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Metformin Treatment in Patients With Type 2 Diabetes and Chronic Kidney Disease Stages 3A, 3B, or 4
Diabetes Care ( IF 16.2 ) Pub Date : 2018-03-01 , DOI: 10.2337/dc17-2231
Jean-Daniel Lalau 1, 2 , Farshad Kajbaf 1, 2 , Youssef Bennis 3 , Anne-Sophie Hurtel-Lemaire 3 , Frans Belpaire 4 , Marc E. De Broe 5
Affiliation  

OBJECTIVE This study was conducted to define a safe, effective dose regimen for metformin in moderate and severe chronic kidney disease (CKD; stages 3A/3B and 4, respectively), after the lifting of restrictions on metformin use in patients with diabetes with moderate-to-severe CKD in the absence of prospective safety and efficacy studies.

RESEARCH DESIGN AND METHODS Three complementary studies were performed: 1) a dose-finding study in CKD stages 1–5, in which blood metformin concentrations were evaluated during a 1-week period after each dose increase; 2) a 4-month metformin treatment study for validating the optimal metformin dose as a function of the CKD stage (3A, 3B, and 4), with blood metformin, lactate, and HbA1c concentrations monitored monthly; and 3) an assessment of pharmacokinetic parameters after the administration of a single dose of metformin in steady-state CKD stages 3A, 3B, and 4.

RESULTS First, in the dose-finding study, the appropriate daily dosing schedules were 1,500 mg (0.5 g in the morning [qam] +1 g in the evening [qpm]) in CKD stage 3A, 1,000 mg (0.5 g qam + 0.5 g qpm) in CKD stage 3B, and 500 mg (qam) in CKD stage 4. Second, after 4 months on these regimens, patients displayed stable metformin concentrations that never exceeded the generally accepted safe upper limit of 5.0 mg/L. Hyperlactatemia (>5 mmol/L) was absent (except in a patient with myocardial infarction), and HbA1c levels did not change. Third, there were no significant differences in pharmacokinetic parameters among the CKD stage groups.

CONCLUSIONS Provided that the dose is adjusted for renal function, metformin treatment appears to be safe and still pharmacologically efficacious in moderate-to-severe CKD.



中文翻译:

2型糖尿病和慢性肾脏病3A,3B或4期患者的二甲双胍治疗

目的本研究旨在为中度和重度慢性肾脏疾病(二期糖尿病,分别为3A / 3B和4期)的二甲双胍确定安全有效的剂量方案,在没有前瞻性安全性和有效性研究的情况下严重CKD。

研究设计与方法进行了三项补充研究:1)在CKD 1-5期的剂量寻找研究,其中在每次剂量增加后的1周内评估血液中的二甲双胍浓度;2)为期4个月的二甲双胍治疗研究,用于根据CKD分期(3A,3B和4)验证最佳二甲双胍剂量,并每月监测血液中的二甲双胍,乳酸和HbA 1c浓度;和3)在稳态CKD阶段3A,3B和4中单次服用二甲双胍后评估药代动力学参数。

结果首先,在剂量寻找研究中,CKD 3A期的适当每日给药方案为1,500 mg(上午[qam] 0.5 g +晚上[qpm] +1 g),1,000 mg(0.5 g qam + 0.5)在CKD 3B期患者中的平均剂量为q qpm),在CKD 4期患者中为500 mg(qam)。第二,在这些方案治疗4个月后,患者显示出稳定的二甲双胍浓度,从未超过公认的安全上限5.0 mg / L。高脂血症(> 5 mmol / L)不存在(心肌梗死患者除外),HbA 1c水平没有变化。第三,CKD阶段组之间的药代动力学参数没有显着差异。

结论只要调整剂量以适应肾功能,二甲双胍治疗在中重度CKD中似乎是安全的,并且在药理学上仍然有效。

更新日期:2018-02-21
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