Carriers of two reduced function alleles in CYP2C9 may experience an increased insulin response to glipizide and be predisposed to a higher risk of hypoglycaemia, although no effect of genotype was seen in glucose-based measurements.
The number of CYP2C9 deficient alleles was associated with nearly three-fold higher odds of hypoglycaemia (OR, 2.81; 95% CI, 1.30-6.09; P = .009) and better response to SU treatment (β, -0.218; SE, 0.074; P = .003) only in patients carrying the POR*1/*1 genotype.
Our results indicate that the CYP2C9 genotype may influence the risk for hypoglycemia events in elderly patients, but not in the overall population of type 2 diabetes patients.
In logistic regression analysis before and after adjustment for other factors known to affect this condition (age, body mass index, sulfonylurea mean daily dose, duration of T2DM, renal function and CYP2C9 genotype) KCNJ11 E23K polymorphism did not affect hypoglycemia risk.
CYP2C9 polymorphisms leading to decreased enzyme activity show a modest impact on the risk of mild hypoglycaemia attacks during oral antidiabetic treatment, with a significant association in patients treated with gliclazide.
In a model adjusted for age, BMI, mean daily dose of sulfonylurea, duration of T2DM and renal function, CYP2C9*1/*3 genotype increased the hypoglycemia risk in response to sulfonylurea (odds ratio: 1.687; p = 0.011).
The aim of this study was to test the hypothesis that individuals with genotypes predicting low CYP2C9 activity may be at a higher risk of severe drug-associated hypoglycaemia.