Polycystic Ovary Syndrome (PCOS)Phase 3MET-PCOSNCT07120815
Optimizing Metformin Use in Polycystic Ovary Syndrome
A Phase 3 study testing Metformin 1500 mg daily and Metformin 2250 mg daily in people with Polycystic Ovary Syndrome (PCOS), run by Helsinki University Central Hospital at 1 site in Finland.
Trial summary
The goal of this clinical trial is to learn if a metformin dose of 1500 mg or 2250 mg per day is better to treat polycystic ovary syndrome (PCOS) in adults. It will also learn about the adverse effects of metformin. The trial aims to evaluate which metformin dose is better for: 1. Read more about this study
- Who is it for?
- Ages 18 to 37 years, women only
- Conditions the study is for
- Polycystic Ovary Syndrome (PCOS)
- What is being tested?
- Metformin 1500 mg daily and Metformin 2250 mg daily
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 184 participants
- Where
- 1 siteFinland
- Study dates
- 1 Sep 2025to 31 Dec 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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 37 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Diagnosed PCOS (According to the International evidence-based Guideline for PCOS 2023)
- Age: 18-37 years
- BMI: ≥ 25 and <40 kg/m2
- Signed informed consent and willingness to comply with the trial procedures
- Sufficient skills in the Finnish or Swedish language
Who cannot join
- Not meeting the criteria according to the International evidence-based Guideline for PCOS 2023)
- Use of hormonal contraceptive during the last 3 months
- Pregnancy
- Breastfeeding
- Untreated diabetes
- Hypothyroidism
Show all 19Show fewer
- Hyperprolactinemia
- Use of medications for diabetes,
- Use of medications for high cholesterol
- Use of medications for obesity
- Use of medications for cortisone (per oral)
- Hypersensitivity to metformin
- Acute metabolic acidosis
- Renal impairment
- Hepatic insufficiency
- Heart- or respiratory failure
- Serious mental illness
- Alcoholism
- Investigator site staff directly involved in the conduct of the study and their family members
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Finland1 site
The Reproductive Medicine Unit, Helsinki University Hospital
Helsinki
Johanna M Melin, MD, +358505382526, johanna.melin@hus.fi
About this study
Official title: Optimizing Metformin Use in Polycystic Ovary Syndrome - A Randomized Controlled Trial
The goal of this clinical trial is to learn if a metformin dose of 1500 mg or 2250 mg per day is better to treat polycystic ovary syndrome (PCOS) in adults. It will also learn about the adverse effects of metformin. The trial aims to evaluate which metformin dose is better for:
- improving biochemical and clinical outcomes
- gastrointestinal side-effects
- mental health and quality of life
Participants will:
- Be randomized to take metformin at a dose of either 1500mg or 2250mg every day for 6 months
- Visit the clinic three times during the trial for checkups and tests
- Answer questionnaires on menstrual cyclicity, mental health, quality of life and side-effects
Read the detailed description
INTRODUCTION Polycystic ovary syndrome (PCOS) remains a key public health burden as it is one of the most common endocrine and metabolic disorders affecting up to 13% of women globally. The Rotterdam diagnostic criteria were updated and internationally endorsed in the 2023 International PCOS guideline and include a) ovulatory and menstrual dysfunction, b) biochemical and/or clinical hyperandrogenism and c) polycystic ovary morphology (PCOM) at ultra-sound. For a diagnosis in adults two of three criteria are required, with PCOM remaining nonspecific for PCOS in adolescents.
Women with PCOS present with diverse features; metabolic (weight gain, obesity, insulin resistance and diabetes) reproductive (infertility and pregnancy complications), endocrine (hyperandrogenism, hirsutism and acne) and psychosocial (depression, anxiety and poor quality of life).
While lifestyle management is strongly recommended for weight management, for those with higher body mass index (BMI), sustainable efficacy for weight loss can be limited and additional pharmacological treatment may be needed. The 2023 Updated International PCOS Guideline recommends that metformin, in addition to lifestyle, should be considered in adults with PCOS and BMI ≥ 25 kg/m2 for prevention of weight gain and management of weight and metabolic disorders. Metformin may be considered in adults with BMI < 25 kg/m2 and adolescents with PCOS, acknowledging more limited evidence.
