American Society of Hypertension Comprehensive Hypertension Center, Section of Endocrinology, Diabetes, and Metabolism, The University of Chicago Medicine, Chicago, IL
Northwestern University Feinberg School of Medicine, Chicago, IL.
Diabetes Care. 2016 Jul;39(7):1287-91. doi: 10.2337/dc15-2534.
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 preceding point narrative, 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 counterpoint narrative below, 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.
二甲双胍被认为是治疗 2 型糖尿病的一线药物，已经有超过四分之一个世纪了。像其他双胍类药物一样，二甲双胍可引起乳酸酸中毒，这种情况极其罕见，但却是致命的。在有肾功能损害的患者中，以及在那些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要高得多。因此，许多工业化国家的监管机构对二甲双胍的使用一直有严格的肾功能限制。然而，已经有数百万人使用二甲双胍多年，其中许多人的血清肌酐值在 1.5 毫克/分升或接近 1.5 毫克/分升，估计肾小球滤过率（eGFR）远低于 60 毫升/分钟/1.73 平方米，他们没有发生乳酸酸中毒。因此，在这一领域显然仍然存在争议，并且有强烈的压力要求取消对二甲双胍的肾功能限制。为了就放宽二甲双胍使用的肾功能限制的利弊进行讨论，我们提供了一个观点对观点。在前面的叙述中，Kalantar-Zadeh 博士和 Kovesdy 博士提出了他们的观点，即尽管二甲双胍在肾脏疾病方面的潜在益处证据很少，但仅考虑到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，最恰当的做法是避免在 eGFR<45 毫升/分钟/1.73 平方米的患者或在有 AKI 高风险的患者中使用二甲双胍，无论其基础 eGFR 如何。在下面的反驳叙述中，Bakris 博士和 Molitch 博士认为，一项非常大的分析数据清楚地表明，血清肌酐应该被 eGFR 取代作为使用二甲双胍的标准，并且只有在因各种原因脱水或暴露于导致 AKI 的毒素而 eGFR 降低的患者中，乳酸酸中毒的发生率才会升高。否则，数据清楚地支持在正常情况下使用二甲双胍，直至 eGFR>30 毫升/分钟/1.73 平方米-糖尿病护理主编 William T. Cefalu。
