Liraglutide as a Novel Strategy for Improving Metabolic and Hormonal Profiles in Obese Women with Polycystic Ovary Syndrome

Abstract

Purpose: This study aimed to investigate the effect of liraglutide and metformin as monotherapies on the hormonal, metabolic and clinical parameters of Poly Cystic Ovary Syndrome (PCOS). Participants were assigned to receive either Liraglutide (gradually titrated up to 3.0 mg/day as tolerated), Metformin (1000 mg/day), or standard lifestyle modification as a control group for 6 months.

Methods: A randomized, parallel, clinical trial was conducted on 150 patients (50 per group) who completed the study, out of 183 initially randomized patients diagnosed with PCOS.

Results: Out of 183 randomized patients, 150 completed the 24-week protocol (n = 50 per group). Most baseline characteristics were comparable across groups. Following 24 weeks of treatment, baseline-adjusted linear regression demonstrated that liraglutide induced significantly greater weight reduction compared to control (adjusted mean difference: -10.13 kg, FDR-adjusted p < 0.001). Furthermore, liraglutide yielded substantial improvements in insulin resistance, as evidenced by a significantly lower HOMA-IR compared to control (adjusted mean difference: -0.58, FDR-adjusted p < 0.001). Menstrual cycle regularity markedly improved in the liraglutide group (76.0%) compared to metformin (50.0%) and control (32.0%) (p < 0.001). Clinical pregnancy rates were 29.0% Control, 65.7% Liraglutide, 52.9% Metformin; overall between-group difference remained significant after FDR correction (χ²=9.026, FDR-adjusted p=0.044). Nausea, heartburn, and constipation were more frequent with liraglutide than metformin.

Conclusion: Liraglutide is significantly more effective than metformin in improving body weight, glycemic control, and menstrual frequency in women with PCOS and metabolic dysfunction. These findings support liraglutide as a primary therapeutic approach, particularly in obesity-associated PCOS. It was registered at ClinicalTrials.gov under the identifier NCT05965908, registered on July 20, 2023.