Metformin-associated lactic acidosis may be treatable with thiamine

• Published in: Medical hypotheses Vol. 189; p. 111416
• Main Authors: Ott, Michael, Werneke, Ursula
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.08.2024
• ISSN: 0306-9877; 1532-2777; 1532-2777
• DOI: 10.1016/j.mehy.2024.111416

•Metformin and thiamine deficiency can cause lactic acidosis.•Both compete at the same hepatic transporters.•Therefore, thiamine may be a treatmentfor metformin-associated lactic acidosis. Metformin is a biguanide antidiabetic and a first-line therapy for type-2 diabetes mellitus. It is highly effective, cheap, and easily available since taken in tablet form. Metformin-associated lactic acidosis (MALA) is a serious adverse event with high mortality. It is currently treated with bicarbonate and haemodialysis. The mechanism by which metformin can precipitate lactic acidosis remains subject to debate. Lactic acidosis has also been reported in thiamine (vitamin B1) deficiency. Thiamine deficiency results in a switch from aerobic to anaerobic metabolism with accumulation of lactate. MALA and thiamine-associated lactic acidosis are usually considered separate entities. Both, thiamine and metformin are competitive substrates of the organ cation and thiamine transporters. This way, metformin could cause thiamine deficiency in liver cells. We hypothesize that MALA may be treatable with thiamine. High-dose intravenous thiamine treatment is used routinely for the treatment of Wernicke’s encephalopathy and is regarded as safe. Thiamine has been reported to have improved MALA in four cases, who had been refractory to haemodialysis. Thiamine is widely available, easy to administer, and cheap. Thiamine could already be given while waiting for dialysis. Above all, thiamine could prove life-saving in the treatment of MALA in clinical settings in which dialysis is not available.