The estimated mortality of metformininduced lactic acidosis is about 50% 1. Metforminassociated lactic acidosis, although very uncommon, carries a significant risk of mortality. Lactic acidosis results from overproduction of lactate, decreased metabolism of lactate, or both. However, for an individual patient, it can still be confusing sorting out the contribution of metformin to their critical illness.
However, there is still some knowledge on its occurrence. Acute and chronic use of metformin can lead to rare complication of metforminassociate lactic acidosis mala excreted unmetabolized in proximal tubules. The risk of acidosis was higher with metformin at lower gfr. Metformin induced lactic acidosis what is the effective. Summary metformin may increase your risk of lactic acidosis.
Lactic acidosis almost never occurs with metformin exposure during routine medical care. Metformin associated lacitic acidosis nyu langone health. Only 29 patients had acidosis as a diagnostic code. Metformin poisoning and lactic acidosis has always been murky. Recurrent lactic acidosis and hypoglycemia with inadvertent. Metformin associated lactic acidosis junki park 9611. If you have any possible lactic acidosis symptoms, contact your healthcare provider immediately. Lactic acidosis associated with metformin in patients with. However, use has been restricted in patients with renal impairment due to the increased risk of lactic acidosis. The incidence of lactic acidosis associated with metformin use is rather low, but this complication is still associated with a high rate of mortality 5. Lactic acidosis during current use of oral antidiabetes drugs was very rare and was associated with concurrent comorbidity.
Lactic acidosis associated with metformin treatment is a rare but important adverse event, and unravelling the problem is critical. Metformin useful but small risk of potentially fatal lactic acidosis. Metformin constitutes firstline treatment of type 2 diabetes mellitus. Most cases of metforminassociated lactic acidosis are from patients who either had abnormal kidney function or overdosed on metformin. Arguments against a causal role for metformin in lactic acidosis occurrence are the lack of correlation between plasma metformin and lactate levels, as well as between metformin plasma levels and mortality. Guidelines for the prevention, diagnosis and management of. Thus, the accumulation of metformin in the setting of renal insufficiency might be expected to precipitate lactic acidosis in. Mitochondrial encephalomyopathy lactic acidosis and stroke. It can also occur if you have a condition that causes an increased need for oxygen. At the time of its removal from the market, there had been 306 documented cases of phenforminassociated lactic acidosis 2, including 1 fatal and 2. Metformin is a safe drug when correctly used in properly selected patients. Metforminassociated lactic acidosis in a patient with. Metformin is thought to induce lactic acidosis and haemodynamic instability but may reduce icu mortality. In most cases, lactic acidosis occurs when there is kidney failure that results in metformin accumulation in the body.
Lactic acidosis may also occur in association with a number of. Lactic acidosis is the buildup of lactic acid in your blood. Rates of metforminassociated lactic acidosis is about nine per 100,000 personyears, which is similar to the background rate of lactic acidosis in the general population. These cases had a subtle onset and were accompanied by nonspecific symptoms such as malaise, myalgias, abdominal pain, respiratory distress, or increased somnolence.
The term metformininduced lactic acidosis refers to cases that cannot be explained by any major risk factor other than drug accumulation, usually due to renal failure. First, this potential event still influences treatment strategies in type 2 diabetes mellitus, particularly in the many patients at risk of kidney failure, in those presenting contraindications to metformin and in the elderly. The incidence of lactic acidosis in patients with type 2 diabetes is low but increases with age and duration of diabetes, as cardiovascular and renal causes become more prevalent. However, the information available in patients with moderatesevere chronic kidney disease is scarce. Lactate is a normal byproduct of glucose and amino acid metabolism. Metformin is associated with lactic acidosis in patients with conditions that can themselves cause lactic acidosis heart failure, hypoxia, sepsis, etc. Does metformin exposure before icu stay have any impact on.
What is the risk of metformin associated lactic acidosis. Acidosis lactica, en relacion con insuficiencia renal aguda y metformina, tratada con hemodialisis con bicarbonatoa case of lactic acidosis related to acute renal. Postmarketing cases of metforminassociated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. Very rarely, metformin can cause a lifethreatening side effect called lactic acidosis. Though metforminassociated lactic acidosis mala is extremely rare most. Metformin is the only biguanide that is available in the u. Pdf although metformin has become a drug of choice for the treatment of type 2 diabetes mellitus, some patients may not receive it owing to. Pdf metformin is an oral antidiabetic drug that is widely used alone or in combination with other drugs with type 2 diabetes mellitus. Metformin and lactic acidosis in an australian community. The exact mechanism on how metformin can cause lactic acidosis is still unclear. However, it is a key drug in the treatment of diabetes, and its coadministration with nrtis that have a high potential for hyperlactataemia i. Risk of lactic acidosis in type 2 diabetes patients using metformin. Although lactic acidosis is a widely recognized side effect of metformin, its occurrence is actually quite rare, with an incidence rate of 9 cases per 100,000 personyears of metformin exposure. Metformin induced lactic acidosis mala is a serious illness which should identify and treat urgently.
Metformininduced lactic acidosis with emphasis on the anion gap. Metforminassociated lactic acidosis litfl ccc acidbase. Lactic acidosis is a rare 1 but serious complication of metformin therapy with a high fatality rate 2. Its prevention is imperative, and we emphasise the importance of discontinuing metformin and any potentially renal toxic medications, especially angiotensin converting enzyme inhibitors and angiotensin ii receptor antagonists, in any. Lactic acidosis is a rare, but serious, metabolic complication that occurs due to metformin accumulation during treatment with metformin hydrochloride.
