Association Between the CYP2C9 Genotype and Hypoglycemia Among Patients With Type 2 Diabetes Receiving Sulfonylurea Treatment: A Meta-analysis

Purpose: Two common variants, CYP2C9*2 (Arg144Cys, rs1799853) and CYP2C9*3 (Ile359Leu, rs1057910), are known to reduce the catalytic function of the CYP2C9 enzyme. Because impaired catalytic function is likely to affect sulfonylurea metabolism, it is predictable that CYP2C9 loss-of-function alleles may increase the risk of sulfonylurea-induced hypoglycemia. This systematic review and meta-analysis aimed to assess the association between CYP2C9 genotype and hypoglycemia among patients with type 2 diabetes mellitus (T2DM) receiving sulfonylurea. Methods: We searched for studies on the association between CYP2C9 genotype and sulfonylurea-induced hypoglycemia among patients with T2DM, published through August 7, 2020, using PubMed, Web of Science, and EMBASE. Odds ratios (ORs) and 95% CIs were calculated. Findings: Five cohort studies and 2 case-control studies were included, and the total number of patients analyzed in this meta-analysis was 2769. The CYP2C9 variant alleles were associated with an increase in sulfonylurea-induced hypoglycemia compared with wild-type homozygote (OR = 1.24; 95% CI, 1.03–1.48). Compared with CYP2C9 wild-type homozygotes, CYP2C9*2 allele was associated with increased incidence of hypoglycemia (OR = 1.85; 95% CI, 1.18–2.89), whereas the CYP2C9*3 allele failed to show the statistical significance (OR = 1.67; 95% CI, 0.40–6.86; P = 0.48). Implications: On the basis of these results, CYP2C9 genotyping may be useful for predicting the risk of hypoglycemia during sulfonylurea treatment for T2DM.