This study aimed to evaluate the levels of Nesfatin-1 and Myonectin, to determine the efficacy of metformin therapy in treating patients with newly diagnosed Polycystic Ovary Syndrome-PCOS. Between the 1st September 2022 to 1st November 2022, a total of 90 blood samples were collected from females aged 18 to 35 years old. The samples were divided into three groups, G1 for women newly diagnosed with PCOS before treatment, G2 for the same patients after treatment with metformin, And C is a control group collected from healthy females with no previous history of the disease.  The study includes the determination concentration of sex hormones (Follicle stimulating hormones –FSH, Luteinizing hormone-LH and testosterone), in addition to Nesfatin-1, Myonectin, and liver enzymes (Aspartate aminotransferase-AST, alanine aminotransferase-ALT, and alkaline phosphatase-ALP) in sera of samples under investigation.
            The results obtained from the present study indicate that the level of FSH significantly increased in G1, and significantly decrease after treatment with metformin. While the LH level didn't show any significant difference between patient groups (G1 and G2) as compared with the control group. The level of testosterone significantly increased after treatment with metformin, with no significant difference between G1 and C. While the level of nesfatin-1, myonectin and ALP significantly elevated in sera of women with PCOS in G1, as compared with C, and then significantly decreased after treatment, With no significant change in the level of AST and ALT between patients and control groups. The results of the ROC curve analysis showed that the area under the curve –AUC values for nesfatin-1 and myonectin in G1  were 0.938 (sensitivity of 96.30%), and 0.935(Sensitivity of 85.19%) respectively. While the AUC for serum nesfatin-1 and myonectin in G2 was 0.910 (Specificity 96%) and 0.793(Specificity 82.76%) respectively. So we can conclude that an increase in the level of nesfatin-1 is most likely to be a diagnostic marker for polycystic ovary syndrome, while decreasing level after treatment with metformin and its return to a normal level may be an indicator of the therapeutic response to the disease.