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. Pdf the phantom of lactic acidosis due to metformin in. Metformin is the principal biguanide in clinical use. What is the risk of metformin associated lactic acidosis. Metforminassociated lactic acidosis in a patient with. There are many possible causes of lactic acidosis, and in any given patient, several causes may coexist. 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. Lactic acidosis as a serious perioperative complication of. 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. Due to the unpredictable nature of heart transplant, our patient received metformin within 48 hours of surgery. The use of metformin in patients with type 2 diabetes mellitus has been associated with lactic acidosis. Summary metformin may increase your risk of lactic acidosis.
Lactic acidosis associated with metformin in patients with moderate. The patients known chronic kidney disease, potentially exacerbated by cardiopulmonary bypass, likely contributed to metformin induced lactic acidosis. Metformin induced acute pancreatitis precipitated by renal. Lactic acidosis is a medical emergency and must be treated in the hospital. Unlike other agents used in the treatment of type 2 diabetes mellitus, metformin has been shown to reduce mortality in obese patients. Llactic acidosis lla is defined by a blood llactate level of 5 mmoll.
Lactic acidosis occurs when lactate production exceeds its metabolism. What is the role of metformin in the etiology of lactic acidosis. The phantom of lactic acidosis due to metformin in patients. Metformin induced lactic acidosis is rare and a diagnosis of exclusion. When lactic acidosis is diagnosed in a patient treated with metformin, but metformin overdose is not detected, the term metformin associated lactic acidosis mala better describes the condition. Treatment consists of vital function support and drug. Does metformin exposure before icu stay have any impact on. Lactic acidosis associated with metformin treatment is a rare but important adverse event, and unravelling the problem is critical. Research design and methods this retrospective cohort combined data from the national veterans health administration, medicare, medicaid, and the national death index.
Lactic acidosis and the relationship with metformin usage. Patient information for metformin hydrochloride mg filmcoated tablets including dosage instructions and possible side effects. Severe lactic acidosis is a rare but life threatening complication of metformin, which occurs particularly in patients with renal failure. The lactic acidosis from metformin is primarily type b. Metformin is a commonly used treatment modality in type 2 diabetes mellitus, with a well documented side effect of lactic acidosis. Association of metformin use with risk of lactic acidosis. Treatment of metformin intoxication complicated by lactic. Lactic acidosis and severe septic shock in metformin users. Diabetes, metformin and lactic acidosis scale 2011. Risk of lactic acidosis metformin tablets may cause a. Lactic acidosis is a rare but serious adverse effect in patients treated with metformin. Cureus metforminassociated lactic acidosis successfully. Lactic acidosis is a metabolic acidosis due to increased lactic acid levels, resulting in decreased ph in body tissues and blood. 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 associated or induced by metformin. 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. Probably the most common mechanism by which metformin elevates blood lactate is by inducing catecholamine release in those who regulate. Metformin s role in the pathogenesis of lactic acidosis in patients with diabetes mellitus is complex, as the present case illustrates. Metformin is a widely used oralantidiabetic with positive effects on metabolism. 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.
Food and drug administration fda revised metformin s label to permit use in patients with mildmoderate chronic kidney disease. Nov 21, 2012 lactic acidosis associated with metformin treatment is a rare but important adverse event, and unravelling the problem is critical. Risk of fatal and nonfatal lactic acidosis with metformin. The incidence of lactic acidosis with metformin is estimated to be 20 times less than with phenformin 16.
Unlimited viewing of the articlechapter pdf and any associated supplements and figures. Lactic acidosis in metformintreated diabetes mellitus patients is a very rare complication, with a high mortality rate and is often associated with an. Does highdose metformin cause lactic acidosis in type 2. 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. Some have suggested that the link between metformin and lactic acidosis is coincidental rather than causal. The onset of lactic acidosis can be keep this leaflet. Metformin associated lactic acidosis can occur acutely in an overdose but typically has a more gradual onset in patients with hepatic or renal dysfunction due to decreased excretion. Metformins role in the pathogenesis of lactic acidosis in patients with diabetes mellitus is complex, as the present case illustrates. In the majority of reported cases there is a preexisting disease, most often a degree of renal impairment. 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. A case risk study of lactic acidosis risk by metformin use. However, your risk for developing lactic acidosis might be much higher, depending on whether you have other risk factors for lactic.
Metformin induced lactic acidosis mala is a serious illness which should identify and treat urgently. Lactic acidosis associated with metformin in patients with. In the intensive care setting lactate and ph levels are regularly used as a useful predictor of poor prognosis. Show full abstract metformin and lactic acidosis is complex, since use of the drug may be causal, coresponsible or. In this article we highlight how high lactate levels are not an accurate predictor of mortality in deliberate metformin overdose. A plasma metformin level taken on admission to the intensive care unit showed an elevated level at 16. Metformin is a dimethyl biguanide oral antihyperglycemic agent. Dec 17, 2019 metformin has been widely used as a firstline agent to treat type 2 diabetes mellitus.
Sep 16, 2009 metformin associated lactic acidosis is a severe and potentially fatal condition that can be easily avoided. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. 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. 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. Patient information for metformin 500mg tablets bp including dosage instructions and possible side effects. Metformin associated lactic acidosis precipitated by liraglutide use. Metformin associated lactic acidosis is a severe and potentially fatal condition that can be easily avoided. Very rarely, metformin can cause a lifethreatening side effect called lactic acidosis.
