Free Fatty Acid and Amino Acid Predictors of Response to Metformin in Polycystic Ovary Syndrome

Metformin is one of the most widely used antidiabetic drugs and is also effectively used in treating women with polycystic ovary syndrome (PCOS). Our global objective is to separate women with PCOS into subtypes by their response to metformin. This pilot study aims to determine which free fatty acids and amino acids metabolites predict response to metformin as categorized by changes in insulin sensitivity and testosterone concentrations after three months of metformin therapy. We recruited 42 participants with PCOS aged between 18-50 years. Participants were randomly categorized into metformin (n= 29; 32.41 ± 7.4 years) and placebo groups (n=13; 32.15 ± 5.65 years). The Metformin group was challenged with three months of metformin titrated to at least 1500 mg daily. Body weights decreased significantly in the metformin treatment group from 98.55 ± 22.76 to 97.27 ± 23.14 (p-value=0.01) but did not change in the placebo group. Fasting plasma glucose decreased only in the metformin group from 89.25 ± 9.12 to 86.37 ± 9.53. Testosterone levels decreased in the metformin-treated group after 12 weeks from 29.0 (18.5 - 35.5) to 23.0 (15.5 - 32.5), but no significant change was observed in the placebo group from 28.0 (20.0 - 43.0) to 27.0 (21.5 -49.0). However, we did not observe a statistically significant change in insulin sensitivity values in PCOS and placebo groups. Linear regression analysis was performed to check the predictive power of those associated metabolites with delta values of testosterone and insulin sensitivity. Our results showed that changes in insulin sensitivity and testosterone levels after metformin treatment could be significantly predicted by using concentrations of metabolites (Fig.1). Disclosure A.Y. Chang: None. A.K. Asokan: None. D. Sakrikar: Employee; The Binding Site. A. Lalia: None. I.R. Lanza: None. M. Petterson: None. K. Nair: None. Funding National Institutes of Health (UL1TR000135)