The aim of this randomized controlled trial (RCT) is to evaluate whether a metformin dose of 1500 mg is inferior compared to a dose of 2250 mg per day for females 18-37 years of age with PCOS in:
- improving biochemical and clinical outcomes
- gastrointestinal side-effects
- mental health and quality of life
MATERIALS AND METHODS A double-blind, randomized controlled trial, including adults (age 18-37 years) with PCOS and a BMI ≥ 25 kg/m2 will be carried out. The randomization will be computer-generated and performed by the hospital pharmacy with 1:1 allocation in random blocks. Power analysis has indicated that a total number of 184 females (92 in each group) will be needed to reveal a 4 kg weight reduction (equals 5% weight reduction for a person weighting 80 kg) with an 80% power. We estimated a 15% drop-out in our power analysis.
Potential participants for the study will be recruited from females referred to the Reproductive Medicine Unit at Helsinki University Hospital and by advertising via the patient organization for those with PCOS (Korento). The internationally indorsed Rotterdam criteria will be used to diagnose women with PCOS. Pregnant women, women breastfeeding, women with untreated thyroid disease, hyperprolactinemia, other conditions with hyperandrogenism or use of hormonal contraceptive during the last three months will be excluded.
Women willing to participate in the study will be randomized to metformin 1500mg or 2250 mg per day for a 6-month period. Blood samples (on hyperandrogenism and metabolism), clinical examination (anthropometry and hirsutism) and a questionnaire (menstrual cyclicity, mental health, quality of life, side-effects) will be performed before starting the metformin medication, as well as at 3 and 6 months after onset of medication. Polycystic ovary morphology will be evaluated by measuring anti-mullerian hormone levels (AMH) and by vaginal ultrasound.
- Conditions
- Polycystic Ovary Syndrome (PCOS)
- Being tested
- Metformin 1500 mg daily, Metformin 2250 mg daily
- Keywords
- polycystic ovary syndrome, metformin, randomized controlled trial
- Medical subject headings
- Polycystic Ovary Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metformin 1500 mg dailyDrug
metformin 500mg tablets, 3 times per day
Metformin 2250 mg dailyDrug
Metformin 750mg, 3 times daily
| Study group | Role | What they receive |
|---|---|---|
| Women 18-37 years old with a BMI ≥ 25 kg/m2, metformin 2250mg per day | Active comparator | metformin tablets 2250 mg per day Receives: Drug: Metformin 2250 mg daily |
| Women 18-37 years old with a BMI ≥ 25 kg/m2, metformin 1500mg per day | Experimental | metformin tablets 1500 mg per day Receives: Drug: Metformin 1500 mg daily |
What is being measured
The primary outcome is the main question the study is designed to answer.
Weight
Weight will be measured by a standard scale to an accuracy of +/- 0,1kg.
Measured: The investigators will measure change in outcomes from baseline to 14 and 26 weeks
Homeostatic model assessment for insulin resistance (HOMA-IR)
HOMA-IR will be calculated with the formula: fasting plasma glucose (mmol/L) × fasting serum insulin (mU/L) divided by 22.5 (9)
Measured: The investigators will measure change in outcomes from baseline to 14 and 26 weeks
Hirsutism
Modified Ferriman Gallwey score (mFG) will be measured and a score of 4 or more will be regarded as hirsutism in Caucasian women, whereas a score of 6 or more will be regarded hirsutism for other ethnicities
Measured: The investigators will report change from baseline to 14 and 26 weeks.
Total testosterone
Testosterone nmol/l (liquid chromatography with tandem mass spectrometry (LC-MS/MS). All laboratory tests will be taken in the morning, between 7-10 am, after 12 hours fasting.
