Metformin, plasma glucose and free fatty acids in type ii diabetic outpatients. This study is a matched casecontrol analysis concerning the type 2 diabetes population from grenoble hospital university. Increased use of metformin and lactic acidosis introduction metformin e. More recently it has also been used to improve fertility and weight reduction in patients with. Nov 21, 2012 lactic acidosis associated with metformin treatment is a rare but important adverse event, and unravelling the problem is critical. Lactic acidosis almost never occurs with metformin exposure during routine medical care. However, as demonstrated in this case, extreme lactic acidosis may develop in patients on therapeutic doses of metformin in the setting of acute renal failure induced by a prolonged episode of dehydration.
At the time of its removal from the market, there had been 306 documented cases of phenformin associated lactic acidosis 2, including 1 fatal and 2 nonfatal cases in the randomized. Suspect mala in any patient on metformin who presents with abdominal pain, nausea and vomiting andor ams. Severe lactic acidosis is certainly not specific to mala and is associated with many other lifethreatening conditions such as ischemic gut and sepsis as well as other toxic exposures such as cyanide, carbon monoxide, hydrogen sulfide, etc. This article discusses the case of a 68yearold emergency department patient with hypoglycaemia, hypotension. Metforminassociated lactic acidosis requiring hospitalization. Unlimited viewing of the articlechapter pdf and any associated supplements and figures. Should dialysis be offered in all cases of metforminassociated lactic acidosis. Metformin and lactic acidosis there are some potential adverse side effects of metformin. Although a very rare adverse effect, metformin associated lactic acidosis mala is significant because it has a high 3050 % mortality rate.
Metformin, marketed under the trade name glucophage among others, is the firstline medication for the treatment of type 2 diabetes, particularly in people who are overweight. In patients with shortness of breath and clear lungs, consider metabolic acidosis with respiratory alkalis as a potential cause. Correlation between plasma metformin concentration and lactate levels. What is the role of metformin in the etiology of lactic acidosis. Metformin is commonly used in diabetes mellitus type 2, with lactic acidosis being a rare but potentially fatal complication of this therapy. Oct 11, 2010 age p 001, acute renal failure p 0015 and sepsis p 0005 were associated with mortality. Rare cases of metformin associated lactic acidosis caused by the accumulation of the drug in patients with renal dysfunction have been described, although a detailed time course of the resulting metabolic derangements has not been reported. Treatment consists of vital function support and drug. A cappuccino with claudio ronco article video and free access to article.
It is a type of high anion gap metabolic acidosis and is associated with various pathological processes. Rates of metformin associated lactic acidosis is about nine per 100,000 personyears, which is similar to the background rate of lactic acidosis in the general population. Therefore, it presents a diagnostic challenge that is critical to identify, particularly in patients with renal impairment at baseline. Mortality rate in socalled metforminassociated lactic acidosis. Metformin and contrast media william chui metformin is an oral antihyperglycaemic agent commonly used in noninsulin dependent type 2 diabetes mellitus. The liver, kidney, heart, and skeletal muscle are the primary lactate metabolizers, while.
Metformin, renal function and lactic acidosis, a population based study the use of metformin is limite the use of metformin is limited by impaired renal function and fear of lactic acidosis. The authors concluded that metformin is not associated with an. Patients with these conditions may be at increased risk for the development of lactic acidosis, which is a rare but serious metabolic complication associated with metformin accumulation in plasma usually at levels exceeding 5 mcgml. Department of emergency medicine, north shore university health systems, evanston, illinois. 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. It was first introduced ain the 1950s along with phenformin. Oct 31, 2007 the occurrence of metformin induced lactic acidosis is exceptional when the drug is used with caution. In the city of malmouml, population 300 000, all patients who had filled three prescriptions of metformin for each year 20082009 were identified and. Combined metforminassociated lactic acidosis and euglycemic. We conducted a prospective observational study of metforminassociated aki cases during four years. Lactic acidosis is a medical condition characterized by the buildup of lactate especially llactate in the body, with formation of an excessively low ph in the bloodstream.
Metformin and lactic acidosis british journal of anaesthesia. Increased use of metformin and lactic acidosis introduction. Pdf although metformin has become a drug of choice for the treatment of type 2 diabetes mellitus, some patients may. The liver, kidney, heart, and skeletal muscle are the primary lactate metabolizers. Am i likely to get lactic acidosis from taking metformin. Metforminassociated acute kidney injury and 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. This study was designed to document the characteristics and prognostic factors of intentional and incidental metformin overdose and to determine the optimal duration of hd. Association of metformin use with risk of lactic acidosis. Metformin associated lactic acidosis is a potentially fatal yet rare diagnosis. Renda f, mura p, finco g, ferrazin f, pani l, landoni g. Metformin associated lactic acidosis mala may complicate metformin therapy, particularly if metformin accumulates due to renal dysfunction. Metformin is the only biguanide that is available in the u. Lactic acidosis is rare, but serious, with a mortality up to 50% 3.
