Hormonal, metabolic and genetic predictors of metformin efficacy in patients with diabetes mellitus and cancer

Abstract

Aims: (1) To compare hormonal and metabolic profile of type 2 diabetes mellitus patients (T2DM) with or without neoplastic processes with the data from screening for SNPs affecting sensitivity to metformin. (2) To compare the abovementioned parameters including relevant genotype frequency in patients with positive and negative response to metformin. Materials and Methods; A total of 167 patients, all female, aged 43 to 88 years in menopause no shorter than 1 year, with or without history of T2DM were enrolled in this study. 156 patients underwent genetic screening for SNPs that were previously suggested as relevant to metformin efficacy. 55 patients received metformin 1000-1700 g daily with hormonal and metabolic monitoring and assessment of surrogate antineoplastic markers (such as endometrial thickness and mammographic density of mammary glands). Results: There was no unifying hormonal or metabolic phenotype for patients with given metformin-associated SNPs. However, we observed a certain trend for alterations in HOMA-IR and plasma estradiol levels. Dyslipidemia and elevated estradiol levels were positively associated with both types of positive response to metformin - 'metabolic' and 'antineoplastic' - though the latter was observed less frequently. Our data suggests that among 8 studied SNPs, the OCT1_R61C genotype (organic cation transporter-1) carriers require more close attention. Conclusion: Larger studies are required for further elucidation of the genetic background for metformin action in patients with various forms of cancer.