Metformin is contraindicated in patients with renal or hepatic insufficiency due to the increased risk of lactic acidosis3. Suspect mala in any patient on metformin who presents with abdominal pain, nausea and vomiting andor ams. Metformin associated lactic acidosis was characterized by elevated blood lactate concentrations 5 mmolliter, anion gap acidosis without evidence of ketonuria or ketonemia, and an increased lactate. Treatment consists of vital function support and drug removal, mainly achieved by renal replacement therapy. Metformin associated lactic acidosis requiring hospitalization.
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. While this particular patients presentation is likely multifactorial, she also has metformin associated lactic acidosis mala, secondary to metformin use during renal failure. In the metaanalysis of comparative trials, salpeter et al. Of 100,000 people, the incidence of lactic acidosis was 5. Metforminassociated lactic acidosis requiring hospitalization. Intense exercise or convulsions can cause temporary cause lactic acidosis. Metformin use is associated with lactic acidosis, but it remains controversial as a disease entity. Nov 21, 2012 lactic acidosis associated with metformin treatment is a rare but important adverse event, and unravelling the problem is critical. The use of metformin in patients with type 2 diabetes mellitus has been associated with lactic acidosis. Metformin is a safe drug when correctly used in properly selected patients. Association of metformin use with risk of lactic acidosis. Silvestre j, carvalho s, mendes v, coelho l, tapadinhas c, ferreira p, et al. Metforminassociated lactic acidosis presenting as an. Mortality rate in socalled metforminassociated lactic acidosis.
Lactic acidosis is commonly associated with acute metformin intoxication. The prognostic value of blood ph and lactate and metformin. More recently it has also been used to improve fertility and weight reduction in patients with polycystic ovary syndrome. There is an ongoing debate on the pathogenesis of metformin associated lactic acidosis mala. Ten years retrospective analysis of patients admitted in intensive care unit for metformin associated lactic acidosis. 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. Metforminassociated lactic acidosis faisal hasan et al case.
Lactic acidosis associated with metformin in patients with. Irrespective of its underlying etiology, lactic acidosis is a life threatening condition characterized by low blood ph 5. Prognosis seems to be unrelated to plasma metformin concentration or lactate level 5. Metaanalyses and large studies have been unable to establish an epidemiological association, probably due to its low incidence rate. The reported cases of inquiries to the swedish poison information centre for metformin intoxication and lactic acidosis increased 10 times during the past decade, with 25 cases of severe lactic acidosis in 2007 and 2008. Patient on metformin develops an acute lifethreatening illness e. Education of patients with type 2 diabetes and their healthcare providers is crucial to avoid metforminassociated lactic acidosis when there is a risk of renal failure. The true incidence of fatal and nonfatal lactic acidosis associated with metformin use is not known. Introduction metformin is an oral hypoglycemic medication commonly used as a firstline agent to treat type 2 diabetes mellitus owing to its favorable safety profile. Rarely, lifethreatening complications associated with metformin treatment are seen in some patients with underlying diseases. Risk of fatal and nonfatal lactic acidosis with metformin. Food and drug administration fda has given metformin a special warning, called a black box warning, about.
Metformin is a common oral medication used for the treatment of type 2 diabetes mellitus. Renda f, mura p, finco g, ferrazin f, pani l, landoni g. These conditions are associated with systemic hypoxemia, which may be caused by cardiorespiratory disease, major surgery, sepsis. Metformin amplifies the degree of lactic acidosis, but its not the sole cause of the illness. Lactic acidosis is a rare, potentially fatal metabolic condition that can occur whenever substantial tissue hypoperfusion and hypoxia exist. In patients with shortness of breath and clear lungs, consider metabolic acidosis with respiratory alkalis as a potential cause. Oct 31, 2007 the occurrence of metformin induced lactic acidosis is exceptional when the drug is used with caution. In most of the cases, however, lactic acidosis cannot be directly attributed to metformin use but rather depends on concomitant low cardiac output, anemia, hypoxemia or liver. Metforminassociated lactic acidosis has been defined as a lactate value 5 mmoll and a bicarbonate level metformin concentrations as occur in individuals with renal impairment and a secondary event or condition that further disrupts lactate production or clearance e. The liver, kidney, heart, and skeletal muscle are the primary lactate metabolizers. Education of patients with type 2 diabetes and their healthcare providers is crucial to avoid metformin associated lactic acidosis when there is a risk of renal failure. 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.
