation
Measured: 12 weeks of treatment
No. of cryopreserved embryos/patient
Drug treatment impact on No. of cryopreserved embryos/patient
Measured: 12 weeks of treatment
Ectopic Pregnancy Rate
Drug treatment impact on Ectopic Pregnancy Rate
Measured: 12 weeks of treatment
Stillbirth Rate
Drug treatment impact on Stillbirth Rate
Measured: 24 months after treatment
Abortion Rate
Drug treatment impact on Abortion Rate
Measured: 24 months after treatment
Gestational Diabetes Mellitus Rate
Drug treatment impact on Gestational Diabetes Mellitus Rate
Measured: 24 months after treatment
Gestational hypertensive disorder (GHD) Rate
Drug treatment impact on Gestational hypertensive disorder (GHD) Rate
Measured: 24 months after treatment
Live Birth Rate
Drug treatment impact on Live Birth Rate
Measured: 24 months after treatment
Gestational age at birth
Drug treatment impact on gestational age at birth
Measured: 24 months after treatment
Type of Delivery Method
Drug treatment impact on Type of Delivery Method
Measured: 24 months after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2023
- Study start1 Nov 2023 (estimated)
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (27)Papers the sponsor has linked to this study.
- Other trials for Polycystic Ovary SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 188 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mỹ Đức Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05952882
- Sponsor's protocol ID
- 08/23/DD-BVMD
- Status last verified
- Oct 2023
- First submitted
- 10 Jul 2023
- Last updated
- 23 Oct 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Rosenfield RL, Ehrmann DA. The Pathogenesis of Polycystic Ovary Syndrome (PCOS): The Hypothesis of PCOS as Functional Ovarian Hyperandrogenism Revisited. Endocr Rev. 2016 Oct;37(5):467-520. doi: 10.1210/er.2015-1104. Epub 2016 Jul 26.
PubMed 27459230Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004 Jan;19(1):41-7. doi: 10.1093/humrep/deh098.
PubMed 14688154Lim SS, Davies MJ, Norman RJ, Moran LJ. Overweight, obesity and central obesity in women with polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update. 2012 Nov-Dec;18(6):618-37. doi: 10.1093/humupd/dms030. Epub 2012 Jul 4.
PubMed 22767467Zeng X, Xie YJ, Liu YT, Long SL, Mo ZC. Polycystic ovarian syndrome: Correlation between hyperandrogenism, insulin resistance and obesity. Clin Chim Acta. 2020 Mar;502:214-221. doi: 10.1016/j.cca.2019.11.003. Epub 2019 Nov 13.
PubMed 31733195Norman RJ, Masters L, Milner CR, Wang JX, Davies MJ. Relative risk of conversion from normoglycaemia to impaired glucose tolerance or non-insulin dependent diabetes mellitus in polycystic ovarian syndrome. Hum Reprod. 2001 Sep;16(9):1995-8. doi: 10.1093/humrep/16.9.1995.
PubMed 11527911Dunaif A, Segal KR, Futterweit W, Dobrjansky A. Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes. 1989 Sep;38(9):1165-74. doi: 10.2337/diab.38.9.1165.
PubMed 2670645Practice Committee of the American Society for Reproductive Medicine. Electronic address: asrm@asrm.org; Practice Committee of the American Society for Reproductive Medicine. Obesity and reproduction: a committee opinion. Fertil Steril. 2021 Nov;116(5):1266-1285. doi: 10.1016/j.fertnstert.2021.08.018. Epub 2021 Sep 25.
PubMed 34583840Zhang J, Liu H, Mao X, Chen Q, Fan Y, Xiao Y, Wang Y, Kuang Y. Effect of body mass index on pregnancy outcomes in a freeze-all policy: an analysis of 22,043 first autologous frozen-thawed embryo transfer cycles in China. BMC Med. 2019 Jun 26;17(1):114. doi: 10.1186/s12916-019-1354-1.
