The true incidence of fatal and nonfatal lactic acidosis associated with metformin. Metformin is recommended to be temporarily discontinued before any procedure involving use of iodinated contrast agents, such as a contrastenhanced ct scan or angiogram due to the increased risk of lactic acidosis resulting from impaired kidney function. Annual update in intensive care and emergency medicine 2011, vol 1. 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. Does highdose metformin cause lactic acidosis in type 2. Metformin should be temporarily discontinued in patients requiring surgery in volving restricted intake of food and. The lactic acidosis from metformin is primarily type b. 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.
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. Dec 17, 2019 metformin has been widely used as a firstline agent to treat type 2 diabetes mellitus. It usually occurs when a precipitating disease induces an acute renal failure and an incidental. Metformin associated lactic acidosis was characterized by elevated blood lactate levels 5 mmolliter, anion gap acidosis without evidence of ketonuria or ketonemia, an increased lactatepyruvate ratio. In the intensive care setting lactate and ph levels are regularly used as a useful predictor of poor prognosis. The major toxicity from acute or chronic biguanide use is lactic acidosis. Metformin induced lactic acidosis is rare and a diagnosis of exclusion. The first page of the pdf of this article appears above. Metformin is a safe drug when correctly used in properly selected patients. Metformin is a biguanide and the first drug of choice for blood sugar control in patients with dm type 2 because of its metabolic and cardiovascular benefits. The onset of lactic acidosis can be keep this leaflet. Metformininduced lactic acidosis with emphasis on the anion gap. Clinical pharmacokinetics of metformin pdf free download.
Though metforminassociated lactic acidosis mala is an extremely rare condition most. Background the risk of lactic acidosis during metformin therapy is linked to specific and welldocumented conditions that constitute contraindications or precautions to use of the agent. Risk of fatal and nonfatal lactic acidosis with metformin use. An overview of metformin and lactic acidosis metformin glucophage is a prescription medication licensed for the treatment of type 2 diabetes. Probably the most common mechanism by which metformin elevates blood lactate is by inducing catecholamine release in those who regulate. Metformin is thought to induce lactic acidosis and haemodynamic instability but may reduce icu mortality. The incidence of lactic acidosis with metformin is estimated to be 20 times less than with phenformin 16. What is the risk of metformin associated lactic acidosis. Xigduo xr dapagliflozin and metformin hcl extendedrelease. Metformin associated lactic acidosis precipitated by liraglutide use. A plasma metformin level taken on admission to the intensive care unit showed an elevated level at 16. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus metformin, a medication used to lower glucose levels in patients with diabetes mellitus, has long been thought to increase the risk for a metabolic disorder known as lactic acidosis. Metformin induced lactic acidosis mala is a serious illness which should identify and treat urgently. Metformin is a dimethyl biguanide oral antihyperglycemic agent.
Recent studies noted a correlation between metformin accumulation and lactic acidosis. This was thought to be the cause of her severe lactic acidosis on a background of dehydration leading to acute renal failure. 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. No warranty is given about the accuracy of the copy. We present a case of metformin associated lactic acidosis mala where drug interactions orlistat in the long term and cimetidine over a short period of time may have potentiated. Metformin induced acute pancreatitis precipitated by renal.
Pdf metformin is an oral antidiabetic drug that is widely used alone or in combination with other drugs with type 2 diabetes mellitus. Metformins role in the pathogenesis of lactic acidosis in patients with diabetes mellitus is complex, as the present case illustrates. Acidosis lactica, en relacion con insuficiencia renal aguda y metformina, tratada con hemodialisis con bicarbonatoa case of lactic acidosis related to acute renal. Due to the unpredictable nature of heart transplant, our patient received metformin within 48 hours of surgery. Severe lactic acidosis is a rare but life threatening complication of metformin, which occurs particularly in patients with renal failure. Sep 16, 2009 metformin associated lactic acidosis is a severe and potentially fatal condition that can be easily avoided. A patient with metforminassociated lactic acidosis. Diagnosis and therapy may be delayed due to nonspecific symptoms at presentation, with severe anion gap metabolic acidosis and elevated serum creatinine values being the most prominent laboratory findings. In the majority of reported cases there is a preexisting disease, most often a degree of renal impairment. The use of metformin in patients with type 2 diabetes mellitus has been associated with lactic acidosis. Steps to reduce the risk of and manage metformin associated lactic acidosis in these high risk groups are provided in the full prescribing information see dosage and administration 2. The patients known chronic kidney disease, potentially exacerbated by cardiopulmonary bypass, likely contributed to metformin induced lactic acidosis. Lactic acidosis occurs when lactate production exceeds its metabolism.
