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BackgroundPolycystic Ovary Syndrome (PCOS) is a common endocrine disorder characterized by obesity, insulin resistance, and cardiometabolic risks. Lifestyle intervention is first-line therapy, but drug therapy is often necessary. Common treatments include metformin, myoinositol, and glucagon-like peptide-1 (GLP-1) receptor agonists. The comparative metabolic efficacy of these treatments remains unclear.MethodsWe conducted a systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs) according to PRISMA-NMA guidelines. Eligible studies recruited non-menopausal women with PCOS and evaluated GLP-1 receptor agonists, metformin, or myoinositol (± folic acid [FA]) alone or in combination versus placebo or active comparators. The primary outcome was body weight change, while secondary outcomes included body mass index (BMI), waist circumference, and Homeostasis Model Assessment for Insulin Resistance (HOMA-IR). Outcomes were synthesized using a frequentist random-effects NMA, and the CINeMA framework was used to assess certainty.ResultsSixteen RCTs were included. GLP-1 + metformin was the most effective intervention for weight reduction (MD −5.58 kg; 95% CI −8.57 to −2.59) and BMI decrease (MD −2.17; 95% CI −2.77 to −1.58). GLP-1 monotherapy also showed decreases in weight (MD −5.22 kg) and BMI (MD −2.00). Waist circumference was significantly reduced by GLP-1 alone (MD −4.70 cm). None ofthe interventions showed significant effects on HOMA-IR, and results were marked by heterogeneity. Sensitivity analyses confirmed robustness for weight and BMI outcomes.ConclusionsGLP-1 receptor agonists combined with metformin appear to be the most effective pharmacologic therapies for anthropometric improvement, specifically body weight and BMI reduction, in women with PCOS. These conclusions are limited to anthropometric and metabolic parameters, reproductive, endocrine, and patient-centered outcomes were not evaluated in this analysis and therefore no claims of overall superiority in PCOS management can be made. Further long-term and head-to-head RCTs including a broader range of outcomes are needed.Systematic Review Registrationhttps://osf.io/zyhws/, identifier 10.17605/OSF.IO/ZYHWS