Metformin vs Inositol vs Diet vs Combination Therapy in PCOS
PCOS-COMBO (9)
Comparative Effectiveness of Metformin, Inositol, Dietary Restriction, and Combination Therapy in Polycystic Ovary Syndrome: A 12-Week Prospective Randomized Study
2 other identifiers
interventional
192
1 country
1
Brief Summary
Polycystic ovary syndrome (PCOS) is a common condition that can cause irregular periods, excess male-type hormones, weight gain, and insulin resistance. This study will compare four commonly used approaches for PCOS management: metformin, inositol, a calorie-restricted diet, and a combination of all three. A total of 192 women aged 18-35 years with PCOS (diagnosed using Rotterdam criteria) will be randomly assigned to one of four groups for 12 weeks: (A) metformin, (B) myo-inositol plus D-chiro-inositol, (C) calorie-restricted diet, or (D) combination therapy (metformin + inositol + diet). The study will assess changes in body weight, body mass index (BMI), waist circumference, fasting glucose, fasting insulin, insulin resistance (HOMA-IR), and menstrual regularity. Hormonal measures and safety outcomes will also be evaluated. The goal is to determine which approach provides the greatest overall metabolic and reproductive benefit in women with PCOS.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable
Started May 2025
Shorter than P25 for not_applicable
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
May 21, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 11, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
January 13, 2026
CompletedFirst Submitted
Initial submission to the registry
January 24, 2026
CompletedFirst Posted
Study publicly available on registry
February 2, 2026
CompletedFebruary 2, 2026
January 1, 2026
6 months
January 24, 2026
January 24, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Change in insulin resistance (HOMA-IR)
Mean change in insulin resistance as measured by the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), calculated from fasting plasma glucose and fasting serum insulin levels, comparing baseline values to 12-week follow-up among the four treatment groups (metformin, inositol, dietary restriction, and combination therapy).
Baseline to 12 weeks
Secondary Outcomes (3)
Change in body weight and body mass index (BMI)
Baseline to 12 weeks
Change in menstrual cycle regularity
Baseline to 12 weeks
Change in serum androgen levels
Baseline to 12 weeks
Study Arms (4)
Metformin Group
EXPERIMENTALParticipants will receive metformin hydrochloride tablets, 500 mg orally twice daily (total daily dose 1000 mg) after meals for 12 weeks. This arm evaluates the effect of metformin monotherapy on metabolic, hormonal, and clinical outcomes in women with polycystic ovary syndrome (PCOS).
Inositol Group
EXPERIMENTALParticipants will receive myo-inositol powder/sachets, 2 g orally twice daily (total daily dose 4 g) for 12 weeks. This arm evaluates the effect of inositol monotherapy on insulin resistance, hormonal profile, and clinical features of PCOS.
Dietary Restriction Group
EXPERIMENTALParticipants will follow a structured calorie-restricted diet (approximately 1200-1500 kcal/day, individualized according to baseline BMI), designed and supervised by the study team, for 12 weeks. No pharmacological treatment will be given. This arm evaluates the effect of dietary intervention alone on anthropometric, metabolic, and reproductive outcomes in PCOS.
Combination Therapy Group
EXPERIMENTALParticipants will receive metformin hydrochloride tablets 500 mg orally twice daily plus myo-inositol 2 g orally twice daily, along with the same structured calorie-restricted diet (1200-1500 kcal/day) for 12 weeks. This arm evaluates the combined effect of pharmacological and lifestyle intervention on metabolic, hormonal, and clinical outcomes in PCOS.
Interventions
This intervention combines pharmacological insulin sensitization and nutritional supplementation with lifestyle modification to evaluate the synergistic effect on metabolic, hormonal, and clinical outcomes in women with polycystic ovary syndrome.
A structured, supervised calorie-restricted dietary program is used as a lifestyle intervention to improve weight, metabolic parameters, and reproductive function in women with polycystic ovary syndrome.
Metformin is an insulin-sensitizing biguanide used to improve glucose metabolism and reduce insulin resistance in women with polycystic ovary syndrome. It is administered orally as part of the study protocol to evaluate its effects on metabolic, hormonal, and reproductive outcomes.
Myo-inositol is a nutritional supplement involved in insulin signaling pathways and ovarian function. It is used in this study to assess its effect on insulin sensitivity, hormonal profile, and clinical features of polycystic ovary syndrome.
Eligibility Criteria
You may qualify if:
- Body mass index (BMI) ≥ 18.5 kg/m². Willing to participate and provide written informed consent. Willing to comply with study procedures and follow-up visits.
You may not qualify if:
- Pregnancy or lactation. Known diabetes mellitus, thyroid disease, hyperprolactinemia, Cushing's syndrome, or other endocrine disorders.
- Use of metformin, inositol, hormonal therapy, or weight-loss drugs within the last 3 months.
- History of renal, hepatic, or cardiovascular disease. Known hypersensitivity to metformin or inositol. Participation in another clinical trial within the last 3 months. Any serious medical or psychiatric condition that, in the investigator's opinion, would interfere with study participation.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Pakistan Institute of Health Sciences / Islamabad Medical and Dental College (IMDC)
Islamabad, Islamabad, 44000, Pakistan
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Shemaila Saleem
Shaheed Zulfiqar Ali Bhutto Medical University
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- NONE
- Masking Details
- Due to the nature of the interventions (drug and lifestyle), the study was conducted in an open-label manner.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 24, 2026
First Posted
February 2, 2026
Study Start
May 21, 2025
Primary Completion
November 11, 2025
Study Completion
January 13, 2026
Last Updated
February 2, 2026
Record last verified: 2026-01
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
- Time Frame
- The data will be available beginning 6 months after publication of the primary results and will remain available for 5 years thereafter.
- Access Criteria
- Access to the data will be granted to researchers who provide a methodologically sound proposal, obtain approval from the principal investigator and the institutional ethics committee, and sign a data use agreement. Data will be used only for non-commercial, academic research purposes.
De-identified individual participant data (IPD) underlying the results reported in this study, including demographic, clinical, biochemical, and outcome variables, will be made available to qualified researchers upon reasonable request. Data will be shared in a de-identified format to protect participant confidentiality. Requests will be reviewed by the principal investigator and the institutional ethics committee.