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

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.