Ahmed abuzaid, mbbch 1 and mahmoud abu hazeem, mbbs 1. Patients with mala will have a low ph, a highanion gap metabolic acidosis and high lactate levels. In this article we highlight how high lactate levels are not an accurate predictor of mortality in deliberate metformin overdose. Risk of metforminassociated lactic acidosis mala is reported to be an estimated 6. An unusual case of metformin associated lactic acidosisv poulose, fccp department ofmedicine, changi general hospital, 2 simei street 3, singapore 529889 introduction lactic acidosis is a wellknown, but rare complication ofbiguanide therapy. Should dialysis be offered in all cases of metforminassociated lactic. Association between metformin use and risk of lactic acidosis or. His medications list included metformin and glipizide. Lactic acidosis is commonly associated with acute metformin intoxication. Metforminassociated lactic acidosis is a rare and serious complication of biguanide treatment.
Lactic acidosis a buildup of lactic acid in the body is a rare complication of taking metformin glucophage, fortamet, but you could be at an increased risk for this condition if youre dehydrated or if you drink large amounts of alcohol. It is also used in the treatment of polycystic ovary syndrome. Pietro addamo and dr simona polemi illustrate metabolic and pathophysiological pathways that lead to lactic acidosis caused by metformin. In propensity scorematched cohorts within strata of egfr, metformin use was associated with similar risk of acidosis compared with use of alternative hypoglycemic medications at egfr 45 to 59 mlmin1. Metforminassociated lactic acidosis was the most frequent serious adverse reaction related to metformin reported to the national authority 18. The differential diagnosis at this point should include sepsis, diabetic ketoacidosis, alcoholic ketoacidosis, toxic alcohols, and biguanide metformin toxicity. Risk of fatal and nonfatal lactic acidosis with metformin use in. Risk factors include renal insufficiency, higher doses of metformin, and alcoholism. Liraglutide can precipitate mala if taking metformin concomitantly as it. Phenformin was available in the united states until 1977 when the fda withdrew it due to the frequency of lactic acidosis.
We present a case of lactic acidosis secondary to metformin therapy with associated ketosis from vomiting. Diabetes, metformin and lactic acidosis scale 2011. Can acute overdose of metformin lead to lactic acidosis. Another biguanide, phenformin, had been used since the 1950s, but was declared an imminent hazard in 1976 because of lactic acidosis 1. Treatment of metformin intoxication complicated by lactic. Metforminassociated lactic acidosis deborah briggs lecturer in critical care, university of hull deborah briggs presents a case study involving a woman with severe ph imbalance caused by a drug taken to manage type 2 diabetes. Lactic acidosis in metformintreated patients springerlink. Metforminassociated lactic acidosis has been defined as a lactate value 5 mmoll and a bicarbonate level download options will not persist. Lactic acidosis unrelated to metformin is a relatively common occurrence among the critically ill and usually arises as a result of tissue hypoxia consequent on the inadequate perfusion associated. Metformin associated lactic acidosis by jinyu zhang, md. There were 59 cases of metformin associated lactic acidosis mortality rate of 25. However, your risk for developing lactic acidosis might be much higher, depending on whether you have other risk factors for lactic acidosis.
Nov 27, 2012 the antidiabetic drug metformin has been associated in a small number of patients with lactic acidosis, a serious condition with a poor prognosis. Lactic acidosis is a serious reaction to metformin, and hemodialysis the treatment of choice should be done urgently to. Data were collected from 49 metformintreated patients with lactic acidosis arterial lactate level. Jan 21, 2011 metformin is a safe drug when correctly used in properly selected patients. 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. While this particular patients presentation is likely multifactorial, she also has metforminassociated lactic acidosis mala, secondary to metformin use during renal failure.
Metformin is a commonly used treatment modality in type 2 diabetes mellitus, with a well documented side effect of lactic acidosis. Rare cases of metforminassociated lactic acidosis caused by the accumulation of the drug in patients with renal dysfunction have been described, although a detailed time course of the resulting metabolic derangements has not been reported. Since february 1999 according to the practice guidelines of the dutch college of general practitioners 1, metformin is the drug of first choice for the treatment of obese patients with. There were 59 cases of metforminassociated lactic acidosis mortality rate of 25. Though the prevalence of metformin associated lactic acidosis mala is low, mortality is high, ranging from 2550%. Please click confirm if you are happy to lose these search results. Lactic acidosis is a lifethreatening condition that is fatal in about 50 percent of cases and is caused by too much lactate in the blood and low blood ph. A case of lactic acidosis occurring in association with inappropriate and excessive metformin therapy and a high serum metformin concentration is described. In 1995, the oral antihyperglycemic agent, metformin, was introduced in the united states for treating diabetes mellitus. Metforminassociated lactic acidosis undergoing renal. 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. Very rarely, metformin can cause a lifethreatening side effect called lactic acidosis. Metforminassociated lactic acidosis mala is a severe complication of drug administration. 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.
