title: The role of genetic factors and kidney and liver function in glycemic control in type 2 diabetes patients on long-term metformin and sulphonylurea cotreatment.
abstract: This study investigated the influence of genetic polymorphisms of metformin transporters on long-term glycemic control and lipid status in type 2 diabetes patients in the everyday clinical setting. In total 135 patients treated with combination of metformin and sulphonylurea for at least 6 months were genotyped for SLC22A1 rs628031 and SLC47A1 rs2289669 polymorphisms. Relatively good blood glucose control with median HbA1c 6.9 (6.4-7.6) % was achieved on prescribed metformin dosage of 2550 (2000-2550) mg per day. Only 28 (20.7%) patients experienced mild hypoglycemia events, while no severe hypoglycemia events were observed. Most patients had normal or mildly impaired renal function. Parameters indicating renal function were not correlated with fasting glucose, HbA1c, or lipid parameters. Rs628031 and rs2289669 had minor allele frequencies of 0.385 and 0.355, respectively, and were not associated with HbA1c levels. Rs628031 was marginally associated with risk for hypoglycemia events (P = 0.046; OR = 0.51; 95% CI 0.26-0.99), while significant correlation was observed between rs2289669 and total cholesterol levels (P = 0.018). In conclusion, in patients on long-term metformin and sulphonylurea combination treatment, metformin transporters polymorphisms do not play a major role in glycemic control; however, they may influence lipid status.
authors.affiliation: General Hospital Trbovlje, Rudarska cesta 9, 1420 Trbovlje, Slovenia.
authors.forename: Jasna
authors.initials: J
authors.lastname: Klen
authors.affiliation: Pharmacogenetics Laboratory, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia.
authors.forename: Katja
authors.identifier: 0000-0001-5673-4458
authors.initials: K
authors.lastname: Goričar
authors.affiliation: Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Center Ljubljana, Zaloška cesta 2, 1000 Ljubljana, Slovenia.
authors.forename: Andrej
authors.initials: A
authors.lastname: Janež
authors.affiliation: Pharmacogenetics Laboratory, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia.
authors.forename: Vita
authors.initials: V
authors.lastname: Dolžan
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D004338:Drug Combinations; D005260:Female; D005838:Genotype; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male; D008687:Metformin / Q000008:administration & dosage*; D008875:Middle Aged; D027701:Organic Cation Transport Proteins / Q000235:genetics; D027702:Organic Cation Transporter 1 / Q000235:genetics; D014508:Urea / Q000008:administration & dosage* / Q000031:analogs & derivatives
chemical_list: D001786:Blood Glucose; D004338:Drug Combinations; D006442:Glycated Hemoglobin; D008687:Metformin; D027701:Organic Cation Transport Proteins; D027702:Organic Cation Transporter 1; D014508:Urea; C521869:SLC47A1 protein, human