This is caused by a buildup of lactic acid in your blood. Hemodialysis was used to treat the acidosis and reduce the toxic concentrations. Lactic acid is a substance that can build up in your body if you are not getting enough oxygen. Metformin does not increase the risk of lactic acidosis, even when. It is presumed to have lactic acidosis as a dangerous, but rare, side effect. Mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes melas affects many parts of the body, particularly the brain and nervous system encephalo and muscles myopathy. See also metabolic acidosis, acidbase regulation, and acidbase disorders. Metformin is a useful therapeutic agent for obese noninsulin dependent diabetics and those whose glycaemia cannot be controlled by sulphonylurea monotherapy. We evaluated its influence on outcome in diabetic patients admitted in the icu and then compared two different populations based on the presence of septic shock. Risk of fatal and nonfatal lactic acidosis with metformin use in. Metformin is known to be an effective treatment for patients with type 2 diabetes mellitus. While this particular patients presentation is likely multifactorial, she also has metforminassociated lactic acidosis mala, secondary to metformin use during renal failure. This consideration is especially important in patients with severe anion gaps associated with lactic acidosis out of proportion to the patients clinical presentation. Indeed, the relationship between metformin and lactic acidosis is com.
Laboratoryconfirmed metforminassociated lactic acidosis. We aim to analyse these correlations in a large series of lactic acidosis cases recorded in the french nationwide pharmacovigilance database. Kowalski department of medical toxicology, einstein medical center, 5501 old york rd korman b14, philadelphia, pa 19141 usa. The term metformininduced lactic acidosis refers to cases that cannot be explained by any major risk factor other than drug. Metformin is recommended as the first line oral hypoglycaemia medicine for patients with type 2 diabetes in international guidelines 1. Lactic acidosis and the relationship with metformin usage. The phantom of lactic acidosis due to metformin in. There have been postmarketing cases of metforminassociated lactic acidosis, including fatal cases. Impact of metformin exposure before icu stay remains controversial. Pdf outcome of severe lactic acidosis associated with.
The risk of developing lactic acidosis is also increased with uncontrolled diabetes, serious infections, prolonged fasting or alcohol intake. Lactic acidosis caused by sandoz metformin fc is rare and has occurred mostly in people whose kidneys were not working normally. However, the causal relationship between the two events is not always proven. For years there was debate about whether metformininduced lactic acidosis exists short answer. Metformin renal impairment and risk of lactic acidosis. Although metformin is less problematic in this regard, metformin can and does. Metformin should be temporarily discontinued in patients requiring surgery in volving restricted intake of food and. Metformin is the only oral hypoglycaemic agent proved to reduce cardiovascular risk and is now recognised as the treatment of choice in overweight patients with type 2. In one case report, a 15yearold healthy girl ingested 38. Metformininduced lactic acidosis may occur in patients. Some investigators have attributed the association between metformin and lactic acidosis to the fact that type 2 diabetes is itself a risk factor for lactic acidosis, although this likely reflects the accompanying deterioration in other organ systems e. In real life, however, associated lactic acidosis has been repeatedly, although rarely, reported.
Symptoms typically begin in childhood and may include muscle weakness and pain, recurrent headaches, loss of appetite, vomiting, and seizures. In rare cases, sandoz metformin fc can cause a serious side effect called lactic acidosis. Metformin associated lactic acidosis is a severe and potentially fatal condition that can be easily avoided. The use of metformin in patients with type 2 diabetes mellitus has been associated with lactic acidosis.
While the term metforminassociated lactic acidosis is commonly used to depict all situations of lactic acidosis in metformin therapy, true metforminassociated lactic acidosis, i. Prognosis is not related to serum metformin level, it is the patients comorbidity that seems to predict survival 14. Additionally, metformin is inappropriate for patients at risk of developing lactic acidosis from another cause, as this can lead to diagnostic ambiguity. Metformin inhibits hepatic gluconeogenesis from lactate, pyruvate, alanine, resulting in additional lactate and substrate for lactate production. Dailymed metformin hydrochloride metformin tablet, film. Lactic acidosis is a medical condition characterized by the buildup of lactate especially llactate in the body, which results in an excessively low ph in the. You are advised to consult the publishers version publishers pdf if you wish to cite from it. In the medical literature, haemodialysis is recommended as the treatment of choice in metformininduced lactic acidosis 15. Another biguanide, phenformin, had been used since the 1950s, but was declared an imminent hazard in 1976 because of lactic acidosis 1. In metformin hydrochloride extendedrelease tablet treated patients with a diagnosis or strong suspicion of lactic acidosis, prompt hemodialysis is recommended to correct the acidosis and remove accumulated metformin metformin hydrochloride is dialyzable with a clearance of up to 170 mlmin under good hemodynamic conditions. Treatment of the lactic acidosis induced by metformin is based on the use of supportive general measures. We present a case of metforminassociated lactic acidosis mala where drug interactions orlistat in the long term and cimetidine over a short period of time.
When it occurs, it is fatal in approximately 50% of cases. Elevated plasma metformin concentrations as occur in individuals with renal impairment and a secondary event or condition that further disrupts lactate production or clearance e. Lactic acidosis associated with metformin in patients with moderate to severe chronic kidney disease. A recent redefinition of the condition clarifies things a bit. Some have suggested that the link between metformin and lactic acidosis is coincidental rather than causal. Case files of the einstein medical center medical toxicology fellowship kathryn t. Food and drug administration fda has given metformin a special warning, called a black box warning, about. Probably the most common mechanism by which metformin elevates blood lactate is by inducing catecholamine release in those who regulate. In the majority of reported cases there is a preexisting disease, most often a degree of renal impairment. Lactic acidosis with metformin is very rare, but there are certain people who are at an increased risk for lactic acidosis and should not take metformin. Metformin tablets may cause a very rare, but very serious side effect called lactic acidosis, particularly if your kidneys are not working properly. The onset of metforminassociated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain.