The Pharmacogenetics of Metformin in Women with Polycystic Ovary Syndrome: A Randomized Trial.

Abstract

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 OCT1 (rs12208357 and rs72552763), HNF1A (rs1169288 and rs2464196), MATE1 (rs2289669 and rs2252281), MATE2-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 (insulinAUC , glucoseAUC 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.

• Authors: Andreas J T Pedersen, Tore Bjerregaard Stage, Dorte Glintborg, Marianne Andersen, Mette Marie Hougaard Christensen
• Journal: Basic & clinical pharmacology & toxicology (Basic Clin Pharmacol Toxicol) Vol. 122 Issue 2 Pg. 239-244 (Feb 2018) ISSN: 1742-7843 [Electronic] England
• PMID: 28834135 (Publication Type: Journal Article, Randomized Controlled Trial)
• Copyright: © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Chemical References

• Biomarkers
• Blood Glucose
• Contraceptives, Oral, Hormonal
• HNF1A protein, human
• Hepatocyte Nuclear Factor 1-alpha
• Hypoglycemic Agents
• Insulin
• Organic Anion Transport Protein 1
• Organic Cation Transport Proteins
• SLC47A1 protein, human
• SLC47A2 protein, human
• Triglycerides
• ethinyl estradiol-desogestrel combination
• Ethinyl Estradiol
• Desogestrel
• Metformin
• ATM protein, human
• Ataxia Telangiectasia Mutated Proteins

Topics

• Adult
• Ataxia Telangiectasia Mutated Proteins (genetics)
• Biomarkers (blood)
• Blood Glucose (drug effects, metabolism)
• Contraceptives, Oral, Hormonal (therapeutic use)
• Desogestrel (therapeutic use)
• Drug Therapy, Combination
• Ethinyl Estradiol (therapeutic use)
• Female
• Hepatocyte Nuclear Factor 1-alpha (genetics)
• Humans
• Hypoglycemic Agents (adverse effects, therapeutic use)
• Insulin (blood)
• Insulin Resistance
• Metformin (adverse effects, therapeutic use)
• Organic Anion Transport Protein 1 (genetics)
• Organic Cation Transport Proteins (genetics)
• Pharmacogenetics
• Pharmacogenomic Variants
• Polycystic Ovary Syndrome (blood, diagnosis, drug therapy, genetics)
• Time Factors
• Treatment Outcome
• Triglycerides (blood)
• Weight Loss (drug effects)
• Young Adult