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The aim of the present study was to investigate the effect of the E23K variant of the potassium inwardly rectifying channel, subfamily J, member 11 ( KCNJ11) gene on gliclazide modified release ( MR) treatment in newly diagnosed patients with type 2 diabetes mellitus (T2 DM). A total of 108 diabetic patients with no history of antidiabetic medication was treated with gliclazide MR for 16 weeks and underwent follow up at Weeks 2, 4, 8, 12 and 16. All patients were genotyped for KCNJ11 E23K (rs5219). At baseline, patients with the KK genotype had higher blood glucose and lower serum insulin levels after oral glucose administration than patients with the EE and EK genotypes ( P < 0.05 for all). During treatment, individuals with the KK genotype had lower fasting glucose levels and were more likely to attain the target fasting glucose level ( Plog rank = 0.028) than E allele carriers. Patients with the KK genotype had larger augmentations in changes (Δ) in acute insulin response ( P = 0.049) and Δ body mass index ( P = 0.003). Moreover, patients with the EK genotype had a lower variance in changes in fasting insulin levels ( P = 0.049) and homeostasis model assessment of β-cell function (P = 0.021) than those with the KK genotype. The findings of the present study suggest that the KCNJ11 E23K variant is associated with a greater effect of sulphonylurea treatment in newly diagnosed Chinese patients with T2 DM. [ABSTRACT FROM AUTHOR]