University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Children's Hospital Colorado, Aurora, CO, USA.
J Intensive Care Med. 2019 Nov-Dec;34(11-12):863-876. doi: 10.1177/0885066618793385. Epub 2018 Aug 21.
In the 1920s, guanidine, the active component of , was shown to lower glucose levels and used to synthesize several antidiabetic compounds. Metformin (1,1 dimethylbiguanide) is the most well-known and currently the only marketed biguanide in the United States, United Kingdom, Canada, and Australia for the treatment of non-insulin-dependent diabetes mellitus. Although phenformin was removed from the US market in the 1970s, it is still available around the world and can be found in unregulated herbal supplements. Adverse events associated with therapeutic use of biguanides include gastrointestinal upset, vitamin B deficiency, and hemolytic anemia. Although the incidence is low, metformin toxicity can lead to hyperlactatemia and metabolic acidosis. Since metformin is predominantly eliminated from the body by the kidneys, toxicity can occur when metformin accumulates due to poor clearance from renal insufficiency or in the overdose setting. The dominant source of metabolic acidosis associated with hyperlactatemia in metformin toxicity is the rapid cytosolic adenosine triphosphate (ATP) turnover when complex I is inhibited and oxidative phosphorylation cannot adequately recycle the vast quantity of H+ from ATP hydrolysis. Although metabolic acidosis and hyperlactatemia are markers of metformin toxicity, the degree of hyperlactatemia and severity of acidemia have not been shown to be of prognostic value. Regardless of the etiology of toxicity, treatment should include supportive care and consideration for adjunct therapies such as gastrointestinal decontamination, glucose and insulin, alkalinization, extracorporeal techniques to reduce metformin body burden, and metabolic rescue.
在上世纪 20 年代，胍乙啶，即苯乙双胍的有效成分，被证实能降低血糖水平，并被用于合成几种抗糖尿病化合物。二甲双胍（1,1-二甲基双胍）是目前美国、英国、加拿大和澳大利亚唯一上市的双胍类药物，用于治疗非胰岛素依赖型糖尿病。尽管苯乙双胍在 20 世纪 70 年代已从美国市场撤出，但它在全球范围内仍有供应，并可在不受监管的草药补充剂中找到。与双胍类药物治疗相关的不良事件包括胃肠道不适、维生素 B 缺乏和溶血性贫血。虽然发病率较低，但二甲双胍毒性可导致高乳酸血症和代谢性酸中毒。由于二甲双胍主要通过肾脏从体内清除，因此在肾功能不全或过量用药时，由于清除不良而导致二甲双胍蓄积，可能会发生毒性。与二甲双胍毒性相关的高乳酸血症代谢性酸中毒的主要来源是当复合物 I 被抑制时，细胞溶质三磷酸腺苷 (ATP) 快速周转，而氧化磷酸化无法从 ATP 水解中有效回收大量 H+。尽管代谢性酸中毒和高乳酸血症是二甲双胍毒性的标志物，但高乳酸血症的程度和酸中毒的严重程度尚未显示出具有预后价值。无论毒性的病因如何，治疗都应包括支持性护理，并考虑采用辅助治疗，如胃肠道去污、葡萄糖和胰岛素、碱化、体外技术以减少二甲双胍的体内负担以及代谢挽救。