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. However, in some patients, specially those with comorbidities, metformin can provoke severe lactic acidosis with high morbimortality. 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. Treatment of metformin intoxication complicated by lactic acidosis and acute kidney injury. We ruled out hypovolemia due to a cvp of 1415 mmhg and ischemic bowel by benign abdominal exam and normal ast, alt, amylase. 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. We had established that the donor cardiac function was excellent. Lactic acidosis induced by metformin is typical, but a rare form of type b lactic acidosis, termed metformin induced lactic acidosis mila. Xigduo xr dapagliflozin and metformin hcl extendedrelease. Jan 21, 2011 metformin is a safe drug when correctly used in properly selected patients.
Metformin is thought to induce lactic acidosis and haemodynamic instability but may reduce icu mortality. 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. This complication is very common in type 2 diabetes mellitus patients who are on metformin therapy. A patient with metforminassociated lactic acidosis. This was thought to be the cause of her severe lactic acidosis on a background of dehydration leading to acute renal failure. 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. Most cases of metformin associated lactic acidosis are from patients who either had abnormal kidney function or overdosed on metformin. 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. Another biguanide, phenformin, had been used since the 1950s, but was declared an imminent hazard in 1976 because of lactic acidosis 1. Annual update in intensive care and emergency medicine 2011, vol 1. An overview of metformin and lactic acidosis metformin glucophage is a prescription medication licensed for the treatment of type 2 diabetes. The major concern of many physicians is a possible risk of lactic acidosis. 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. Wrexham academic unit, centre for endocrinology and diabetes, wales college of medicine, cardiff university, wrexham, uk.
The reported frequency of metformin related lactic acidosis is 0. Lactic acidosis is a rare 1 but serious complication of metformin therapy with a high fatality rate 2. 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. Metformininduced lactic acidosis may occur in patients. 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. 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 is the only biguanide that is available in the u.
We conducted a retrospective cohort study in a 24bed french. It is therefore being increasingly used in higher doses. Lactic acidosis cases often occurs in intensive care units. Metformin lactic acidosis, acute renal failure and rofecoxib. It often presents with nausea, abdominal pain, tachycardia, hypotension, and tachypnea. However, we found similar results when only adjusting for baseline egfr in active comparator. Salpeter ee 2010 risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus.
Metformin should be temporarily discontinued in patients requiring surgery in volving restricted intake of food and. Acidosis lactica, en relacion con insuficiencia renal aguda y metformina, tratada con hemodialisis con bicarbonatoa case of lactic acidosis related to acute renal. Third, if the effect of metformin use on lactic acidosis were mediated by decline in egfr, the use of timedependent egfr in our analyses could bias results to the null. 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. Lactic acidosis in a patient with type 2 diabetes mellitus. 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 associated lactic acidosis is a rare and serious complication of biguanide treatment. Apr 11, 2019 metformin amplifies the degree of lactic acidosis, but its not the sole cause of the illness. 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. The nephrologists role in metformininduced lactic acidosis. Clarifying the relationship between metformin, acute. Risk factors include renal insufficiency, higher doses of metformin, and alcoholism. Heart transplant complicated by metformin induced lactic.
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. Risk of fatal and nonfatal lactic acidosis with metformin use. A case risk study of lactic acidosis risk by metformin use in type 2 diabetes mellitus tuberculosis coinfection patients. In real life, however, associated lactic acidosis has been repeatedly, although rarely, reported. 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. Metformininduced lactic acidosis with emphasis on the anion gap. 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. However, we found similar results when only adjusting for baseline egfr in active comparator analyses. Taking metformin may increase your risk of lactic acidosis. If you have any possible lactic acidosis symptoms, contact your healthcare provider immediately. 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.
Reports of lactic acidosis attributed to metformin, 2015. We conducted a retrospective evaluation of metformin use to determine whether prescribing practices are in accord with published contraindications and precautions. Objective to compare the risk of lactic acidosis hospitalization between patients treated with metformin versus sulfonylureas following development of reduced kidney function. Pdf metformin is an oral antidiabetic drug that is widely used alone or in combination with other drugs with type 2 diabetes mellitus.
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. Clinically it will be impossible to differentiate this from mala. 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. Recent studies noted a correlation between metformin accumulation and lactic acidosis. It usually occurs when a precipitating disease induces an acute renal failure and an incidental. No warranty is given about the accuracy of the copy. The phantom of lactic acidosis due to metformin in. 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.
Metformin is a safe drug when correctly used in properly selected patients. However, the information available in patients with moderatesevere chronic kidney disease is scarce. Complex interplay between metformin, aki and lactic acidosis. Hospitalization for lactic acidosis among patients with. However, the most feared adverse effect is lactic acidosis. 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. Continuous renal replacement therapy for the treatment of metformin associated lactic acidosis has been documented in some case.
Impact of metformin exposure before icu stay remains controversial. Metformin is known to be an effective treatment for patients with type 2 diabetes mellitus. Metforminassociated lactic acidosis is more likely to occur in patients who acutely develop renal impairment from. The true incidence of fatal and nonfatal lactic acidosis associated with metformin. Clinical pharmacokinetics of metformin pdf free download. Metformin induced lactic acidosis what is the effective. The following describes a patient with acute renal failure and lactic acidosis as a result of concurrent treatment with metformin. Metformininduced lactic acidosis with emphasis on the. Though metforminassociated lactic acidosis mala is an extremely rare condition most. 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 with metformin is very rare, but there are certain people who are at an increased risk for lactic acidosis and should not take metformin.