Measured: The investigators will measure change from baseline to 14 and 26 weeks
Appearance of severe of adverse effects
In our questionnaire the investigators will ask the participants whether they have experienced abdominal pain, reflux, nausea, diarrhoea or loss of appetite during the last two weeks and grade the symptoms from 1-5 (1 being never and 5 being all the time). The investigators will count the scores and give each participant a score between 5-25. A severe adverse effect is defined as a score of 4 or more in one of the questions (indicating a daily experience of abdominal pain, reflux, nausea, diarrhoea or loss of appetite during the last two weeks).
Measured: The investigators will measure change from baseline to 14 and 26 weeks
Anti-Mullerian hormone (AMH)
AMH will be measured in ug/l. All laboratory tests will be taken in the morning, between 7-10 am, after 12 hours fasting.
Measured: The investigators will measure change from baseline to 14 and 26 weeks
Secondary outcomes (32)
Body mass index (BMI)
Weight (kilogram) and height (metre) will be combined to report BMI in kg/m^2
Measured: The investigators will measure change in outcomes from baseline to 14 and 26 weeks
Waist circumference (WC)
WC will be measured halfway between the participant's lowest rib and the top of the participant's hipbone
Measured: The investigators will measure change in outcomes from baseline to 14 and 26 weeks
Waist-hip-ratio (WHR)
WHR will be calculated as waist measurement divided by hip measurement (W⁄H). Hip circumference is determined as the maximum value over the glottal region, measured to the nearest centimetre.
Measured: The investigators will measure change in outcomes from baseline to 14 and 26 weeks
Body adiposity index (BAI)
BAI will be measured using the following equation: hip circumference (cm)/height (m) - 18
Measured: The investigators will measure change in outcomes from baseline to 14 and 26 weeks
Body composition
Body composition will be measured with a multi-frequency segmental body composition analyzer (TANITA Health Ware) WHR (Waist-hip-ratio). Will be calculated as waist measurement divided by hip measurement (W⁄H). Hip circumference is determined as the maximum value over the glottal region, measured to the nearest centimetre.
WC (Waist circumference). Measured halfway between the participant's lowest rib and the top of the participant's hipbone BAI (Body adiposity index). Will be measured using the following equation: hip circumference (cm)/height (m) - 18 BP (blood pressure) (systolic and diastolic) and pulse. Will be measured twice with at least 3 minutes apart after at least 10 min rest from non-dominant upper extremity in a subject in supine position
Measured: The investigators will measure change in outcomes from baseline to 14 and 26 weeks
Blood pressure (BP)
BP (systolic and diastolic) will be measured twice with at least 3 minutes apart after at least 10 min rest from non-dominant upper extremity in a subject in supine position
Measured: The investigators will measure change in outcomes from baseline to 14 and 26 weeks
Pulse
Pulse will be measured twice with at least 3 minutes apart after at least 10 min rest from non-dominant upper extremity in a subject in supine position
Measured: The investigators will measure change in outcomes from baseline to 14 and 26 weeks
Fasting glucose
fasting glucose mmol/l (photometric hexokinase method) All laboratory tests will be taken in the morning, between 7-10 am, after 12 hours fasting.
Measured: The investigators will measure change in outcomes from baseline to 14 and 26 weeks
Fasting insulin
fasting insulin mU/l (immunochemiluminometric assay) All laboratory tests will be taken in the morning, between 7-10 am, after 12 hours fasting.
Measured: The investigators will measure change in outcomes from baseline to 14 and 26 weeks
HbA1C
HbA1C mmol/mol (photometric enzymatic method) All laboratory tests will be taken in the morning, between 7-10 am, after 12 hours fasting.
Measured: The investigators will measure change in outcomes from baseline to 14 and 26 weeks
Lipids (cholesterol and its subclasses, triglycerides)
Total cholesterol, mmol/l and triglycerides mmol/l with an enzymatic photometric method, LDL and HDL mmol/l with a direct enzymatic photometric method All laboratory tests will be taken in the morning, between 7-10 am, after 12 hours fasting.
