CYP2C93 variant is associated with antidiabetes efficacy of gliclazide in Chinese type 2 diabetes patients

J Diabetes Investig. 2016 Sep;7(5):764-8. doi: 10.1111/jdi.12486. Epub 2016 Mar 8.

Abstract

Aims/introduction: The objective of the present study was to investigate the effects of CYP2C9*3 polymorphisms on the therapeutic response to gliclazide in type 2 diabetes patients.

Materials and methods: A total of 746 incident type 2 diabetes patients were included in this study. After enrolment, patients went on 4-week gliclazide monotherapy. Fasting plasma glucose was measured before and after treatment. Hypoglycemia episodes and lifestyle information were collected by weekly follow up. Genotyping of rs1057910 was carried out using the single base primer extension method. The t-test, analysis of variance and chisquare-test were used to evaluate the effects of rs1057910 alleles on the therapeutic response to gliclazide.

Results: After the therapy, fasting plasma glucose decreased significantly from 11.2 ± 2.7 mmol/L to 8.0 ± 2.2 mmol/L (P < 0.001). Patients with AC/CC genotypes of rs1057910 had a greater reduction of fasting plasma glucose (3.6 vs 3.0 mmol/L, P < 0.001; 31.4 vs 24.5%, P < 0.001) and a higher rate of treatment success (54.7 vs 37.5%, P < 0.001; 51.4 vs 32.3%, P < 0.001; 71.6 vs 48.3%, P < 0.001 for criterion 1, 2 and 3, respectively).

Conclusions: The present study showed that the polymorphism at rs1057910 significantly affected the therapeutic response of gliclazide in type 2 diabetes mellitus patients. The risk allele is associated with a greater decrease of fasting blood glucose and a higher rate of treatment success with gliclazide monotherapy.

Keywords: CYP2C9*3; Gliclazide; Type 2 diabetes mellitus.

MeSH terms

  • Blood Glucose / metabolism
  • China
  • Cytochrome P-450 CYP2C9 / genetics*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Genotype
  • Gliclazide / therapeutic use*
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Prospective Studies
  • Treatment Outcome

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Gliclazide