Cyp2c9 Genotype and Clinical Effects of Gliclazide

IntroductionGliclazide is an oral antidiabetic agent. It belongs to sulfonurea derivatives and may be used as a second choice agent. It is known to be metabolized by cytochromes P450 (CYP) 2C9 and 2C19. Clinical data showing influence of genetic polymorphisms on patient’s individual outcomes are scarce. We evaluated effects of CYP2C9*2 and CYP2C9*3 polymorphisms on clinical response to gliclazide in Russian diabetic patients.Material and MethodsSeventy-four patients who were diagnosed with type 2 diabetes mellitus, did not have obesity and did not have contraindications were prescribed gliclazide in the initial dose of 30 or 60 mg/day based on clinical judgement of endocrinologist. During clinical observation the dose could be adjusted, or the medication could be changed in case of insufficient clinical effect or intolerance. After initial treatment adjustments, patients were followed up to 6 month. Glycated haemoglobin (HbA1c) and 24-hour monitoring of glucose levels were registered. Blood samples for genotyping were collected, and analysed after collection of all clinical data.ResultsTwenty-eight patients (38%) were carrying mutated CYP2C9 alleles *2 or *3. By the end of the observation all patients had target HbA1c levels. In the group of mutant alleles carriers 21 patients (86%) achieved target levels on initial dose of gliclazide, compared to 14 patients (37%) in the group of noncarriers (P < 0.001). Mean effective gliclazide dose in mutation carriers was 53 ± 13 mg; in non-carriers – 84 ± 26 mg (P < 0.01). Mild hypoglycemic episodes were observed in only 1 patient in the group of mutations non-carriers and in 4 patients carrying CYP2C9*2 or *3. The difference was not significant.ConclusionsPatients carrying CYP2C9*2 or *3 alleles achieved clinical effect on gliclazide alone more frequently, and required smaller doses. Frequency of hypoglycaemic episodes was not significantly different between the groups. IntroductionGliclazide is an oral antidiabetic agent. It belongs to sulfonurea derivatives and may be used as a second choice agent. It is known to be metabolized by cytochromes P450 (CYP) 2C9 and 2C19. Clinical data showing influence of genetic polymorphisms on patient’s individual outcomes are scarce. We evaluated effects of CYP2C9*2 and CYP2C9*3 polymorphisms on clinical response to gliclazide in Russian diabetic patients.