Polycystic ovary syndrome (PCOS) is a complex endocrine-metabolic disorder, and while metformin is widely used in its management, its efficacy remains variable. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as potential alternatives due to their metabolic benefits. In this systematic review, we have evaluated the effectiveness of GLP-1 RAs on body mass index (BMI), homeostatic model assessment of insulin resistance (HOMA-IR), and total testosterone (TT) in women with PCOS. Randomised controlled trials (RCTs) comparing the effect of GLP-1 RAs with metformin, standard, or placebo on BMI, HOMA-IR, and TT in women with PCOS were selected following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 guidelines. A comprehensive literature search was conducted in various databases, including PubMed, Scopus, Embase, MEDLINE, Web of Science, Cochrane, and CINAHL through May 20, 2025. Eighteen RCTs comparing GLP-1 RAs with placebo, metformin, or standard therapy were included. Quality assessment was done using Cochrane's 'Risk of Bias tool (RoB2)'. Review Manager (RevMan) version 5.4.1 (The Cochrane Collaboration, London, United Kingdom) was used to perform random-effects meta-analysis. Continuous outcomes were pooled as mean differences (MD) when measured on the same scale and as standardised mean differences (SMD) when the scales differed, each with a 95% confidence interval (CI). Inter-study heterogeneity among the trials was assessed using the chi-squared test for heterogeneity, with I² to quantify the level of heterogeneity. The certainty of evidence was determined using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. GLP-1 RAs significantly reduced BMI compared with control interventions (MD: -1.09 kg/m²; 95% CI: -1.80 to -0.38; p = 0.003), with liraglutide showing superiority over both metformin and placebo in subgroup analyses. Insulin resistance improved significantly (SMD: -0.38; 95% CI: -0.61 to -0.16; p = 0.001), particularly with exenatide. However, no significant overall effect on TT levels was observed (SMD: -0.10; 95% CI: -0.38 to 0.18; p = 0.49). Risk of bias was generally low, with minor concerns in select domains. Funnel plots suggested minimal publication bias. The certainty of evidence was moderate for BMI and HOMA-IR and very low for TT. GLP-1 receptor agonists are effective in improving metabolic outcomes in PCOS, particularly in reducing BMI and insulin resistance. However, their effect on androgen levels remains inconclusive. These agents may represent a promising therapeutic option, especially in overweight or obese women with PCOS, though further large-scale studies are needed to confirm long-term benefits.
