Association of genetic variation in the organic cation transporters OCT1, OCT2 and multidrug and toxin extrusion 1 transporter protein genes with the gastrointestinal side effects and lower BMI in metformin-treated type 2 diabetes patients

Abstract

Two genetic variations in OCT1 that are in strong linkage disequilibrium may predispose toward an increased prevalence of the side effects of metformin in patients with T2D.

In Vivo Cytochrome P450 3A Isoenzyme Activity and Pharmacokinetics of Imatinib in Relation to Therapeutic Outcome in Patients With Chronic Myeloid Leukemia

“…The 1222A allele has previously been associated with efficacy and adverse events of metformin in diabetic patients. 37,38 Similar to our findings, a deletion in OCT-1 intron 7 (rs36056065), linked to the 1222A>G genotype, showed a significant influence on metformin adverse events. 38 This intronic variant is located only two nucleotides from the rs4646281 variant studied here.…”

“…37,38 Similar to our findings, a deletion in OCT-1 intron 7 (rs36056065), linked to the 1222A>G genotype, showed a significant influence on metformin adverse events. 38 This intronic variant is located only two nucleotides from the rs4646281 variant studied here. Decreased OCT-1 transcript levels of the 1222A allele in the liver were identified, but these differences were not statistically significant.…”

PharmGKB summary

“…A study by Tarasova and colleagues identified two coding variants, rs36056065 and rs628031, that were associated with the occurrence of side effects of metformin. Particularly, the authors observed that the presence of either variant may predispose a patient toward an increase in GI-related side effects following metformin therapy [26]. …”

Steady-State Pharmacokinetics of Metformin in Obese Patients With Type 2 Diabetes Mellitus: A Preliminary Study

“…This present study also revealed a quite large number of frequency of SNP rs628031 OCT1 in Indonesian T2DM patients, so further studies about the impact of this variant on gastrointestinal side effect and risk of hypoglycemia events as already reported in several studies [35,36] should be conducted for Indonesian population. As this research also found a variability of metformin peak PSSC, as well as a significantly higher level in metformin users, a pharmacogenetic and detailed pharmacokinetic study on monotherapy compared to combination therapy with sulfonylurea, are required to improve the therapeutic management of T2DM patients receiving metformin.…”