A Phase 2/3 interventional study of Metformin and Semaglutide Injectable Product in Polycystic Ovary Syndrome, sponsored by University of Hull. Not yet recruiting at 1 site in United Kingdom. Open to female participants aged 18 Years to 45 Years. Per ClinicalTrials.gov, last updated 2024-05-10.
Sponsored by University of Hull · Phase 2/3, Interventional, and Treatment
The goal of this clinical trial is to compare the effect of Semaglutide and metformin on weight loss in obese women with Polycystic Ovarian Syndrome (PCOS) over a 28-week treatment period.
The main question it aims to answer is:
Participants will be divided into 2 groups by chance. In the first group, participants will be asked to take metformin orally. In the second group, participants will take Semaglutide by injection under the skin weekly.
The maximum duration of participation for the patients in the trial is 32 weeks.
Researchers will compare the weight reduction, quality of life and individuals' wellbeing between the two groups.
Background:
Polycystic ovary syndrome (PCOS) is one of the most common metabolic disorders that affects 6-20% of reproductive-aged women and has an increased risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease. Obesity affects more than 50% of women with PCOS and has been demonstrated to play a vital role in the establishment of symptoms in these patients. Bariatric surgery has been shown to improve metabolic parameters but reports of dietary intervention studies have been variable. PCOS is associated with an increased risk of depressive symptoms and a low quality of life (QOL) with weight being a major contributor. Even modest weight loss of 5% of initial body weight has been shown to improve menstrual disturbance, testosterone levels, hyperlipidaemia, and insulin resistance in women with PCOS. Metformin, most commonly used medication for PCOS works by improving insulin sensitivity in peripheral tissues, inhibit hepatic glucose production and increase glucose disposal by the peripheral tissues.
It has been used for decades in treatment of PCOS with improvement in menstrual irregularities and possible reduction of androgen levels. However, the effect of metformin on body weight (a major contributor of pathophysiology and symptoms in PCOS) remained highly variable between these patients. The first observational study of metformin in PCOS reported weight loss during metformin therapy. In a randomised controlled trial (RCT) designed to investigate the effect of metformin in body weight reported a significant decrease in BMI in obese women independent of their lifestyle. The recent meta-analysis assessed the effectiveness of metformin in PCOS reported a significant effect on body mass index (BMI) in women with PCOS. It is clear, however, that metformin does not increase body weight and might help to limit weight gain. Along with wide variation in response metformin is not tolerated by 10-20% of women with PCOS mainly due to its gastrointestinal side effects. Therefore, it is imperative that investigators look beyond metformin in obese women with PCOS, as this has shown to improve metabolic and hormonal parameters.
In a pilot study, another glucagon like peptide - 1 receptor agonist (GLP-1RA), liraglutide 1.8mg daily for 6 months reduced weight in obese women with PCOS and age and body mass index matched control women. They also demonstrated that liraglutide 1.8mg daily for 6 months in young obese women with PCOS showed significant improvement in physical health, social health, psychological and hence quality of life in this group.
Semaglutide a new GLP-1RA approved as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes and is associated with significant weight loss. In patients with type 2 diabetes, there was ≥5% weight loss in 63% of patients treated with Semaglutide. On the other hand, liraglutide has shown around 5-7 kg of weight reduction from the baseline in patient with T2DM. However, it has been previously reported in the SUSTAIN trials, Semaglutide-treated subjects have achieved a significant weight loss of >10% compared to placebo. The effect of Semaglutide on weight loss and resultant improvement in the metabolic parameters and QOL in women with PCOS is unknown. In a recent double-blind randomized trial, compared Semaglutide to liraglutide in obese patients with no diabetes has shown a significant weight loss compared to placebo. Liraglutide is administered as a daily subcutaneous injection whereas Semaglutide is administered as a weekly subcutaneous injection. Therefore, investigators are conducting this trial to assess the feasibility and trying to replicate the greater weight loss with Semaglutide that has already been shown in other trial, in obese women with PCOS.
Overall hypothesis:
Treatment with Semaglutide will result in significant weight loss compared to metformin and that will be associated with significant improvements in hormonal and metabolic parameters, quality of life and cardiovascular risk factors as secondary endpoints in obese women with PCOS.
This is a randomized controlled trial
The trial consists of 7 visits and 3 telephone calls. Patients will be randomized on a 1:1 ratio to receive either:
Semaglutide 0.25mg subcutaneous weekly for 4 weeks followed by semaglutide 0.5 mg weekly for 4 weeks, then escalating to semaglutide 1 mg/ week for 4 weeks, followed by semaglutide 1.7 mg/week for 4 weeks before titrated up to maximum dose of 2.4 mg a week for 12 weeks if tolerated.
Or Metformin 500 mg/ day for 1 week followed by 500mg/twice a day for 1 week titrated up to 500 mg / day with breakfast and 1000 mg/ day with evening meals for 26 weeks if tolerated.
956 studies on the registry are indexed under Polycystic Ovary Syndrome; 176 are open to participants now.
This study's planned enrollment of 60 is below the median of 70 across 697 interventional studies indexed under Polycystic Ovary Syndrome.
Browse Polycystic Ovary Syndrome studies →University of Hull is the lead sponsor of 35 studies on the registry; 7 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Subjects who are on any of the following medications within 3 months of screening:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants in this group will be given metformin
Drug: Metformin
Participants in this group with receive Semaglutide
Drug: Semaglutide Injectable Product
Participants will receive metformin
Participants in this group will receive injectable Semaglutide
Weight loss (kg)
Changes in weight from baseline
Time frame: 28 weeks
Fat mass
Changes in body fat percentage (%) measured using TANITA
Time frame: 28 weeks
Free androgen index (FAI)
Changes in Free androgen index (%) calculated from testosterone and sex hormone binding globulin; FAI= (Total Testosterone/Sex Hormone binding globulin)X100%
Time frame: 28 weeks
Blood pressure
Changes in blood pressure (mmHg)
Time frame: 28 weeks
Pulse rate
Changes in pulse rate (beats per minute)
Time frame: 28 weeks
Glucose tolerance
Changes in glucose reading (mmol/l) at 2 hours following 75g of oral glucose
Time frame: 28 weeks
Plan to share: No
Start is estimated for Mar 2025; primary completion for Sep 2025, 6 months later.
Of 13 phase 2/3 interventional studies under Polycystic Ovary Syndrome, half reached primary completion within 12 months of starting (the median); a quarter within 8 and three quarters within 26. This study's planned 6 months is below that.
How these figures are worked out, and which studies are left out of them.
This study is not yet recruiting, as verified in May 2024. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Semaglutide
University of Hull