Risk of Lactic Acidosis or Elevated Lactate Concentrations in Metformin Users With Renal Impairment: A Population-Based Cohort Study
Risk of Lactic Acidosis or Elevated Lactate Concentrations in Metformin Users With Renal Impairment: A Population-Based Cohort Study
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DOI：
10.2337/dc13-3023
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发表时间：
2014-08-01
期刊：
影响因子：
16.2
通讯作者：
de Vries, Frank
中科院分区：
文献类型：
--
作者：
Eppenga, Willemijn L.;Lalmohamed, Arief;de Vries, Frank
目的：本研究的目的是确定与从未使用过二甲双胍的非胰岛素抗糖尿病药物(NIAD)的使用者相比，肾损害患者接受二甲双胍治疗是否与乳酸酸中毒或乳酸浓度升高的风险更高有关。从临床实践研究数据链接(CPRD)中确定了223,968名二甲双胍使用者和34,571名从未使用二甲双胍的糖尿病患者的研究设计和方法队列。主要结果被定义为CPRD代码乳酸酸中毒或血乳酸浓度记录<5 mmol/L。肾脏损害、二甲双胍剂量与乳酸酸中毒或乳酸浓度升高的风险之间的关系用时间依赖的COX模型来确定，并表示为危险比(HR)。结果目前服用二甲双胍的患者乳酸酸中毒或乳酸浓度升高的粗发病率为每10万人年7.4例(非患者组为每10万人年2.2例)。与未使用的患者相比，当前使用二甲双胍的患者发生乳酸酸中毒或乳酸浓度升高的风险与肾功能(调整后的HR为13.0[95%CI 2.36-72.0])显著相关。结论本研究与当前的建议一致，即应充分监测二甲双胍使用者的肾功能，如有必要，应调整二甲双胍的剂量，如果肾功能降至60毫升/分钟/1.73m2以下。
OBJECTIVEThe objective of this study was to determine whether treatment with metformin in patients with renal impairment is associated with a higher risk of lactic acidosis or elevated lactate concentrations compared with users of a noninsulin antidiabetic drug (NIAD) who had never used metformin.RESEARCH DESIGN AND METHODSA cohort of 223,968 metformin users and 34,571 diabetic patients who had never used metformin were identified from the Clinical Practice Research Datalink (CPRD). The primary outcome was defined as either a CPRD READ code lactic acidosis or a record of a plasma lactate concentration >5 mmol/L. The associations between renal impairment, dose of metformin, and the risk of lactic acidosis or elevated lactate concentrations were determined with time-dependent Cox models and expressed as hazard ratios (HRs).RESULTSThe crude incidence of lactic acidosis or elevated lactate concentrations in current metformin users was 7.4 per 100,000 person-years (vs. 2.2 per 100,000 person-years in nonusers). Compared with nonusers, risk of lactic acidosis or elevated lactate concentrations in current metformin users was significantly associated with a renal function 2 g) of metformin (adjusted HR 13.0 [95% CI 2.36-72.0]).CONCLUSIONSOur study is consistent with current recommendations that the renal function of metformin users should be adequately monitored and that the dose of metformin should be adjusted, if necessary, if renal function falls below 60 mL/min/1.73 m2.