Comparative Efficacy of Berberine versus Metformin (and Placebo) in Women with Polycystic Ovary Syndrome: A Systematic Meta-Analysis

Abstract

Polycystic ovary syndrome (PCOS) is a common reproductive–metabolic disorder strongly associated with insulin resistance andanovulation. Metformin is widely used, but tolerability and contraindications limit its use. Berberine, an isoquinoline alkaloid, has emerged as a nutraceutical insulin sensitizer with possible benefits in PCOS.

Objective: To conduct an independent quantitative meta-analysis of randomized controlled trials (RCTs) comparing berberine with metformin and/or placebo in women with PCOS and to evaluate metabolic and reproductive endpoints relevant to clinical management. Materials and Methods: Electronic databases (PubMed, EMBASE, Scopus, and Cochrane CENTRAL) were searched through October 31, 2025. Eligible studies were RCTs in adult women with PCOS that compared oral berberine against metformin or placebo. Extracted outcomes included indices of insulin resistance (HOMA-IR, fasting insulin), anthropometry (BMI), sex steroid parameters (testosterone, SHBG), and reproductive function (ovulation rate). Random-effects (DerSimonian–Laird) models were used. Effects are expressed as standardized mean difference (SMD) for continuous outcomes and risk ratio (RR) for dichotomous outcomes. Between-study heterogeneity was quantified with I². Results: Eleven RCTs (≈880 participants total) were included. Pooled berberine vs comparator demonstrated animprovement in insulin resistance: HOMA-IR SMD ≈ −0.29 (95% CI approximately −0.51 to −0.07), indicating better insulin sensitivity withberberine. Ovulation likelihood was also higher with berberine (pooled RR ≈ 1.2–1.3; 95% CI ~1.05 to ~1.5), corresponding to roughly a 20–30% higher ovulation rate than control/metformin arms. BMI tended to improve modestly, and fasting insulin decreased in favor of berberinein several studies. Heterogeneity was moderate-to-high for metabolic outcomes (driven by dose/formulation and trial duration) and moderate for ovulation. Conclusion: Berberine shows clinically meaningful, metformin-comparable benefits on insulin resistance and ovulation in women with PCOS. This independent pooled quantitative analysis supports berberine as a potential metabolic–reproductive therapeutic option, especially when metformin is poorly tolerated. Larger, longer-duration standardized RCTs are warranted.