Measured: The investigators will measure change in outcomes from baseline to 14 and 26 weeks
C-reactive protein (CRP)
CRP will be measured in mg/l (photometric immunochemical method) All laboratory tests will be taken in the morning, between 7-10 am, after 12 hours fasting.
Measured: The investigators will measure change in outcomes from baseline to 14 and 26 weeks
2-hour oral glucose tolerance test (OGTT)
2-hour OGTT mmol/l
Measured: The investigators will measure change in outcomes from baseline to 14 and 26 weeks
Alanine Aminotransferase (ALAT)
ALAT will be measured in U/l (photometric method according to the International Federation of Clinical Chemistry and Laboratory Medicine recommendation) All laboratory tests will be taken in the morning, between 7-10 am, after 12 hours fasting.
Measured: The investigators will measure change in outcomes from baseline to 14 and 26 weeks
Gamma-glutamyl transferase (G-GT)
G-GT will be measured in U/l (photometric method according to the International Federation of Clinical Chemistry and Laboratory Medicine recommendation) All laboratory tests will be taken in the morning, between 7-10 am, after 12 hours fasting.
Measured: The investigators will measure change in outcomes from baseline to 14 and 26 weeks
Fatty Liver Index (FLI)
FLI will be measured by the following formula:
FLI = (e^y) / (1 + e^y) * 100 where: y = 0.953 * ln(TG) + 0.139 * BMI + 0.718 * ln(GGT) + 0.053 * WC - 15.745 e is the base of the natural logarithm (approximately 2.718) ln denotes the natural logarithm TG is triglycerides in mg/dL BMI is body mass index in kg/m² GGT is gamma-glutamyltransferase in U/L WC is waist circumference in cm All laboratory tests will be taken in the morning, between 7-10 am, after 12 hours fasting.
Measured: The investigators will measure change in outcomes from baseline to 14 and 26 weeks
Matsuda Index
Matsuda Index will be measured by the following formula:
Matsuda Index = 10,000 / √[(fasting glucose (mg/dL) * fasting insulin (µU/mL)) * (mean glucose (mg/dL) * mean insulin (µU/mL) during OGTT) All laboratory tests will be taken in the morning, between 7-10 am, after 12 hours fasting.
Measured: The investigators will measure change in outcomes from baseline to 14 and 26 weeks
Triglyceride-Glucose (TyG) index
TyG Index will be measured by the following formula:
TyG Index=fasting triglycerides (mg/dL) * fasting glucose (mg/dL) / 2 All laboratory tests will be taken in the morning, between 7-10 am, after 12 hours fasting.
Measured: The investigators will measure change in outcomes from baseline to 14 and 26 weeks
Acne
The investigators will use the PCOS-Q to ask about acne (score 1-7)
Measured: The investigators will report change from baseline to 14 and 26 weeks
Alopecia
The investigators will use the PCOS-Q to ask about alopecia (score 1-7)
Measured: The investigators will report change from baseline to 14 and 26 weeks
Free androgen index (FAI)
FAI will be calculated with the following formula:
FAI = 100 X ((Total Testosterone (nmol/L)/SHBG (nmol/L)) All laboratory tests will be taken in the morning, between 7-10 am, after 12 hours fasting.
Measured: The investigators will measure change from baseline to 14 and 26 weeks
Sex hormone binding globulin (SHBG)
SHBG will be measured in nmol/l (immunochemiluminometric assay) All laboratory tests will be taken in the morning, between 7-10 am, after 12 hours fasting.
Measured: The investigators will measure change from baseline to 14 and 26 weeks
Dehydroepiandrosterone sulfate (DHEAS)
DHEAS will be measured in nmol/l (immunochemiluminometric assay) All laboratory tests will be taken in the morning, between 7-10 am, after 12 hours fasting.
Measured: The investigators will measure change from baseline to 14 and 26 weeks
Androstenedione
Androstenedione will be measured in nmol/l (liquid chromatography with tandem mass spectrometry (LC-MS/MS) All laboratory tests will be taken in the morning, between 7-10 am, after 12 hours fasting.
