SUN-114 Comparative Analysis of Glucagon-Like Peptide-1 Receptor Agonists, Metformin, and Inositol in Managing Polycystic Ovary Syndrome: A Network Meta-Analysis

Abstract Disclosure: A. Omarion: None. Y. Ayasa: None. Z. Omarion: None. B. Jayouse: None. H. Ayesh: None. Background:Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine disorder linked to metabolic disturbances, including insulin resistance and obesity. While metformin is a widely accepted therapy for addressing metabolic symptoms in PCOS, recent advances highlight the potential of glucagon-like peptide-1 (GLP-1) receptor agonists and inositol to improve insulin sensitivity, weight management, and hormonal balance. Despite the promising efficacy of these treatments, comprehensive comparative data remain limited. This study systematically evaluates the efficacy and safety of GLP-1 receptor agonists, metformin, and inositol in managing PCOS-related metabolic outcomes, with a focus on the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and Body Mass Index (BMI).Methods:A systematic review of the literature identified 140 studies, of which six randomized controlled trials (RCTs) were included in this analysis. A network meta-analysis was conducted to evaluate changes in HOMA-IR and BMI among patients treated with GLP-1 receptor agonists, metformin, and inositol, both as monotherapies and in combination.Results:GLP-1 receptor agonists demonstrated significant reductions in BMI compared to placebo (mean difference [MD] -2.00, 95% confidence interval [CI] [-4.74; 0.74], p = 0.15) and metformin (MD -1.70, 95% CI [-3.67; 0.27], p = 0.09). Inositol showed a modest impact on BMI (MD 1.23, 95% CI [-3.08; 5.54], p = 0.58) and was comparable to metformin in improving HOMA-IR (MD 6.63, 95% CI [0.83; 12.44], p = 0.03). The combination of GLP-1 receptor agonists and metformin yielded no additional significant benefit in either outcome compared to monotherapy. Heterogeneity was observed in the included studies (I² > 80%).Conclusion:GLP-1 receptor agonists showed promising efficacy in reducing BMI and improving insulin resistance in women with PCOS, with performance comparable or superior to metformin and inositol. The combination of GLP-1 agonists with metformin did not demonstrate additive benefits. These findings suggest that GLP-1 receptor agonists may represent a valuable therapeutic option for managing PCOS-related metabolic dysfunction. Further large-scale RCTs are warranted to validate these results. Presentation: Sunday, July 13, 2025