Myo-inositol versus Metformin in Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis of Anthropometric, Endocrine, Metabolic, and Reproductive Outcomes

Abstract Background: Polycystic ovary syndrome (PCOS) features metabolic and hyperandrogenic abnormalities. Myo-inositol and metformin are insulin-sensitizers with unclear comparative effectiveness. Objectives : To compare the anthropometric, endocrine, metabolic, and reproductive effects of myo-inositol and metformin in women with PCOS. Search Strategy : PubMed, Google Scholar, and Cochrane Library were searched from inception through August 26, 2025, in accordance with (PRISMA 2020) guidelines. Selection Criteria: Thirty-Two randomized controlled trials and observational studies comparing myo-inositol with metformin in women with PCOS were included. Data Collection and Analysis: Anthropometric, endocrine, metabolic, reproductive outcomes, and adverse effects assessed at three and six months of treatment. Forest plots were generated using Review Manager 5.4. Sensitivity and subgroup analyses were conducted with R 4.5.2. Meta-regression was performed to explore sources of heterogeneity. Certainty of evidence was assessed using the GRADE approach. Main Results: Anthropometric outcomes included BMI at six months (SMD 0.20, 95% CI −0.09 to 0.93; p = 0.11) was comparable. Metabolic outcome fasting insulin at six months (SMD −0.16, 95% CI −0.70 to 0.38; p = 0.57) was similar. Endocrine outcomes favored myo-inositol for testosterone at three months (SMD −0.32; p = 0.04) and the LH/FSH ratio at six months (SMD −1.26; p = 0.04). Myo-inositol was associated with fewer adverse effects (RR 0.23; p < 0.00001). Conclusion: Myo-inositol and metformin demonstrate largely comparable efficacy across key outcomes in PCOS, and superior tolerability favoring myo-inositol. Funding: There is no role of funding for this project. Key Words: Polycystic ovary syndrome; myo-inositol; metformin; insulin resistance; hyperandrogenism