Insulin Resistance, Metabolic Syndrome, Polycystic Ovary Syndrome
Conditions
Keywords
PCOS, Metformin, Myo-inositol, Dietary Restriction, Insulin Resistance, Weight Loss, Combination Therapy
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.
Detailed description
This is a 12-week, prospective, randomized, parallel-group controlled clinical trial conducted at an academic tertiary-care center in Islamabad, Pakistan (July-October 2025). The trial compares the independent and combined effects of metformin, inositol, and calorie restriction on metabolic, anthropometric, hormonal, and reproductive outcomes in women with polycystic ovary syndrome (PCOS). Participants A total of 192 reproductive-aged women (18-35 years) with PCOS diagnosed by Rotterdam criteria (≥2 of: oligo/anovulation, clinical/biochemical hyperandrogenism, polycystic ovarian morphology on ultrasound) will be enrolled. Key exclusions include thyroid dysfunction, hyperprolactinemia, congenital adrenal hyperplasia, Cushing syndrome, hepatic/renal impairment, pregnancy or lactation, and use of hormonal therapy or insulin-sensitizing agents within the preceding 3 months. Randomization and masking Participants will be randomized in a 1:1:1:1 allocation (n=48 per group) using a computer-generated sequence, with allocation concealment using sequentially numbered, opaque, sealed envelopes. Due to the nature of interventions, participant blinding is not feasible; however, laboratory personnel and data analysts will remain blinded to group assignment. Interventions (12 weeks) Group A (Metformin): metformin 1500-2000 mg/day orally, titrated according to gastrointestinal tolerance. Group B (Inositol): myo-inositol 2 g plus D-chiro-inositol 50 mg, taken twice daily. Group C (Calorie-restricted diet): individualized dietary counseling targeting 1200-1500 kcal/day with emphasis on low-glycemic carbohydrates, lean protein, and high-fiber foods. Group D (Combination): metformin + inositol + calorie-restricted diet as above. Participants will be followed every two weeks for adherence assessment and adverse event monitoring. Medication adherence will be assessed by pill counts. Dietary adherence will be assessed using weekly dietary logs and summarized as percent compliance with prescribed caloric intake. Outcomes Primary outcomes assessed at baseline and 12 weeks include: Anthropometric measures: weight, BMI, waist circumference; Metabolic measures: fasting glucose, fasting insulin, and insulin resistance (HOMA-IR; calculated as \[fasting insulin × fasting glucose\]/405); Menstrual regularity, defined as cycle length 21-35 days during the final four weeks of the intervention. Secondary outcomes include serum total testosterone, LH, FSH, LH/FSH ratio, Ferriman-Gallwey score, adherence, and adverse events. Fasting blood samples will be collected and hormonal assays performed using standardized chemiluminescence immunoassay platforms. Statistical approach Normality will be assessed using Shapiro-Wilk tests. Continuous variables will be summarized as mean ± SD. Within-group changes will be analyzed using paired t-tests. Between-group comparisons will use one-way ANOVA with Tukey HSD post-hoc testing. Effect sizes will be reported as partial eta-squared (η²). Categorical outcomes (e.g., menstrual regularity) will be compared using chi-square tests. Statistical significance will be defined as p \< 0.05. Analyses will follow CONSORT reporting principle
Interventions
DRUGMetformin Hydrochloride
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.
DIETARY_SUPPLEMENTMyo-Inositol
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.
BEHAVIORALDietary Restriction
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.
COMBINATION_PRODUCTMetformin + Myo-inositol + Dietary Restriction
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.
Sponsors
Islamabad Medical and Dental College
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Due to the nature of the interventions (drug and lifestyle), the study was conducted in an open-label manner.
Intervention model description
Four-arm, randomized, parallel-group comparative trial.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
Females aged 18 to 40 years. Diagnosed with polycystic ovary syndrome (PCOS) based on Rotterdam criteria (at least two of the following: oligo/anovulation, hyperandrogenism, polycystic ovaries on ultrasound). 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. \-
Exclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in insulin resistance (HOMA-IR) | Baseline to 12 weeks | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in body weight and body mass index (BMI) | Baseline to 12 weeks | Mean change in body weight (kg) and body mass index (kg/m²) from baseline to 12 weeks. |
| Change in menstrual cycle regularity | Baseline to 12 weeks | Proportion of participants achieving regular menstrual cycles or improvement in cycle regularity over the 12-week intervention period.Baseline to 12 weeks |
| Change in serum androgen levels | Baseline to 12 weeks | Mean change in serum total testosterone levels from baseline to 12 weeks |
Countries
Pakistan
Contacts
STUDY_DIRECTORShemaila Saleem
Shaheed Zulfiqar Ali Bhutto Medical University
Outcome results
None listed