A Randomized Controlled Trial Evaluating Metformin and Metformin Hydrochloride Dosing in Overweight Adults with Polycystic Ovary Syndrome

The primary objective of this study is to determine if a **metformin** dose of 1500 mg is inferior to a dose of 2250 mg per day in terms of biochemical and clinical outcomes in overweight individuals aged 18-37 years with **polycystic ovary syndrome** (PCOS). This is clinically relevant as optimizing the dosage of metformin could enhance therapeutic efficacy while minimizing potential side effects, thereby improving patient management in PCOS.

Secondary objectives include evaluating whether a metformin dose of 1500 mg is inferior to a dose of 2250 mg per day concerning gastrointestinal side effects and psychological well-being in the same population. These aspects are crucial for assessing the overall tolerability and quality of life impacts associated with different dosing regimens of metformin in PCOS management.

The clinical trial focuses on evaluating the efficacy of different doses of metformin in women diagnosed with **polycystic ovary syndrome** (PCOS). The study population comprises females aged 18 to 37 years, all of whom have been diagnosed with PCOS according to the updated 2023 International PCOS guideline. Participants are required to have a body mass index (BMI) ranging from 25 kg/m² to less than 40 kg/m², indicating an overweight status. The trial does not include male subjects or any vulnerable populations. Participants were selected based on their willingness to comply with trial procedures and provide informed consent. The sponsor has not provided information regarding the total number of participants. Lifestyle factors such as diet and physical activity are not specified, but the inclusion criteria ensure a focus on a specific demographic with a defined health condition.

The clinical trial is designed to evaluate the efficacy of two different doses of **metformin** in the management of polycystic ovary syndrome (PCOS) in overweight women aged 18-37 years. This study is a randomized, controlled trial with a double-blind design to ensure unbiased results. The trial aims to determine whether a daily dose of 1500 mg of metformin is inferior to a 2250 mg dose in terms of biochemical and clinical outcomes. The trial is expected to commence recruitment on December 1, 2024, and conclude by July 31, 2034, with a maximum treatment period of 48 weeks for each participant.

Participants will undergo a series of study visits, beginning with an inclusion visit where eligibility will be confirmed based on criteria such as age, PCOS diagnosis according to the 2023 International PCOS guideline, and a body mass index (BMI) between 25 and 40 kg/m². Informed consent will be obtained at this stage. Follow-up visits will be scheduled to monitor primary endpoints, including anthropometrics, androgenicity, metabolic parameters, and gastrointestinal side effects. Secondary endpoints will also be assessed, such as menstrual cyclicity, quality of life, and additional metabolic and anthropometric measures. The end-of-study visit will evaluate the overall outcomes and any adverse effects experienced during the trial.

Participant involvement is expected to last up to 48 weeks, with conditions for early termination including non-compliance with trial procedures or the occurrence of significant adverse events. The trial will utilize oral administration of metformin, with a maximum daily dose of 2500 mg. The study will adhere to rigorous scientific standards to ensure the reliability and validity of the findings, contributing valuable insights into the optimal dosing of metformin for PCOS management.

The clinical trial involves the administration of **METFORMIN**, a **coated tablet** formulation, as the experimental medication. The active substance in this formulation is **metformin hydrochloride**, a chemical compound. The maximum daily dose of METFORMIN is 2500 mg, administered orally. The treatment period extends up to 48 weeks. The trial aims to evaluate the efficacy of a 1500 mg daily dose compared to a 2250 mg daily dose in overweight individuals aged 18-37 years with polycystic ovary syndrome (PCOS). The dosing schedule is designed to ensure participant compliance, with regular monitoring to assess adherence to the prescribed regimen.

Additionally, the study includes the use of **METFORMIN HYDROCHLORIDE** in a **tablet** form. This formulation also contains the active substance **metformin hydrochloride**. Similar to the METFORMIN coated tablet, the maximum daily dose is 2500 mg, administered orally, with a treatment duration of up to 48 weeks. The trial does not involve any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatment. Participant compliance is monitored throughout the study to ensure accurate assessment of the treatment's efficacy and safety.

Efficacy in the clinical trial titled "Optimizing metformin use in polycystic ovary syndrome - A randomized controlled trial" will be assessed using a range of primary and secondary endpoints. The primary endpoints include anthropometric measurements such as weight, **androgenicity** indicators like hirsutism and testosterone levels, metabolic parameters including HOMA-IR, gastrointestinal side-effects such as nausea, vomiting, and abdominal pain, and polycystic ovary morphology assessed by AMH levels. Secondary endpoints will further evaluate androgenicity through FAI, SHBG, DHEAS, androstenedione, free testosterone, acne, and alopecia. Menstrual cyclicity will be assessed via a questionnaire regarding the duration of the two previous cycles. Quality of life and weight stigma will be evaluated, focusing on anxiety and weight stigma. Additional metabolic parameters include fasting glucose, fasting insulin, HbA1C, lipids, CRP, ALAT, GGT, OGTT, FLI, Matsuda Index, and TyG index. Polycystic ovary morphology will be examined using ultrasound to determine follicle number per ovary and ovarian volume. Anthropometric measures will also include BMI, waist-hip ratio, WC, BAI, body composition, blood pressure, and pulse.