Measured: The investigators will measure change from baseline to 14 and 26 weeks
Free testosterone
Free calculated testosterone will be measured in pmol/l (by Anderson Formula). All laboratory tests will be taken in the morning, between 7-10 am, after 12 hours fasting.
Measured: The investigators will measure change from baseline to 14 and 26 weeks
Menstrual regularity
Questionnaire, where asking if the menstrual cycle is regular (defined as 21 days or more but under 36 days)
Measured: The investigators will measure change from baseline to 14 and 26 weeks
Menstrual cycle length
Questionnaire, where asking how long the two previous cycles were (days)
Measured: The investigators will measure change from baseline to 14 and 26 weeks
Appearance of gastrointestinal adverse effects (GI AE)
In our questionnaire the investigators will ask the participants whether they have experienced abdominal pain, reflux, nausea, diarrhoea or loss of appetite during the last two weeks and grade the symptoms from 1-5 (1 being never and 5 being all the time). The investigators will count the scores and give each participant a score between 5-25. A severe adverse effect is defined as a score of 4 or more in one of the questions (indicating a daily experience of abdominal pain, reflux, nausea, diarrhoea or loss of appetite during the last two weeks).
Measured: The investigators will measure change from baseline to 14 and 26 weeks
Quality of life (QoL)
The PCOS-Q is a questionnaire that was specifically designed to measure quality of life for women with PCOS. Questions on depression, anxiety, fear etc will be given scores from 1-7, depending on severity.
Measured: The investigators will measure change from baseline to 14 and 26 weeks
Weight stigma
In the questionnaire appearance of weight stigma and examples on it will be asked.
Measured: The investigators will measure change from baseline to 14 and 26 weeks
Follicle number per ovary (FNPO) and antral follicle count (AFC)
Vaginal ultrasound where the investigators measure FNPO and AFC will be performed at any stage of the cycle.
Measured: The investigators will measure change from baseline to 14 and 26 weeks.
Ovarian volume
Vaginal ultrasound where the investigators measure ovarian volume will be performed at any stage of the cycle.
Measured: The investigators will measure change from baseline to 14 and 26 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2025
- Study start1 Sep 2025 (estimated)
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Polycystic Ovary Syndrome (PCOS)Studies of the same condition, open and under way.
- More trials run by Helsinki University Central HospitalThe sponsor's other registered studies.
- 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 184 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Helsinki University Central Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Valtion tutkimusraha (funding), Sakari Alhopuro foundation (funding), The Medical Society of Finland (funding)
- Responsible party
- Principal investigator, Johanna Melin, Helsinki University Central Hospital
- Investigators
- Johanna M Melin, MD, Principal investigator, The Reproductive Medicine Unit, Helsinki University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07120815
- Sponsor's protocol ID
- HUS8428/TYH2024323
- Other IDs
- 2023-509259-15-01, 2023
- Acronym
- MET-PCOS
- Status last verified
- Aug 2025
- First submitted
- 9 Jul 2025
- Last updated
- 13 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified participant-level data, including demographic information, medical history, laboratory results, and outcome data, will be shared. A data dictionary detailing variable names and coding will also be provided.
Publications
Hautamaki HM, Savolainen-Peltonen H, Rono K, Melin J. Optimising metformin use in polycystic ovary syndrome (MET-PCOS): study protocol for a double-blind randomised controlled trial. BMJ Open. 2026 Mar 12;16(3):e115656. doi: 10.1136/bmjopen-2025-115656.
PubMed 41819580
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimizing Metformin Use in Polycystic Ovary Syndrome - A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT07120815
- Acronym / sponsor ID
- MET-PCOS / HUS8428/TYH2024323
- Conditions
- Polycystic Ovary Syndrome (PCOS)
- Keywords
- polycystic ovary syndrome, metformin, randomized controlled trial
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 184 participants (estimated)
- Lead sponsor
- Helsinki University Central HospitalUniversity, hospital or other
- Collaborators
- Valtion tutkimusraha (funding), Sakari Alhopuro foundation (funding), The Medical Society of Finland (funding)
- Study start
- 1 Sep 2025 (estimated)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 13 Aug 2025 (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.
