Effects of GLP-1 Receptor Agonists vs Metformin in Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis

Polycystic ovarian syndrome (PCOS) is a common endocrine disorder associated with significant metabolic and reproductive dysfunction. Although metformin has long been a cornerstone of PCOS management, glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) have emerged as promising alternatives, particularly for improving metabolic outcomes. This systematic review and meta-analysis aimed to evaluate the effects of GLP-1 RAs compared with metformin on metabolic, hormonal, and reproductive parameters in women with PCOS. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, randomized controlled trials (RCTs) comparing GLP-1 RAs with metformin in women diagnosed with PCOS were systematically identified and analyzed. Four eligible RCTs comprising a total of 218 participants were included. Statistical analyses were conducted using a fixed-effects model. Compared with metformin, GLP-1 RAs were associated with significant reductions in serum testosterone (standardized mean difference (SMD) = -0.327, p = 0.036), dehydroepiandrosterone sulfate (DHEA-S) (SMD = -0.528, p = 0.048), androstenedione (SMD = -0.523, p = 0.002), and insulin resistance as assessed by the homeostasis model assessment of insulin resistance (HOMA-IR) (SMD = 1.217, p < 0.001). However, substantial heterogeneity across studies and potential publication bias were observed. Overall, GLP-1 RAs were associated with favorable improvements in key hormonal and metabolic markers compared with metformin in women with PCOS, including reductions in androgen levels and improvements in insulin resistance. Although the available evidence is limited by a small number of short-term trials, the findings are encouraging. Larger, well-designed randomized controlled studies with longer follow-up durations are needed to confirm the sustainability of these effects and to support their translation into routine clinical practice, with standardized reporting of adverse events and treatment discontinuation to better characterize safety and tolerability.