Kalantar-Zadeh Kamyar, Kovesdy Csaba P
Harold Simmons Center for Chronic Disease Research and Epidemiology, Division of Nephrology and Hypertension, School of Medicine, University of California, Irvine, Irvine, CA Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA VA Long Beach Healthcare System, Long Beach, CA
The University of Tennessee Health Science Center, Memphis, TN Memphis VA Medical Center, Memphis, TN.
Diabetes Care. 2016 Jul;39(7):1281-6. doi: 10.2337/dc15-2327.
Metformin is and has been considered as first-line therapy for type 2 diabetes for over a quarter of a century. Like other biguanides, metformin can cause a lactic acidosis that is exceptionally rare but fatal. The likelihood of metformin-associated lactic acidosis is substantially higher in patients with kidney impairment and also among those with seemingly normal kidney function who are at risk of acute kidney injury (AKI). Hence, regulatory agencies in many industrialized nations have maintained strict renal restrictions surrounding metformin. However, there have been millions of people exposed to metformin for many years, many of them with serum creatinine values at or close to 1.5 mg/dL with estimated glomerular filtration rates (eGFRs) much below 60 mL/min/1.73 m(2) who have not developed lactic acidosis. Thus, there clearly remains controversy in this area, and there has been heightened pressure to remove the renal restrictions of metformin. To provide a discussion on the pros and cons of relaxing the renal restrictions for metformin use, we provide a Point-Counterpoint. In the point narrative below, Drs. Kalantar-Zadeh and Kovesdy provide their argument that although there is little evidence of the potential benefits of metformin in kidney disease, just considering the sheer numbers of metformin users and the high fatality rate of its associated lactic acidosis, the most appropriate practice is to avoid metformin use in people with eGFR <45 mL/min/1.73 m(2) or in those who are at high risk of AKI irrespective of underlying eGFR. In the following counterpoint narrative, Drs. Bakris and Molitch argue that the data from a very large analysis demonstrate clearly that serum creatinine should be supplanted with eGFR as the criteria for metformin use and that the incidence of lactic acidosis is only elevated in those with a reduced eGFR who become dehydrated for various reasons or in those exposed to some toxin resulting in AKI. Otherwise the data clearly support the use of metformin under normal circumstances down to eGFR >30 mL/min/1.73 m(2)-William T. CefaluEditor in Chief, Diabetes Care.
在超过四分之一世纪的时间里，二甲双胍一直被视为2型糖尿病的一线治疗药物。与其他双胍类药物一样，二甲双胍可引发乳酸酸中毒，这种情况极为罕见但会致命。在肾功能不全患者以及看似肾功能正常但有急性肾损伤（AKI）风险的患者中，二甲双胍相关乳酸酸中毒的可能性显著更高。因此，许多工业化国家的监管机构对二甲双胍维持了严格的肾脏相关限制。然而，已有数百万人多年来一直在使用二甲双胍，其中许多人的血清肌酐值达到或接近1.5mg/dL，估算肾小球滤过率（eGFR）远低于60mL/min/1.73m²，但并未发生乳酸酸中毒。所以，这一领域显然仍存在争议，且放宽二甲双胍肾脏相关限制的压力也在增大。为了对放宽二甲双胍使用的肾脏相关限制的利弊进行讨论，我们提供了一个正反观点交锋的讨论。在下面正方的叙述中，卡拉塔尔 - 扎德博士和科韦兹迪博士提出他们的观点，即尽管几乎没有证据表明二甲双胍对肾脏疾病有潜在益处，但仅考虑使用二甲双胍的人数众多以及其相关乳酸酸中毒的高死亡率，最合适的做法是避免在eGFR<45mL/min/1.73m²的人群中使用二甲双胍，或避免在有AKI高风险的人群中使用二甲双胍，无论其基础eGFR如何。在下面反方的叙述中，巴克里斯博士和莫利奇博士认为，一项非常大型分析的数据清楚地表明，应将血清肌酐替换为eGFR作为使用二甲双胍的标准，并且乳酸酸中毒的发生率仅在因各种原因脱水的eGFR降低的人群中或在接触某些导致AKI的毒素的人群中升高。否则，数据显然支持在正常情况下使用二甲双胍，直至eGFR>30mL/min/1.73m²——威廉·T·塞法卢《糖尿病护理》主编