PubMed 31238940Metwally M, Ong KJ, Ledger WL, Li TC. Does high body mass index increase the risk of miscarriage after spontaneous and assisted conception? A meta-analysis of the evidence. Fertil Steril. 2008 Sep;90(3):714-26. doi: 10.1016/j.fertnstert.2007.07.1290. Epub 2008 Feb 6.
PubMed 18068166Panidis D, Farmakiotis D, Rousso D, Kourtis A, Katsikis I, Krassas G. Obesity, weight loss, and the polycystic ovary syndrome: effect of treatment with diet and orlistat for 24 weeks on insulin resistance and androgen levels. Fertil Steril. 2008 Apr;89(4):899-906. doi: 10.1016/j.fertnstert.2007.04.043. Epub 2007 Nov 5.
PubMed 17980364Legro RS, Dodson WC, Kris-Etherton PM, Kunselman AR, Stetter CM, Williams NI, Gnatuk CL, Estes SJ, Fleming J, Allison KC, Sarwer DB, Coutifaris C, Dokras A. Randomized Controlled Trial of Preconception Interventions in Infertile Women With Polycystic Ovary Syndrome. J Clin Endocrinol Metab. 2015 Nov;100(11):4048-58. doi: 10.1210/jc.2015-2778. Epub 2015 Sep 24.
PubMed 26401593Best D, Avenell A, Bhattacharya S. How effective are weight-loss interventions for improving fertility in women and men who are overweight or obese? A systematic review and meta-analysis of the evidence. Hum Reprod Update. 2017 Nov 1;23(6):681-705. doi: 10.1093/humupd/dmx027.
PubMed 28961722Kort JD, Winget C, Kim SH, Lathi RB. A retrospective cohort study to evaluate the impact of meaningful weight loss on fertility outcomes in an overweight population with infertility. Fertil Steril. 2014 May;101(5):1400-3. doi: 10.1016/j.fertnstert.2014.01.036. Epub 2014 Feb 26.
PubMed 24581574Teede HJ, Misso ML, Costello MF, Dokras A, Laven J, Moran L, Piltonen T, Norman RJ; International PCOS Network. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Fertil Steril. 2018 Aug;110(3):364-379. doi: 10.1016/j.fertnstert.2018.05.004. Epub 2018 Jul 19.
PubMed 30033227Legro RS, Arslanian SA, Ehrmann DA, Hoeger KM, Murad MH, Pasquali R, Welt CK; Endocrine Society. Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2013 Dec;98(12):4565-92. doi: 10.1210/jc.2013-2350. Epub 2013 Oct 22.
PubMed 24151290
Study at a glance
From the registry record, last updated by the sponsor on 23 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05952882
- Acronym / sponsor ID
- 08/23/DD-BVMD
- Conditions
- Polycystic Ovary Syndrome, Obesity, Infertility, Female
- Keywords
- Polycystic Ovary Syndrome, GLP-1 agonist, Liraglutide, obesity, weight loss, insulin resistance, androgens, pregnancy rates
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 188 participants (estimated)
- Lead sponsor
- Mỹ Đức HospitalUniversity, hospital or other
- Study start
- 1 Nov 2023 (estimated)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 19 Jul 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LIME 3mg/1500mg | Experimental | Drug: Liraglutide + MetforminMetformin 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 | Active comparator | Drug: MetforminMetformin 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 |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Female gender
- 18-65 years of age
- Diagnosis of polycystic ovary syndrome according to the revised Rotterdam criteria (2003)
- BMI ≥ 27 kg/m2
- Infertility
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Liraglutide + MetforminAlso: LIMEMetformin 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 | Drug | LIME 3mg/1500mg |
| MetforminAlso: METMetformin XR (extended-release) was initiated at 750 mg once daily and increased to 1500 mg once daily after 2 week | Drug | MET 1500mg |
Primary outcome
Absolute Body Weight (BW)
Time frame: 12 weeks of treatment
Treatment impact on change in body weight after 12 weeks of treatment.
