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Metformin is one of many medications that can cause lactic acidosis. Symptoms of lactic acidosis include nausea, vomiting and weakness. Fortunately, the risk of lactic acidosis is a rare side ...
Lactic acidosis is commonly found in people who are unwell, such as those with severe heart and/or lung disease, a severe infection with sepsis, the systemic inflammatory response syndrome due to another cause, severe physical trauma, or severe depletion of body fluids. [3]
Others include peripheral neuropathy (numbness in the fingers and toes) and pancreatitis (inflammation of the pancreas), with the most severe being lactic acidosis, in which a build-up of lactic acid in the tissues of the body leads to loss of energy, organ failure, and eventually death. [3]
One of the most serious (but quite rare) risks of metformin is lactic acidosis, the buildup of lactic acid. Lactic acidosis can be fatal, and the early signs are sometimes easy to miss.
Because metformin decreases liver uptake of lactate, any condition that may precipitate lactic acidosis is a contraindication. Common causes include alcoholism (due to depletion of NAD+ stores), heart failure, and respiratory disease (due to inadequate tissue oxygenation); the most common cause is kidney disease. [95]
The accumulation of these organic acids can cause an acidosis with an increased anion gap as well as a decreased buffering capacity of the body. [9] Salicylate toxicity also causes an uncoupling of oxidative phosphorylation and a decrease in citric acid cycle activity in the mitochondria. [9]
The drug metformin can cause lactic acidosis in patients with kidney failure because metformin inhibits the hepatic gluconeogenesis of the Cori cycle, particularly the mitochondrial respiratory chain complex 1. [8] The buildup of lactate and its substrates for lactate production, pyruvate and alanine, lead to excess lactate. [9]
The most important and serious side effect is lactic acidosis, therefore metformin is contraindicated in advanced chronic kidney disease. Kidney function should be assessed before starting metformin. Phenformin and buformin are more prone to cause acidosis than metformin; therefore they have been practically replaced by it.