Metformin Treatment in Patients With Type 2 Diabetes and Chronic Kidney Disease Stages 3A, 3B, or 4
Metformin Treatment in Patients With Type 2 Diabetes and Chronic Kidney Disease Stages 3A, 3B, or 4
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DOI：
10.2337/dc17-2231
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发表时间：
2018-03-01
期刊：
影响因子：
16.2
通讯作者：
De Broe, Marc E.
中科院分区：
文献类型：
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作者：
Lalau, Jean-Daniel;Kajbaf, Farshad;De Broe, Marc E.
本研究旨在确定二甲双胍治疗中重度慢性肾脏疾病的安全、有效的剂量方案（CKD;分别为3A/3B和4期），在没有前瞻性安全性和有效性研究的情况下，解除了对中重度CKD糖尿病患者使用二甲双胍的限制后。1）在CKD 1 - 5期中的剂量探索研究，其中在每次剂量增加后的1周期间评估二甲双胍的血液浓度; 2）一项为期4个月的二甲双胍治疗研究，用于验证最佳二甲双胍剂量与CKD分期的关系（3A、3B和4），每月监测血液二甲双胍、乳酸盐和HbA（1c）浓度;和3）在3A、3B和4期稳态CKD中施用单剂量二甲双胍后的药代动力学参数的评估。首先，在剂量探索研究中，CKD 3A期的适当每日给药方案为1，500 mg（早晨0.5 g [qam]+晚上1 g [qpm]），CKD 3B期为1，000 mg（0.5 g qam +0.5 g qpm），CKD 4期为500 mg（qam）。其次，在这些方案治疗4个月后，患者显示稳定的二甲双胍浓度，从未超过普遍接受的安全上限5.0 mg/L。无高乳酸血症（> 5 mmol/L）（心肌梗死患者除外），HbA（1c）水平无变化。第三，有CKD阶段groups.CONCLUSIONSProvided剂量调整肾功能之间的药代动力学参数没有显着差异，二甲双胍治疗似乎是安全的，仍然是有效的中重度CKD。
OBJECTIVEThis 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 METHODSThree 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 HbA(1c) 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.RESULTSFirst, 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 HbA(1c) levels did not change. Third, there were no significant differences in pharmacokinetic parameters among the CKD stage groups.CONCLUSIONSProvided that the dose is adjusted for renal function, metformin treatment appears to be safe and still pharmacologically efficacious in moderate-to-severe CKD.