The effects of metformin and sitagliptin for polycystic ovary syndrome treatment are enhanced by combining them.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age, characterized by insulin resistance, chronic inflammation, and hormonal imbalances. Metformin is widely used in the treatment of this syndrome; however, existing evidence suggests that its effectiveness alone in improving PCOS-related parameters is limited. In recent years, reports have indicated that sitagliptin may improve ovarian cycles and ovulation in women with PCOS. This study was designed to evaluate and compare the effects of metformin, sitagliptin, and their combination in an estradiol valerate (EV)- induced animal model of PCOS. Adult female Wistar rats were divided into five groups: control (healthy and untreated), PCOS induced by subcutaneous injection of EV at a dose of 4 mg/kg, PCOS treated with metformin (500 mg/kg for 21 days), PCOS treated with sitagliptin (50 mg/kg for 21 days), and PCOS treated with a combination of metformin and sitagliptin (500/50 mg/kg for 21 days). The findings indicated that the combination therapy, compared to monotherapies, significantly improved metabolic indices (reduced glucose, insulin, and homeostasis model assessment - insulin resistance, regulated reproductive hormones (increased follicle-stimulating hormone, decreased luteinizing hormone and luteinizing hormone/follicle-stimulating hormone ratio), and decreased the expression of inflammatory and angiogenesis markers interleukin-6 and vascular endothelial growth factor. Furthermore, ovarian tissue structure was improved and the number of healthy follicles increased. These results suggest that the combination of metformin and sitagliptin, due to its multi-targeted effects, may be a more effective therapeutic approach than monotherapy for managing PCOS and warrants further clinical investigation.