The goal of this clinical trial is to learn if a metformin dose of 1500 mg or 2250 mg per day is better to treat polycystic ovary syndrome (PCOS) in adults. It will also learn about the adverse effects of metformin. The trial aims to evaluate which metformin dose is better for:
- improving biochemical and clinical outcomes
- gastrointestinal side-effects
- mental health and quality of life
Participants will:
- Be randomized to take metformin at a dose of either 1500mg or 2250mg every day for 6 months
- Visit the clinic three times during the trial for checkups and tests
- Answer questionnaires on menstrual cyclicity, mental health, quality of life and side-effects
Detailed description
INTRODUCTION Polycystic ovary syndrome (PCOS) remains a key public health burden as it is one of the most common endocrine and metabolic disorders affecting up to 13% of women globally. The Rotterdam diagnostic criteria were updated and internationally endorsed in the 2023 International PCOS guideline and include a) ovulatory and menstrual dysfunction, b) biochemical and/or clinical hyperandrogenism and c) polycystic ovary morphology (PCOM) at ultra-sound. For a diagnosis in adults two of three criteria are required, with PCOM remaining nonspecific for PCOS in adolescents.
Women with PCOS present with diverse features; metabolic (weight gain, obesity, insulin resistance and diabetes) reproductive (infertility and pregnancy complications), endocrine (hyperandrogenism, hirsutism and acne) and psychosocial (depression, anxiety and poor quality of life).
While lifestyle management is strongly recommended for weight management, for those with higher body mass index (BMI), sustainable efficacy for weight loss can be limited and additional pharmacological treatment may be needed. The 2023 Updated International PCOS Guideline recommends that metformin, in addition to lifestyle, should be considered in adults with PCOS and BMI ≥ 25 kg/m2 for prevention of weight gain and management of weight and metabolic disorders. Metformin may be considered in adults with BMI < 25 kg/m2 and adolescents with PCOS, acknowledging more limited evidence.
The aim of this randomized controlled trial (RCT) is to evaluate whether a metformin dose of 1500 mg is inferior compared to a dose of 2250 mg per day for females 18-37 years of age with PCOS in:
- improving biochemical and clinical outcomes
- gastrointestinal side-effects
- mental health and quality of life
MATERIALS AND METHODS A double-blind, randomized controlled trial, including adults (age 18-37 years) with PCOS and a BMI ≥ 25 kg/m2 will be carried out. The randomization will be computer-generated and performed by the hospital pharmacy with 1:1 allocation in random blocks. Power analysis has indicated that a total number of 184 females (92 in each group) will be needed to reveal a 4 kg weight reduction (equals 5% weight reduction for a person weighting 80 kg) with an 80% power. We estimated a 15% drop-out in our power analysis.
Potential participants for the study will be recruited from females referred to the Reproductive Medicine Unit at Helsinki University Hospital and by advertising via the patient organization for those with PCOS (Korento). The internationally indorsed Rotterdam criteria will be used to diagnose women with PCOS. Pregnant women, women breastfeeding, women with untreated thyroid disease, hyperprolactinemia, other conditions with hyperandrogenism or use of hormonal contraceptive during the last three months will be excluded.
