TY - JOUR
T1 - Association Between the CYP2C9 Genotype and Hypoglycemia Among Patients With Type 2 Diabetes Receiving Sulfonylurea Treatment
T2 - A Meta-analysis
AU - Yee, Jeong
AU - Heo, Yunhee
AU - Kim, Hamin
AU - Yoon, Ha Young
AU - Song, Gonjin
AU - Gwak, Hye Sun
N1 - Funding Information:
All the authors have made substantial contributions to the conception of the study. J.Y. Y.H. and H.S.G. contributed to designing the study. Y.H. H.K. and H.Y.Y. contributed to acquisition and analysis of data. J.Y. G.S. and H.S.G. contributed to interpretation of data. J.Y. and Y.H. contributed to drafting of the manuscript. H.S.G. contributed to critical revision of the manuscript. All authors approved the final manuscript.
Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/5
Y1 - 2021/5
N2 - 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.
AB - 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.
KW - CYP2C9
KW - hypoglycemia
KW - polymorphism
KW - sulfonylurea
KW - type 2 diabetes
UR - http://www.scopus.com/inward/record.url?scp=85104088036&partnerID=8YFLogxK
U2 - 10.1016/j.clinthera.2021.03.008
DO - 10.1016/j.clinthera.2021.03.008
M3 - Article
C2 - 33840516
AN - SCOPUS:85104088036
SN - 0149-2918
VL - 43
SP - 836-843.e4
JO - Clinical Therapeutics
JF - Clinical Therapeutics
IS - 5
ER -