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Mild hypoglycaemic attacks induced by sulphonylureas related to CYP2C9, CYP2C19 and CYP2C8 polymorphisms in routine clinical setting

  • Pharmacogenetics
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Aim

To evaluate the impact of polymorphisms in the cytochrome P450 (CYP) 2C9, 2C19 and 2C8 genes on the risk of mild hypoglycaemic attacks in patients treated with sulphonylureas.

Methods

One hundred and eight type 2 diabetic patients (50 men, 58 women), treated with oral antidiabetics, including at least one from the sulphonylurea group (glimepiride n = 50, gliclazide n = 46, or glipizide n = 12) for 3 months or longer, were included in the study. Symptoms of hypoglycaemia (sweating, tremor, anxiety and palpitations) during a 3 month period were recorded and confirmed by home glucose measurements. Gender, age, body mass index, creatinine clearance, HbA1c, oral antidiabetic dose and concomitant medication were assessed together with functional CYP2C9, CYP2C19 and CYP2C8 polymorphisms, analysed by real-time PCR methods.

Results

Fifteen patients (eight men, seven women) reported hypoglycaemia symptoms which were validated by their home glucose measurements (< 70 mg/dl). Heterozygosity and homozygosity for CYP2C9 variant alleles (*2 or *3) tended to be more frequent among patients who reported hypoglycaemic attacks (60 and 7%) than those who did not (39 and 3%). Similarly, the CYP2C8*1/*3 genotype tended to be more frequent in patients with (47%) than without (27%) hypoglycaemia, while no such trend was observed for CYP2C19 variants. However, only in the gliclazide group a significant association between CYP2C9 genotype and hypoglycaemic attacks was observed (P = 0.035). None of the other covariates showed any significant association with the risk of hypoglycaemic attacks.

Conclusions

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.

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Acknowledgements

The study has been financed by grants from the Swedish Research Council and the Scientific and Technological Research Council of Turkey.

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Authors and Affiliations

  1. Medical Faculty, Department of Pharmacology, Dicle University, Diyarbakir, Turkey

    Osman Gökalp

  2. Department of Medical Sciences, Clinical Pharmacology, Uppsala University, Uppsala, Sweden

    Arzu Gunes, Maria Gabriella Scordo & Marja-Liisa Dahl

  3. Medical Faculty, Department of Internal Medicine, Süleyman Demirel University, Isparta, Turkey

    Hakan Çam, Erkan Cure, Osman Aydın & Mehmet Numan Tamer

  4. Department of Clinical Pharmacology, Karolinska University Hospital, Stockholm, Sweden

    Marja-Liisa Dahl

  5. Swedish Medical Products Agency, Dag Hammarskjölds väg 42, 752 37, Uppsala, Sweden

    Arzu Gunes

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  1. Osman Gökalp
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Correspondence to Arzu Gunes.

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Gökalp, O., Gunes, A., Çam, H. et al. Mild hypoglycaemic attacks induced by sulphonylureas related to CYP2C9, CYP2C19 and CYP2C8 polymorphisms in routine clinical setting. Eur J Clin Pharmacol 67, 1223–1229 (2011). https://doi.org/10.1007/s00228-011-1078-4

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  • DOI: https://doi.org/10.1007/s00228-011-1078-4

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