Palakodeti, Sanjana

Abstract Disclosure: N. Lanka: None. S. Palakodeti: None. O. Oluwasolabomi: None. R. Nalam: None. G. Rangari: None. Introduction: PCOS is a complex condition with multifactorial etiology. GLP-1 RAs are used in insulin-resistant disorders like PCOS for their effects on weight and glycemic control. Recent studies suggest they may also improve follicular growth, endometrial health, ovulation, and fertility, independent of weight loss. This study evaluates the effects of GLP-1 RAs on anthropometric, metabolic, and reproductive parameters in PCOS. Methods: We followed PRISMA 2020 guidelines. We searched PubMed and Cochrane Library (2015-Feb 2025) using relevant keywords. We included RCTs and cohort studies with PCOS patients (per Rotterdam criteria) receiving GLP-1 RA monotherapy compared to placebo, metformin, or other interventions, reporting anthropometric, metabolic, or reproductive outcomes. Statistical analysis was performed using RevMan 5.4 with random-effects models, and heterogeneity was assessed using the I2 coefficient (p<0.05 considered significant). Results: We identified 73 studies, with 10 RCTs included (730 participants). Of these, 50.13% received GLP-1 RAs (49.5% liraglutide, 41% exenatide, 9.56% dulaglutide, 2.73% semaglutide), and 45.9% were controls (42.2% metformin, 20.3% placebo, others combination therapy). The meta-analysis findings are as follows: Anthropometric Outcomes: GLP-1 RAs caused significant reductions in BMI (9 studies, MD = -1.41, 95% CI: -1.73 to -1.10, p<0.00001, I2=100%) and waist circumference (8 studies, MD = -2.69, 95% CI: -4.06 to -1.32, p=0.0001, I2=100%). 1 study showed liraglutide reduced VAT (p=0.006). Metabolic Outcomes: GLP-1 RAs had a non-significant effect on HOMA-IR (7 studies, MD = -0.03, 95% CI: -0.82 to 0.76, p=0.94, I2=100%) and LDL (7 studies, MD = -0.45, 95% CI: -1.31 to 0.40, p=0.30, I2=100%). 3 studies showed improvement in OGTT, and 1 showed a significant reduction in HbA1C (p=0.015). Reproductive Health Outcomes: GLP-1 RAs caused a significant decrease in total testosterone (10 studies, MD = -0.78, 95% CI: -1.02 to -0.55, p<0.00001, I2=99%). LH decreased non-significantly (4 studies, MD = -1.96, 95% CI: -4.18 to 0.26, p=0.08, I2=99%), while FSH increased non-significantly (4 studies, MD = 0.29, 95% CI: -0.69 to 1.27, p=0.56, I2=99%). Two studies showed significant improvements in menstrual regularity with liraglutide and exenatide (p=0.0001 and <0.001, respectively). Conclusion: Our findings suggest GLP-1 RAs could become key therapies for managing this condition. However, heterogeneity among studies—due to differences in design, drug used, control, and dosing—requires further studies to explore optimal dosages, durations, combination therapies, and their impact on ovulation and fertility. Presentation: Monday, July 14, 2025