Comparison of metformin with inositol versus metformin alone in women with polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials

Purpose Metformin was the first medication targeting insulin resistance in PCOS, and it has been extensively studied as a metabolic treatment option. In recent years, inositols have emerged as potential treatment options for PCOS, but confidence in the available evidence supporting their use is limited. Methods We comprehensively searched PubMed, Embase, and Cochrane databases for RCTs comparing the use of combined metformin and inositol versus metformin alone in women with PCOS. A random-effects model was used to calculate the risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs). A p-value of <0.05 was deemed as statistically significant. Results Six RCTs and 388 patients were included in the analysis, with follow-up ranging from 3 to 6 months. Combination therapy was significantly associated with improved menstrual cycle regularity (RR 1.56; 95% CI 1.01 to 2.41; p = 0.04), and lower values of modified Ferriman-Gallwey score (MD -0.97; 95% CI -1.53 to -0.40; p < 0.01) and LH/FSH ratios (MD -0.13; 95% CI -0.24 to -0.03; p = 0.01). Differences in acne (p = 0.58), body mass index (p = 0.13), fasting blood glucose (p = 0.07) and HOMA-IR (p = 0.25) were not statistically significant. Conclusion In this meta-analysis of RCTs, combination therapy was associated with cycle regularization and reduction in hirsutism and LH/FSH ratio compared to metformin monotherapy. Further studies are needed to clarify the true benefits of the use of inositol in PCOS treatment.