Metformin induced lactic acidosis what is the effective. Nov 21, 2012 lactic acidosis associated with metformin treatment is a rare but important adverse event, and unravelling the problem is critical. Lactic acidosis in a patient with type 2 diabetes mellitus. Lactic acidosis is a rare but serious adverse effect in patients treated with metformin. Does metformin exposure before icu stay have any impact on. Lactic acidosis and the relationship with metformin usage. Hospitalization for lactic acidosis among patients with. Impact of metformin exposure before icu stay remains controversial. There are many possible causes of lactic acidosis, and in any given patient, several causes may coexist. Treatment consists of vital function support and drug. Metformininduced lactic acidosis with emphasis on the. However, we found similar results when only adjusting for baseline egfr in active comparator. Metformin associated lactic acidosis mala is a potentially lethal condition that can result from the use of metformin in the setting of the risk factors such as renal insufficiency or hypoperfusion.
In real life, however, associated lactic acidosis has been repeatedly, although rarely, reported. We ruled out hypovolemia due to a cvp of 1415 mmhg and ischemic bowel by benign abdominal exam and normal ast, alt, amylase. It is therefore being increasingly used in higher doses. Pdf the phantom of lactic acidosis due to metformin in. The phantom of lactic acidosis due to metformin in patients.
Clarifying the relationship between metformin, acute. 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 diabetes. Metformin, a medication used to lower glucose levels in patients with diabetes mellitus, has long been thought to increase the risk for a metabolic disorder known as lactic acidosis. The high rate of severe lactic acidosis from phenformin led to the withdrawal of this drug from the us market in 1976, although it remains available in several countries. Treatment of metformin intoxication complicated by lactic. However, the most feared adverse effect is lactic acidosis. Risk factors include renal insufficiency, higher doses of metformin, and alcoholism. Lactic acidosis as a serious perioperative complication of. The reported frequency of metformin related lactic acidosis is 0. Another biguanide, phenformin, had been used since the 1950s, but was declared an imminent hazard in 1976 because of lactic acidosis 1. 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 nonfatal cases in the randomized. Lactic acidosis is a medical emergency and must be treated in the hospital.
This is the first reported case of pancreatitis caused by a therapeutic dose of metformin although in this case renal failure precipitated the metformin toxicity. Metformin associated lactic acidosis is a rare and serious complication of biguanide treatment. The phantom of lactic acidosis due to metformin in. 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. Risk of fatal and nonfatal lactic acidosis with metformin. However, the information available in patients with moderatesevere chronic kidney disease is scarce. Metformin s role in the pathogenesis of lactic acidosis in patients with diabetes mellitus is complex, as the present case illustrates. Reports of lactic acidosis attributed to metformin, 2015. Unlimited viewing of the articlechapter pdf and any associated supplements and figures. Lactic acidosis as a serious perioperative complication of antidiabetic biguanide medication with metformin you will receive an email whenever this article is corrected, updated, or cited in the literature. Llactic acidosis lla is defined by a blood llactate level of 5 mmoll. Taking metformin may increase your risk of lactic acidosis. Jan 21, 2011 metformin is a safe drug when correctly used in properly selected patients.
A case risk study of lactic acidosis risk by metformin use. Patient information for metformin 500mg tablets bp including dosage instructions and possible side effects. Background metformin therapy for type 2 diabetes mellitus has been shown to reduce total mortality rates compared with other antihyperglycemic treatments but is thought to increase the risk of lactic acidosis. Association of metformin use with risk of lactic acidosis. 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. However, we found similar results when only adjusting for baseline egfr in active comparator analyses. The major concern of many physicians is a possible risk of lactic acidosis. Research design and methods this retrospective cohort combined data from the national veterans health administration, medicare, medicaid, and the national death index.
We sought to determine whether this change was associated with increased reports of metformin associated lactic acidosis mala to the fdas adverse event reporting system faers. Objective to compare the risk of lactic acidosis hospitalization between patients treated with metformin versus sulfonylureas following development of reduced kidney function. A blood ph of mg5ml oral solution metformin hydrochloride regular exercise program because read all of this leaflet carefully before these measures can reduce the risk of you start taking this medicine because it lactic acidosis. Lactic acidosis associated with metformin in patients with moderate. This complication is very common in type 2 diabetes mellitus patients who are on metformin therapy. Apr 11, 2019 metformin amplifies the degree of lactic acidosis, but its not the sole cause of the illness. We present a case of metformin associated lactic acidosis incited by pyelonephritisinduced septic shock where use of continuous renal replacement therapy crrt led to good recovery. A 2010 study by salpeter et al found that the oral antihyperglycemic agent metformin, despite concerns to the contrary, is not associated with an increased risk for lactic acidosis compared with. The nephrologists role in metformininduced lactic acidosis. Metformin is the principal biguanide in clinical use. Lactic acidosis associated or induced by metformin. Wrexham academic unit, centre for endocrinology and diabetes, wales college of medicine, cardiff university, wrexham, uk.
