Risks of Metformin in Type 2 Diabetes and Chronic Kidney Disease: Lessons Learned from Taiwanese Data.
Risks of Metformin in Type 2 Diabetes and Chronic Kidney Disease: Lessons Learned from Taiwanese Data.
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DOI：
10.1159/000450862
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发表时间：
2017
期刊：
影响因子：
2.5
通讯作者：
Kalantar-Zadeh K
中科院分区：
文献类型：
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作者：
Rhee CM;Kovesdy CP;Kalantar-Zadeh K
与其他双胍类药物一样，二甲双胍是一种抗高血糖药物，与其他抗糖尿病药物相比，低血糖倾向较低。鉴于二甲双胍对血脂、肥胖体质、心血管疾病和死亡率的有利影响，在没有禁忌症的情况下，推荐作为 2 型糖尿病的一线药物。然而，由于二甲双胍蓄积可能导致 B 型非低氧性乳酸酸中毒，特别是在肾损伤、慢性肾病和服用过量的情况下，美国食品和药物管理局 (FDA) 等监管机构对其在肾功能障碍中的使用保持了一定的限制。病例系列显示二甲双胍相关乳酸性酸中毒 (MALA) 的死亡率很高，并且排除中度至晚期肾功能不全患者的观察性研究和临床试验可能会低估 MALA 的实际发病率。 《柳叶刀内分泌学和糖尿病》杂志最近对台湾晚期糖尿病肾病患者进行的一项研究，对不限制使用二甲双胍的潜在后果提供了独特的见解，包括剂量依赖性的调整后死亡率风险增加 35%。这项及时的研究以及记录其他双胍类药物、苯乙双胍和丁双胍的毒性的历史数据表明，FDA 最近放宽了扩大二甲双胍在肾功能不全患者（即估计肾小球滤过率≥30 而不是我们推荐的≥45 ml/min/1.73m2 患者）使用的建议可能过于宽松。在这篇文章中，我们将回顾二甲双胍的使用历史；其药理学、作用机制和潜在毒性；以及随着时间的推移其使用的政策层面的变化。
Like other biguanide agents, metformin is an anti-hyperglycemic agent with lower tendency towards hypoglycemia compared to other anti-diabetic drugs. Given its favorable effects on serum lipids, obese body habitus, cardiovascular disease, and mortality, metformin is recommended as the first-line pharmacologic agent for type 2 diabetes in the absence of contraindications. However, as metformin accumulation may lead to type B non-hypoxemic lactic acidosis, especially in the setting of kidney injury, chronic kidney disease, and overdose, regulatory agencies such as the United States Food and Drug Administration (FDA) have maintained certain restrictions regarding its use in kidney dysfunction. Case series have demonstrated a high fatality rate with metformin-associated lactic acidosis (MALA), and the real-life incidence of MALA may be underestimated by observational studies and clinical trials that have excluded patients with moderate-to-advanced kidney dysfunction. A recent study of advanced diabetic kidney disease patients in Taiwan in Lancet Endocrinology and Diabetes has provided unique insight into the potential consequences of unrestricted metformin use, including a 35% higher adjusted mortality risk that was dose-dependent. This timely study, as well as historical data documenting the toxicities of other biguanides, phenformin and buformin, suggest that the recent relaxation of FDA recommendations to expand metformin use in patients with kidney dysfunction (i.e., those with estimated glomerular filtration rates ≥30 instead of our recommended ≥45 ml/min/1.73m2) may be too liberal. In this article, we will review the history of metformin use; its pharmacology, mechanism of action, and potential toxicities; and policy-level changes in its use over time.