Change in Percent Body Weight
Time frame: 12 weeks of treatment
Treatment effect on reducing body weight expressed as percent body weight loss from baseline
58 secondary outcomes
Body Mass Index (BMI)
Time frame: 12 weeks of treatment
Abdominal Adiposity (Waist Circumference [WC])
Time frame: 12 weeks of treatment
Waist-to-Hip Ratio (WHR)
Time frame: 12 weeks of treatment
Waist-to Height Ratio [WHtR]
Time frame: 12 weeks of treatment
Total Fat Mass Evaluated by BIA
Time frame: 12 weeks of treatment
Total Body Fat (%) by BIA (Bioelectrical Impedance Analysis) machine
Time frame: 12 weeks of treatment
Visceral Fat Level (VFL)
Time frame: 12 weeks of treatment
Total lean body mass
Time frame: 12 weeks of treatment
Glucose OGTT 0 min
Time frame: 12 weeks of treatment
Glucose OGTT 120 min
Time frame: 12 weeks of treatment
Insulin OGTT 0 min
Time frame: 12 weeks of treatment
Insulin OGTT 120 min
Time frame: 12 weeks of treatment
Fasting Insulin Sensitivity (HOMA-IR)
Time frame: 12 weeks of treatment
Matsuda Insulin Sensitivity Index Derived From the OGTT (SI OGTT)
Time frame: 12 weeks of treatment
Total Cholesterol Levels
Time frame: 12 weeks of treatment
High Density Lipoprotein Cholesterol (HDL-C)
Time frame: 12 weeks of treatment
Triglyceride Levels (TRG)
Time frame: 12 weeks of treatment
Low Density Lipoprotein Cholesterol (LDL-C)
Time frame: 12 weeks of treatment
Systolic Blood Pressure
Time frame: 12 weeks of treatment
Diastolic Blood Pressure
Time frame: 12 weeks of treatment
Menstrual Cycle Frequency
Time frame: 12 weeks of treatment
Free Androgen Index (FAI)
Time frame: 12 weeks of treatment
Total Testosterone Concentrations (T)
Time frame: 12 weeks of treatment
Sex Hormone Binding Globulin (SHBG)
Time frame: 12 weeks of treatment
Adrenal Dehydroepiandrosterone Sulfate (DHEAS)
Time frame: 12 weeks of treatment
17(OH)-progesterone
Time frame: 12 weeks of treatment
Androstenedione
Time frame: 12 weeks of treatment
Progesterone
Time frame: 12 weeks of treatment
Luteinizing Hormone (LH)
Time frame: 12 weeks of treatment
Follicle Stimulating Hormone (FSH)
Time frame: 12 weeks of treatment
Ovary Volume
Time frame: 12 weeks of treatment
Spontaneous Pregnancy Rate
Time frame: 12 months after treatment
Assisted Reproductive Therapy Pregnancy Rate
Time frame: 12 months after treatment
Cumulative Pregnancy Rate
Time frame: 12 months after treatment
Total dosage gonadotropin (GNT)
Time frame: 12 weeks of treatment
No. of retrieved oocytes/patient
Time frame: 12 weeks of treatment
No. of mature (MII) oocytes/patient
Time frame: 12 weeks of treatment
Fertilization rate
Time frame: 12 weeks of treatment
Oocyte degeneration rate
Time frame: 12 weeks of treatment
Immaturity rate
Time frame: 12 weeks of treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Oct 2023.
- Results publication: PubMed 27459230Rosenfield RL, Ehrmann DA. The Pathogenesis of Polycystic Ovary Syndrome (PCOS): The Hypothesis of PCOS as Functional Ovarian Hyperandrogenism Revisited. Endocr Rev. 2016 Oct;37(5):467-520. doi: 10.1210/er.2015-1104. Epub 2016 Jul 26.
- Results publication: PubMed 14688154Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004 Jan;19(1):41-7. doi: 10.1093/humrep/deh098.
