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The Pharmacogenetics of Metformin in Women with Polycystic Ovary Syndrome: A Randomized Trial
Author(s) -
Pedersen Andreas J. T.,
Stage Tore Bjerregaard,
Glintborg Dorte,
Andersen Marianne,
Christensen Mette Marie Hougaard
Publication year - 2018
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12874
Subject(s) - metformin , polycystic ovary , medicine , endocrinology , insulin resistance , population , desogestrel , insulin , ethinylestradiol , pharmacodynamics , metabolic syndrome , pharmacogenetics , obesity , pharmacokinetics , biology , genotype , gene , biochemistry , environmental health , family planning , research methodology
Polycystic ovary syndrome ( PCOS ) is the most common endocrine disorder affecting women of reproductive age. PCOS is associated with obesity, dyslipidaemia and insulin resistance, and metformin treatment may improve such metabolic features. The effect of genetic variants in key metformin transporters, their transcriptional regulators or in metformin target genes on metformin response in women with PCOS is unclear. Associations between pharmacodynamic responses to metformin (changes in weight, lipid profile, insulin sensitivity evaluated by oral glucose tolerance testing) and polymorphisms in OCT 1 (rs12208357 and rs72552763), HNF 1A (rs1169288 and rs2464196), MATE 1 (rs2289669 and rs2252281), MATE 2‐K (rs12943590) and ATM (rs11212617) were studied in 40 women with PCOS randomized to 12 months of treatment with metformin 1000 mg twice daily ± oral contraceptive pills (150 μg desogestrel + 30 μg ethinylestradiol). In the entire study population, treatment was associated with reduced weight (median weight change −2.4 kg, 25th–75th percentile −5.2 to 0.3 kg, p < 0.001) and increased triglycerides (0.2 mmol/L (0.0–0.6 mmol/L), p < 0.01) without significant changes in other lipid parameters or insulin sensitivity (insulin AUC , glucose AUC during OGTT ). None of the evaluated polymorphisms significantly affected any treatment outcome. In conclusion, the genetic variants investigated were not crucial for the clinical response to metformin in PCOS .