Metformin's Impact on Follistatin and Oxyntomodulin in PCOS, and Comorbidities: Secondary Analysis of a Double-Blind RCT

Abstract Background: Abnormal secretion of incretins, particularly Glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and oxyntomodulin (OXM), have been observed in individuals with Type 2 diabetes mellitus and PCOS. OXM plays a crucial role in metabolism, including reducing food intake and improving insulin secretion to decrease liver fat accumulation. Metformin, an insulin-sensitizing hypoglycemic drug, is widely used in the PCOS treatment. However, the impact of metformin on circulating OXM levels remais unknown, and this study aims to investigate it. Design: This study presents a secondary analysis of a randomized double-blind clinical trial. Methods: Forty-five patients with PCOS were enrolled and randomly divided into two groups: one received metformin (n=21), and other received placebo (n=24). The study aimed to evaluate the levels of follistatin and oxyntomodulin before and after metformin tretament (1500mg/day). Blood levels of oxyntomodulin and follistatin were assessed by ELISA tests. Results: At the end of the study, 20 patients were evaluated, including 5 (25%) from the metformin group and 15 (75%) from the placebo group. There was no significant difference in the variation of follistatin and oxyntomodulin levels between the metformin and placebo groups. However, a significant difference in follistatin levels was observed among participants with hyperandrogenic and non-hyperandrogenic phenotypes. There was no significant difference in oxyntomodulin levels in different phenotypes. Conclusion: Treatment with metformin for 60 days did not have a impact on follistatin and oxyntomodulin levels. However, a significant difference was found in follistatin values between participants with hyperandrogenic and non-hyperandrogenic phenotypes. Trial registration: Brazilian Registration Platform for Clinical Studies - REBEC -ID RBR-47tvky – Date of fist registration: 04/07/2017/ Brazilian Health Ministry- ID 17127713.2.0000.5149.