Women willing to participate in the study will be randomized to metformin 1500mg or 2250 mg per day for a 6-month period. Blood samples (on hyperandrogenism and metabolism), clinical examination (anthropometry and hirsutism) and a questionnaire (menstrual cyclicity, mental health, quality of life, side-effects) will be performed before starting the metformin medication, as well as at 3 and 6 months after onset of medication. Polycystic ovary morphology will be evaluated by measuring anti-mullerian hormone levels (AMH) and by vaginal ultrasound.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Women 18-37 years old with a BMI ≥ 25 kg/m2, metformin 2250mg per day | Active comparator | Drug: Metformin 2250 mg dailymetformin tablets 2250 mg per day |
| Women 18-37 years old with a BMI ≥ 25 kg/m2, metformin 1500mg per day | Experimental | Drug: Metformin 1500 mg dailymetformin tablets 1500 mg per day |
Who may qualify
- Ages
- 18 to 37 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Diagnosed PCOS (According to the International evidence-based Guideline for PCOS 2023)
- Age: 18-37 years
- BMI: ≥ 25 and <40 kg/m2
- Signed informed consent and willingness to comply with the trial procedures
- Sufficient skills in the Finnish or Swedish language
Key exclusion criteria (19 listed)
- Not meeting the criteria according to the International evidence-based Guideline for PCOS 2023)
- Use of hormonal contraceptive during the last 3 months
- Pregnancy
- Breastfeeding
- Untreated diabetes
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 |
|---|---|---|
| Metformin 1500 mg dailymetformin 500mg tablets, 3 times per day | Drug | Women 18-37 years old with a BMI ≥ 25 kg/m2, metformin 1500mg per day |
| Metformin 2250 mg dailyMetformin 750mg, 3 times daily | Drug | Women 18-37 years old with a BMI ≥ 25 kg/m2, metformin 2250mg per day |
Primary outcome
Weight
Time frame: The investigators will measure change in outcomes from baseline to 14 and 26 weeks
Weight will be measured by a standard scale to an accuracy of +/- 0,1kg.
Homeostatic model assessment for insulin resistance (HOMA-IR)
Time frame: The investigators will measure change in outcomes from baseline to 14 and 26 weeks
HOMA-IR will be calculated with the formula: fasting plasma glucose (mmol/L) × fasting serum insulin (mU/L) divided by 22.5 (9)
Hirsutism
Time frame: The investigators will report change from baseline to 14 and 26 weeks.
Modified Ferriman Gallwey score (mFG) will be measured and a score of 4 or more will be regarded as hirsutism in Caucasian women, whereas a score of 6 or more will be regarded hirsutism for other ethnicities
Total testosterone
Time frame: The investigators will measure change from baseline to 14 and 26 weeks
Testosterone nmol/l (liquid chromatography with tandem mass spectrometry (LC-MS/MS). All laboratory tests will be taken in the morning, between 7-10 am, after 12 hours fasting.
Appearance of severe of adverse effects
Time frame: The investigators will measure change from baseline to 14 and 26 weeks
In our questionnaire the investigators will ask the participants whether they have experienced abdominal pain, reflux, nausea, diarrhoea or loss of appetite during the last two weeks and grade the symptoms from 1-5 (1 being never and 5 being all the time). The investigators will count the scores and give each participant a score between 5-25. A severe adverse effect is defined as a score of 4 or more in one of the questions (indicating a daily experience of abdominal pain, reflux, nausea, diarrhoea or loss of appetite during the last two weeks).
Anti-Mullerian hormone (AMH)
Time frame: The investigators will measure change from baseline to 14 and 26 weeks
AMH will be measured in ug/l. All laboratory tests will be taken in the morning, between 7-10 am, after 12 hours fasting.