Metformininduced lactic acidosis may occur in patients. Some have suggested that the link between metformin and lactic acidosis is coincidental rather than causal. Summary metformin may increase your risk of lactic acidosis. Diabetes, metformin and lactic acidosis scale 2011. We sought to determine if this change was associated with increased reports of metformin associated lactic acidosis mala to the fdas adverse event reporting system faers. Metforminassociated lactic acidosis in a patient with. Metformin accumulation was assessed in terms of the recorded measurement of metformin concentration in plasma or, if not available, by the presence of primary renal failure, i. The following describes a patient with acute renal failure and lactic acidosis as a result of concurrent treatment with metformin. We conducted a retrospective evaluation of metformin use to determine whether prescribing practices are in accord with published contraindications and precautions. Food and drug administration fda revised metformin s label to permit use in patients with mildmoderate chronic kidney disease. Metforminassociated lactic acidosis is more likely to occur in patients who acutely develop renal impairment from. Metformin intoxication with lactic acidosis, a potentially lethal condition, may develop in diabetic patients when the drug dose is inappropriate andor its clearance is reduced. Lactic acidosis is a rare 1 but serious complication of metformin therapy with a high fatality rate 2. Metformin associated lactic acidosis is a severe and potentially fatal condition that can be easily avoided.
The term metformin induced lactic acidosis refers to cases that cannot be explained by any major risk factor other than drug accumulation, usually due to renal failure. Metformin is a widely used oralantidiabetic with positive effects on metabolism. Lactic acidosis in metformintreated diabetes mellitus patients is a very rare complication, with a high mortality rate and is often associated with an. We conducted a retrospective cohort study in a 24bed french. Lactic acidosis cases often occurs in intensive care units. Metformin, one of the medicines in xigduo xr, can cause a rare but serious condition called lactic acidosis a buildup of an acid in the blood that can cause death. However, your risk for developing lactic acidosis might be much higher, depending on whether you have other risk factors for lactic. Clinically it will be impossible to differentiate this from mala. Lactic acidosis is a metabolic acidosis due to increased lactic acid levels, resulting in decreased ph in body tissues and blood. Heart transplant complicated by metformin induced lactic. Continuous renal replacement therapy for the treatment of metformin associated lactic acidosis has been documented in some case. Metformin is known to be an effective treatment for patients with type 2 diabetes mellitus. However, in some patients, specially those with comorbidities, metformin can provoke severe lactic acidosis with high morbimortality.
Risk of lactic acidosis metformin tablets may cause a. It often presents with nausea, abdominal pain, tachycardia, hypotension, and tachypnea. Treatment of metformin intoxication complicated by lactic acidosis and acute kidney injury. A case risk study of lactic acidosis risk by metformin use in type 2 diabetes mellitus tuberculosis coinfection patients. 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. Very rarely, metformin can cause a lifethreatening side effect called lactic acidosis. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Metformin is the only biguanide that is available in the u. Lactic acidosis associated with metformin treatment is a rare but important adverse event, and unravelling the problem is critical. Metformin is a commonly used treatment modality in type 2 diabetes mellitus, with a well documented side effect of lactic acidosis. If you have any possible lactic acidosis symptoms, contact your healthcare provider immediately. Patient information for metformin hydrochloride mg filmcoated tablets including dosage instructions and possible side effects.
Unlike other agents used in the treatment of type 2 diabetes mellitus, metformin has been shown to reduce mortality in obese patients. Lactic acidosis associated with metformin in patients with. Show full abstract metformin and lactic acidosis is complex, since use of the drug may be causal, coresponsible or. Complex interplay between metformin, aki and lactic acidosis. Lactic acidosis due to metformin is a fatal metabolic condition that limits its use in patients in poor clinical condition, consequently reducing the number of patients who benefit from this medication. Lactic acidosis and severe septic shock in metformin users. What is the role of metformin in the etiology of lactic acidosis. Most cases of metformin associated lactic acidosis are from patients who either had abnormal kidney function or overdosed on metformin. Salpeter ee 2010 risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. We had established that the donor cardiac function was excellent. Metformin lactic acidosis, acute renal failure and rofecoxib. In this article we highlight how high lactate levels are not an accurate predictor of mortality in deliberate metformin overdose.