Influence of the SLCO1B3 Gene on Sulfonylurea Failure in Patients with Type 2 Diabetes in China

Abstract

Sulfonylureas are widely used class of drugs for the treatment of type 2 diabetes (T2DM). Recent research has demonstrated that SLCO1B3 functions as a determinant of the insulinotropic effect of glibenclamide at the tissue level. However, whether this gene can influence the efficacy of glibenclamide in type 2 diabetic patients is not currently well-understood. All of our study subjects were enrolled from the Xiaoke Pills Clinical Trial. The subjects were treated with glibenclamide, and followed for 48 weeks. The rs4149117 genotype (T334G) in the SLCO1B3 gene was identified by direct sequencing. Relationships between genotype and efficacy and safety outcomes were evaluated by logistic or linear regression models as appropriate. A total of 374 subjects were enrolled in this study. The average age was 54.4±8.9 years, the percentage of males was 52.9%, and 91% of participants finished the genotype analysis successfully. Logistic regression analysis demonstrated that there was no significant difference between genotype and treatment failure of glibenclamide under an additive genetic model after adjusting for age, sex, renal function and diabetes duration (OR=1.009, 95% CI 0.692-1.473, P=0.961). The linear regression model demonstrated that the rs4149117 mutation in SLCO1B3 was significantly associated with a reduction in FPG after 48 weeks of treatment, independent of age, sex, renal function and diabetes duration (P=0.017, beta=0.130). In safety outcome analysis, we observed that rs4149117 had no association with hypoglycaemia. The rs4149117 mutation in the SLCO1B3 gene is not associated with sulfonylurea efficacy.