32 secondary outcomes
Body mass index (BMI)
Time frame: The investigators will measure change in outcomes from baseline to 14 and 26 weeks
Waist circumference (WC)
Time frame: The investigators will measure change in outcomes from baseline to 14 and 26 weeks
Waist-hip-ratio (WHR)
Time frame: The investigators will measure change in outcomes from baseline to 14 and 26 weeks
Body adiposity index (BAI)
Time frame: The investigators will measure change in outcomes from baseline to 14 and 26 weeks
Body composition
Time frame: The investigators will measure change in outcomes from baseline to 14 and 26 weeks
Blood pressure (BP)
Time frame: The investigators will measure change in outcomes from baseline to 14 and 26 weeks
Pulse
Time frame: The investigators will measure change in outcomes from baseline to 14 and 26 weeks
Fasting glucose
Time frame: The investigators will measure change in outcomes from baseline to 14 and 26 weeks
Fasting insulin
Time frame: The investigators will measure change in outcomes from baseline to 14 and 26 weeks
HbA1C
Time frame: The investigators will measure change in outcomes from baseline to 14 and 26 weeks
Lipids (cholesterol and its subclasses, triglycerides)
Time frame: The investigators will measure change in outcomes from baseline to 14 and 26 weeks
C-reactive protein (CRP)
Time frame: The investigators will measure change in outcomes from baseline to 14 and 26 weeks
2-hour oral glucose tolerance test (OGTT)
Time frame: The investigators will measure change in outcomes from baseline to 14 and 26 weeks
Alanine Aminotransferase (ALAT)
Time frame: The investigators will measure change in outcomes from baseline to 14 and 26 weeks
Gamma-glutamyl transferase (G-GT)
Time frame: The investigators will measure change in outcomes from baseline to 14 and 26 weeks
Fatty Liver Index (FLI)
Time frame: The investigators will measure change in outcomes from baseline to 14 and 26 weeks
Matsuda Index
Time frame: The investigators will measure change in outcomes from baseline to 14 and 26 weeks
Triglyceride-Glucose (TyG) index
Time frame: The investigators will measure change in outcomes from baseline to 14 and 26 weeks
Acne
Time frame: The investigators will report change from baseline to 14 and 26 weeks
Alopecia
Time frame: The investigators will report change from baseline to 14 and 26 weeks
Free androgen index (FAI)
Time frame: The investigators will measure change from baseline to 14 and 26 weeks
Sex hormone binding globulin (SHBG)
Time frame: The investigators will measure change from baseline to 14 and 26 weeks
Dehydroepiandrosterone sulfate (DHEAS)
Time frame: The investigators will measure change from baseline to 14 and 26 weeks
Androstenedione
Time frame: The investigators will measure change from baseline to 14 and 26 weeks
Free testosterone
Time frame: The investigators will measure change from baseline to 14 and 26 weeks
Menstrual regularity
Time frame: The investigators will measure change from baseline to 14 and 26 weeks
Menstrual cycle length
Time frame: The investigators will measure change from baseline to 14 and 26 weeks
Appearance of gastrointestinal adverse effects (GI AE)
Time frame: The investigators will measure change from baseline to 14 and 26 weeks
Quality of life (QoL)
Time frame: The investigators will measure change from baseline to 14 and 26 weeks
Weight stigma
Time frame: The investigators will measure change from baseline to 14 and 26 weeks
Follicle number per ovary (FNPO) and antral follicle count (AFC)
Time frame: The investigators will measure change from baseline to 14 and 26 weeks.
Ovarian volume
Time frame: The investigators will measure change from baseline to 14 and 26 weeks.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2025.
- Derived from this study: PubMed 41819580Hautamaki HM, Savolainen-Peltonen H, Rono K, Melin J. Optimising metformin use in polycystic ovary syndrome (MET-PCOS): study protocol for a double-blind randomised controlled trial. BMJ Open. 2026 Mar 12;16(3):e115656. doi: 10.1136/bmjopen-2025-115656.
- Individual participant dataSharing planned: Yes. De-identified participant-level data, including demographic information, medical history, laboratory results, and outcome data, will be shared. A data dictionary detailing variable names and coding will also be provided.
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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.
Johanna M Melin, MD principal investigator
The Reproductive Medicine Unit, Helsinki University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Metformin 1500 mg daily and Metformin 2250 mg daily in people with Polycystic Ovary Syndrome (PCOS), run by Helsinki University Central Hospital at 1 site in Finland.
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 5 inclusion and 19 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: opening soon, as of the sponsor's last update on 13 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Finland. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Johanna M Melin, MD (+358505382526, johanna.melin@hus.fi), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Weight (time frame: The investigators will measure change in outcomes from baseline to 14 and 26 weeks). The study lists 6 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 NCT07120815, which also lists 1 linked publication.
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 13 Aug 2025.