Abstract Body (Do not enter title and authors here): Background Polycystic ovary syndrome (PCOS) is associated with early-onset cardiometabolic dysfunction, including insulin resistance and vascular impairment. Although glucagon-like peptide-1 receptor agonists (GLP-1RAs) are approved for metabolic disorders, their potential to improve both endocrine and endothelial parameters in PCOS remains under-investigated.

Objective To systematically assess the effects of GLP-1RAs on endothelial function and cardiometabolic risk markers in reproductive-age women with PCOS.

Methods Following PRISMA 2020 guidelines, we searched four databases (Embase, PubMed, Cochrane, Web of Science) for studies published from 2000 to May 31, 2025. Seven independent reviewers screened 631 records using Rayyan (450 after deduplication). Full-text assessment identified 18 eligible trials. Inclusion criteria: randomized or prospective cohort design, women aged 18–45 with diagnosed PCOS, and a GLP-1RA intervention of ≥12 weeks. Data were extracted on study design, drug type, duration, outcomes, and adverse events. Risk of bias was evaluated using RoB 2.0 for RCTs and the Newcastle–Ottawa Scale (NOS) for cohorts. A narrative synthesis was conducted due to heterogeneity in design and outcome reporting.

Results Eighteen trials (715 GLP-1RA-treated, 399 control participants; mean age 26 ± 4 y, BMI 33 ± 5 kg/m2) evaluated liraglutide (11), exenatide (5), or semaglutide (2). HOMA-IR decreased in 6/16 trials (typical absolute drop ≈ 1 unit); 9 were neutral, 1 increased. Systolic BP declined in 5/15 trials (≈ 2–6 mm Hg); 9 were neutral, 1 increased. LDL-C dropped in 7/13 trials (median ≈ 10 mg/dL); 5 were neutral, 1 increased. Endothelial function improved in both trials that assessed FMD (+2%, +3%). Adverse events were mild: transient nausea (15%) and injection-site discomfort (9%); no reports of pancreatitis or severe hypoglycemia.

Risk-of-bias summary: two low-risk, 13 some-concerns, and three high-risk studies, as assessed by RoB 2.0 and the Newcastle–Ottawa Scale (NOS).

Conclusions GLP-1RAs show consistent signals of benefit across insulin sensitivity, lipid metabolism, and vascular outcomes in women with PCOS, with favorable safety profiles.

Clinical Perspective Targeting early endothelial and metabolic dysfunction with GLP-1RAs may reduce long-term cardiovascular risk in PCOS; high-quality, longer-duration trials are needed.