2型糖尿病最流行的治療藥物是二甲雙胍。根據(jù)耶魯大學(xué)研究人員在JAMA雜志上發(fā)表的回顧性研究發(fā)現(xiàn)，二甲雙胍對伴有輕度至中度腎臟疾病的糖尿病患者也可能是安全的。

    20年來，在美國二甲雙胍已用于降低2型糖尿病患者的血糖。大多數(shù)專家認(rèn)為是治療2型糖尿病血糖升高最好的藥物。盡管其有強(qiáng)大的安全性，但FDA已經(jīng)長期推薦二甲雙胍不被推薦治療伴有輕度至中度腎臟疾病的糖尿病患者，原因是由于乳酸性酸中毒。但是，這些幾十年前的FDA老的用藥指引最近受到質(zhì)疑。

    Silvio E. Inzucchi,MD及其同事對已經(jīng)發(fā)表的研究進(jìn)行了系統(tǒng)回顧，評估二甲雙胍在伴有輕度至中度腎臟疾病的糖尿病患者中引發(fā)乳酸性酸中毒的風(fēng)險。他們發(fā)現(xiàn)，這些患者酸中毒的風(fēng)險是非常低， 實際上相當(dāng)于那些沒有服用二甲雙胍的糖尿病患者發(fā)生酸中毒的風(fēng)險。

    我們發(fā)現(xiàn)的是，沒有現(xiàn)有證據(jù)表明二甲雙胍是有風(fēng)險的，Inzucchi說：只要糖尿病患者腎功能是穩(wěn)定的，二甲雙胍可安全地使用，腎功能不會受到嚴(yán)重?fù)p害。對于需要二甲雙胍治療糖尿病的老年患者，醫(yī)生往往避免或停止二甲雙胍處方治療藥物。

    隨著年齡的增長，患者的腎功能開始下降，大多數(shù)醫(yī)生做的第一件事就是停止二甲雙胍，Inzucchi說：下一個發(fā)生的是糖尿病得不到控制。雖然有其他藥物可替代二甲雙胍，但它們通常是不通用的產(chǎn)品，所以較為昂貴，并且還有更多的副作用。

    同時研究人員警告說，研究結(jié)果并不適用于嚴(yán)重腎臟疾病的糖尿病患者。在有一定腎功能水平患者中，二甲雙胍的劑量可能會需要降低，并且患者將需要更密切地監(jiān)測以確保腎功能保持穩(wěn)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.