Abstract
Background
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.
Methods
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.
Results
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.
Conclusions
The rs4149117 mutation in the SLCO1B3 gene is not associated with sulfonylurea efficacy.
Key words
pharmacogenetics - sulfonylurea efficacy - hypoglycaemia - type 2 diabetes