It usually occurs when a precipitating disease induces an acute renal failure and an incidental. 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. Extreme lactic acidosis type b associated with metformin. Case was a 70yearold man with metforminassociated lactic acidosis mala. More recently it has also been used to improve fertility and weight reduction in patients with polycystic ovary syndrome. Age p 001, acute renal failure p 0015 and sepsis p 0005 were associated with mortality. A 76yearold white male, with type 2 diabetes mellitus dm, presented with three days history of confusion and difficulty finding words which started after aggressive vomiting of two days duration. Previous renal function, clinical data, and outcomes. Liraglutide can precipitate mala if taking metformin concomitantly as it often causes nausea and vomiting, which can lead. An unusual case of metformin associated lactic acidosis.
Metforminassociated lactic acidosis mala is usually described in the setting of chronic therapeutic dosing in a patient with a c0morbidity or contraindication to use of the drug, such as renal failure. The phantom of lactic acidosis due to metformin in. Most cases of metformin associated lactic acidosis are from patients who either had abnormal kidney function or overdosed on metformin. Metformin, renal function and lactic acidosis, a population.
Case was a 70yearold man with metformin associated lactic acidosis mala. Outcome of severe lactic acidosis associated with metformin. 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. Though the prevalence of metforminassociated lactic acidosis mala is low, mortality is high, ranging from 2550%. Metformin should also not be administered to patients with acute or chronic metabolic acidosis. In the intensive care setting lactate and ph levels are regularly used as a useful predictor of poor prognosis. On examination, patient was alert, awake, but disoriented to place and time. It usually occurs when a precipitating disease induces an acute renal failure and an incidental overdose. Intuitively, it would be supposed that the chance of surviving metformin associated lactic acidosis mala would be related to the severity of the lactate acidosis i. Sep 16, 2009 dehydration in patients taking metformin can lead to metformin associated lactic acidosis, a potentially fatal condition metformin, a dimethylbiguanide, is a widely used oral antihyperglycaemic drug used in the long term treatment of type 2 diabetes mellitus.
Metforminassociated lactic acidosis is a potentially fatal yet rare diagnosis. Prompt recognition of even subtle symptoms can reduce mortality and preserve homeostasis. Clinically it will be impossible to differentiate this from mala. Lactic acidosis occurs in association with acute illness particularly in diabetes. Metformin amplifies the degree of lactic acidosis, but its not the sole cause of the illness. Metformin associated lactic acidosis is a rare and serious complication of biguanide treatment. Food and drug administration fda has given metformin a special warning, called a black box warning, about. Ten years retrospective analysis of patients admitted in intensive care unit for metformin associated 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. Oct 30, 2015 lactic acidosis is typically defined as a ph less than 7. Severe lactic acidosis in patient receiving continuous ambulatory peritoneal dialysis.
Presumed metformin associated lactic acidosis with normal. Introduction metformin is a first line oral medication for diabetes mellitus shown to decrease cardiovascular morbidity and mortality. Of 100,000 people, the incidence of lactic acidosis was 5. Metformin is the preferred oral antidiabetic agent for type 2 diabetes. In the other 23 cases of metformin associated lactic acidosis reported to december 1977, renal, cardiovascular and liver disease were common. Venous blood gas sampling showed a lactic acidosis ph 7. Lactic acidosis is described as a rare complication, usually during an acute kidney injury aki. A 70yearold female with diabetes mellitus type ii and a oneweek old left frontal. Lactic acidosis associated with metformin treatment is a rare but important adverse event, and unravelling the problem is critical. However, because of lack of data, the prognostic significance of hyperlactataemia in metformintreated patients is not known. Lactate is produced by the gut, liver, and peripheral tissues during glycolysis and can accumulate during hypoxic conditions. Presumed metformin associated lactic acidosis with normal kidney function. Metformin is a safe drug when correctly used in properly selected patients.
This showed rightsided free fluid in the abdomen and inflammatory. In real life, however, associated lactic acidosis has been repeatedly, although rarely, reported. However, your risk for developing lactic acidosis might be much higher, depending on. Here we describe a rare case of metformin associated lactic acidosis. It is a form of metabolic acidosis, in which excessive acid accumulates due to a problem with the bodys oxidative metabolism. Irrespective of its underlying etiology, lactic acidosis is a life threatening condition characterized by low blood ph 5. 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. Dehydration in patients taking metformin can lead to metformin associated lactic acidosis, a potentially fatal condition metformin, a dimethylbiguanide, is a widely used oral antihyperglycaemic drug used in the long term treatment of type 2 diabetes mellitus.
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