2型糖尿病最流行的治疗药物是二甲双胍。根据耶鲁大学研究人员在JAMA杂志上发表的回顾性研究发现，二甲双胍对伴有轻度至中度肾脏疾病的糖尿病患者也可能是安全的。

20年来，在美国二甲双胍已用于降低2型糖尿病患者的血糖。大多数专家认为是治疗2型糖尿病血糖升高最好的药物。尽管其有强大的安全性，但FDA已经长期推荐二甲双胍不被推荐治疗伴有轻度至中度肾脏疾病的糖尿病患者，原因是由于乳酸性酸中毒。但是，这些几十年前的FDA老的用药指引最近受到质疑。

Silvio E. Inzucchi,MD及其同事对已经发表的研究进行了系统回顾，评估二甲双胍在伴有轻度至中度肾脏疾病的糖尿病患者中引发乳酸性酸中毒的风险。他们发现，这些患者酸中毒的风险是非常低， 实际上相当于那些没有服用二甲双胍的糖尿病患者发生酸中毒的风险。

我们发现的是，没有现有证据表明二甲双胍是有风险的，Inzucchi说：只要糖尿病患者肾功能是稳定的，二甲双胍可安全地使用，肾功能不会受到严重损害。对于需要二甲双胍治疗糖尿病的老年患者，医生往往避免或停止二甲双胍处方治疗药物。

随着年龄的增长，患者的肾功能开始下降，大多数医生做的第一件事就是停止二甲双胍，Inzucchi说：下一个发生的是糖尿病得不到控制。虽然有其他药物可替代二甲双胍，但它们通常是不通用的产品，所以较为昂贵，并且还有更多的副作用。

同时研究人员警告说，研究结果并不适用于严重肾脏疾病的糖尿病患者。在有一定肾功能水平患者中，二甲双胍的剂量可能会需要降低，并且患者将需要更密切地监测以确保肾功能保持稳定。

doi:10.1001/jama.2014.15298

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Metformin in Patients With Type 2 Diabetes and Kidney Disease.

Silvio E. Inzucchi, Kasia J. Lipska, Helen Mayo, Clifford J. Bailey, Darren K. McGuire.

Importance Metformin is widely viewed as the best initial pharmacological option to lower glucose concentrations in patients with type 2 diabetes mellitus. However, the drug is contraindicated in many individuals with impaired kidney function because of concerns of lactic acidosis.

Objective To assess the risk of lactic acidosis associated with metformin use in individuals with impaired kidney function.

Evidence Acquisition In July 2014, we searched the MEDLINE and Cochrane databases for English-language articles pertaining to metformin, kidney disease, and lactic acidosis in humans between 1950 and June 2014. We excluded reviews, letters, editorials, case reports, small case series, and manusc**ts that did not directly pertain to the topic area or that met other exclusion criteria. Of an original 818 articles, 65 were included in this review, including pharmacokinetic/metabolic studies, large case series, retrospective studies, meta-**yses, and a clinical trial.

Results Although metformin is renally cleared, drug levels generally remain within the therapeutic range and lactate concentrations are not substantially increased when used in patients with mild to moderate chronic kidney disease （estimated glomerular filtration rates, 30-60 mL/min per 1.73 m2）。 The overall incidence of lactic acidosis in metformin users varies across studies from approximately 3 per 100?000 person-years to 10 per 100?000 person-years and is generally indistinguishable from the background rate in the overall population with diabetes. Data suggesting an increased risk of lactic acidosis in metformin-treated patients with chronic kidney disease are limited, and no randomized controlled trials have been conducted to test the safety of metformin in patients with significantly impaired kidney function. Population-based studies demonstrate that metformin may be prescribed counter to prevailing guidelines suggesting a renal risk in up to 1 in 4 patients with type 2 diabetes mellitus—use which, in most reports, has not been associated with increased rates of lactic acidosis. Observational studies suggest a potential benefit from metformin on macrovascular outcomes, even in patients with prevalent renal contraindications for its use.

Conclusions and Relevance Available evidence supports cautious expansion of metformin use in patients with mild to moderate chronic kidney disease, as defined by estimated glomerular filtration rate, with appropriate dosage reductions and careful follow-up of kidney function.