Li Cuilin, Yuan Xiangmin, Huang Li, Bai Zhuojun, Zheng Lian, Tan Yani, Liu Xin
Department of Pharmacy, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, China.
Health Management Center, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, China.
Pharmacol Res Perspect. 2025 Apr;13(2):e70090. doi: 10.1002/prp2.70090.
Metformin is a classical oral hypoglycemic drug, often recommended as the first-line therapy for type 2 diabetes mellitus (T2DM). Previous research has shown that the efficacy of metformin is associated with the genetic polymorphisms of patients. Considering the role of G6PC in gluconeogenesis and glycogenolysis, this study aims to investigate the association of G6PC rs161620 and rs2229611 with metformin efficacy in T2DM patients who take metformin only. According to the decrease of HbA1c, 116 T2DM patients receiving metformin monotherapy were divided into two groups: response group (the decrease of HbA1c by at least 1.5% after 3 months) and non-response group (the decrease of HbA1c < 1.5%). SNPscan technology was used to genotype. There were significant differences in rs161620 and rs2229611 presented in genotype frequency (p = 0.027 both) between the response group and the non-response group. According to the results of logistic analysis, the genetic polymorphisms of G6PC rs161620 or rs2229611 could influence the hypoglycemic effect of metformin in T2DM patients. We found that the decreasing values of PBG and HbA1c in G6PC rs161620 (C > A) or rs2229611 (T > C) mutants were significantly more than those in wild-type individuals, which means the more effective genotypes of metformin are CA/AA of rs161620 and TC/CC of rs2229611. This study suggested that the G6PC rs161620 and rs2229611 genetic polymorphisms were significantly associated with metformin efficacy in Chinese T2DM patients.
二甲双胍是一种经典的口服降糖药，常被推荐作为2型糖尿病（T2DM）的一线治疗药物。先前的研究表明，二甲双胍的疗效与患者的基因多态性有关。考虑到葡萄糖-6-磷酸酶（G6PC）在糖异生和糖原分解中的作用，本研究旨在探讨G6PC基因rs161620和rs2229611与仅服用二甲双胍的T2DM患者二甲双胍疗效之间的关联。根据糖化血红蛋白（HbA1c）的下降情况，将116例接受二甲双胍单药治疗的T2DM患者分为两组：反应组（3个月后HbA1c下降至少1.5%）和无反应组（HbA1c下降<1.5%）。采用SNPscan技术进行基因分型。反应组和无反应组之间，rs161620和rs2229611的基因型频率存在显著差异（两者p均=0.027）。根据逻辑分析结果，G6PC rs161620或rs2229611的基因多态性可影响二甲双胍在T2DM患者中的降糖效果。我们发现，G6PC rs161620（C>A）或rs2229611（T>C）突变体的餐后血糖（PBG）和HbA1c下降值显著高于野生型个体，这意味着二甲双胍更有效的基因型是rs161620的CA/AA和rs2229611的TC/CC。本研究表明，G6PC rs161620和rs2229611基因多态性与中国T2DM患者的二甲双胍疗效显著相关。