- Results publication: PubMed 22767467Lim SS, Davies MJ, Norman RJ, Moran LJ. Overweight, obesity and central obesity in women with polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update. 2012 Nov-Dec;18(6):618-37. doi: 10.1093/humupd/dms030. Epub 2012 Jul 4.
- Results publication: PubMed 31733195Zeng X, Xie YJ, Liu YT, Long SL, Mo ZC. Polycystic ovarian syndrome: Correlation between hyperandrogenism, insulin resistance and obesity. Clin Chim Acta. 2020 Mar;502:214-221. doi: 10.1016/j.cca.2019.11.003. Epub 2019 Nov 13.
- Results publication: PubMed 11527911Norman RJ, Masters L, Milner CR, Wang JX, Davies MJ. Relative risk of conversion from normoglycaemia to impaired glucose tolerance or non-insulin dependent diabetes mellitus in polycystic ovarian syndrome. Hum Reprod. 2001 Sep;16(9):1995-8. doi: 10.1093/humrep/16.9.1995.
- Results publication: PubMed 2670645Dunaif A, Segal KR, Futterweit W, Dobrjansky A. Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes. 1989 Sep;38(9):1165-74. doi: 10.2337/diab.38.9.1165.
- Results publication: PubMed 34583840Practice Committee of the American Society for Reproductive Medicine. Electronic address: asrm@asrm.org; Practice Committee of the American Society for Reproductive Medicine. Obesity and reproduction: a committee opinion. Fertil Steril. 2021 Nov;116(5):1266-1285. doi: 10.1016/j.fertnstert.2021.08.018. Epub 2021 Sep 25.
- Results publication: PubMed 31238940Zhang J, Liu H, Mao X, Chen Q, Fan Y, Xiao Y, Wang Y, Kuang Y. Effect of body mass index on pregnancy outcomes in a freeze-all policy: an analysis of 22,043 first autologous frozen-thawed embryo transfer cycles in China. BMC Med. 2019 Jun 26;17(1):114. doi: 10.1186/s12916-019-1354-1.
- Results publication: PubMed 18068166Metwally M, Ong KJ, Ledger WL, Li TC. Does high body mass index increase the risk of miscarriage after spontaneous and assisted conception? A meta-analysis of the evidence. Fertil Steril. 2008 Sep;90(3):714-26. doi: 10.1016/j.fertnstert.2007.07.1290. Epub 2008 Feb 6.
- Results publication: PubMed 17980364Panidis D, Farmakiotis D, Rousso D, Kourtis A, Katsikis I, Krassas G. Obesity, weight loss, and the polycystic ovary syndrome: effect of treatment with diet and orlistat for 24 weeks on insulin resistance and androgen levels. Fertil Steril. 2008 Apr;89(4):899-906. doi: 10.1016/j.fertnstert.2007.04.043. Epub 2007 Nov 5.
- Results publication: PubMed 26401593Legro RS, Dodson WC, Kris-Etherton PM, Kunselman AR, Stetter CM, Williams NI, Gnatuk CL, Estes SJ, Fleming J, Allison KC, Sarwer DB, Coutifaris C, Dokras A. Randomized Controlled Trial of Preconception Interventions in Infertile Women With Polycystic Ovary Syndrome. J Clin Endocrinol Metab. 2015 Nov;100(11):4048-58. doi: 10.1210/jc.2015-2778. Epub 2015 Sep 24.
- Results publication: PubMed 28961722Best D, Avenell A, Bhattacharya S. How effective are weight-loss interventions for improving fertility in women and men who are overweight or obese? A systematic review and meta-analysis of the evidence. Hum Reprod Update. 2017 Nov 1;23(6):681-705. doi: 10.1093/humupd/dmx027.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Liraglutide + Metformin and Metformin in people with Polycystic Ovary Syndrome and Obesity, run by Mỹ Đức Hospital.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Absolute Body Weight (BW) (time frame: 12 weeks of treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05952882, which also lists 27 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Oct 2023.