Certain diseases can also cause the condition including. Lactic acidosis, a rare but lifethreatening complication related to metformin use, is a great concern of clinicians3. The aim of this study was to further investigate the clinical profiles and risk factors for metforminassociated lactic acidosis mala and the treatment modalities according to survival. We present a case of lactic acidosis secondary to metformin therapy with associated ketosis from vomiting. Severe lactic acidosis in patient receiving continuous ambulatory peritoneal dialysis. Jan 21, 2011 the term metformin associated lactic acidosis refers to any case of lactic acidosis that develops in a patient treated with metformin, with no further mechanistic insight.
Risk of fatal and nonfatal lactic acidosis with metformin use. Though metforminassociated lactic acidosis mala is extremely rare most. Extreme lactic acidosis type b associated with metformin. Although a very rare adverse effect, metformin associated lactic acidosis mala is significant because it has a high 3050 % mortality rate. Metforminassociated lactic acidosis has not been thoroughly characterized. Am i likely to get lactic acidosis from taking metformin. However, most cases have been reported associated with an episode of acute kidney injury aki, predominantly in intensive care units 24. Clarifying the relationship between metformin, acute kidney. Acute and chronic use of metformin can lead to rare complication of metforminassociate lactic acidosis mala excreted unmetabolized in proximal tubules stimulates anaerobic glucose metabolism in splanchnic bed increased lactate production. May 27, 2014 however, a number of anomalies were identified and after further consideration it was decided that her condition had been caused by metformin associated lactic acidosis. 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. The most common cause of lactic acidosis is severe medical illness in which blood pressure is low and too little oxygen is reaching the bodys tissues. There were 59 cases of metformin associated lactic acidosis mortality rate of 25.
Recommendations on prevention and options for treatment are also be discussed. Lactic acidosis almost never occurs with metformin exposure during routine medical care. He has been asymptomatic at subsequent followup visits. 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. 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. Lactic acidosis is rare, but serious, with a mortality up to 50% 3. The differential diagnosis at this point should include sepsis, diabetic ketoacidosis, alcoholic ketoacidosis, toxic alcohols, and biguanide metformin toxicity. 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. May 21, 2014 lactic acidosis is the most common cause of metabolic acidosis in hospitalized patients. Metforminassociated lactic acidosis is a wellknown phenomenon. Improved clinical outcomes associated with metformin in. Risk factors include renal insufficiency, higher doses of metformin, and alcoholism.
Metforminassociated lactic acidosis is a rare and serious complication of biguanide treatment. It is a type of high anion gap metabolic acidosis and is associated with various pathological processes. Lactic acidosis is a serious complication of metformin therapy and is more frequent in patients with kidney failure and other intercurrent mdtformina. 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. Janumet xr tablets combine two antidiabetic medications with complementary mechanisms of.
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. The incidence of lactic acidosis in patients on metformin therapy appears to be very low 4, 5, 6, but it can be fatal when it occurs. What is the role of metformin in the etiology of lactic acidosis. 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. Metformin and lactic acidosis there are some potential adverse side effects of metformin. Metformin associated lactic acidosis icm case summaries. Janumet xr sitagliptin and metformin tablets label fda. Although metformin has been used for over 60 years, the balance between the drugs beneficial and adverse effects is still subject to debate. 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. It is a form of metabolic acidosis, in which excessive acid accumulates due to a problem with the bodys oxidative metabolism. Respiratory alkalosis may be an early adverse event induced by metformin prior to the development of lactic acidosis. Very rarely, metformin can cause a lifethreatening side effect called lactic acidosis.
Lactate is produced by the gut, liver, and peripheral tissues during glycolysis and can accumulate during hypoxic conditions. 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. Treatment consists of vital function support and drug. It is a form of metabolic acidosis, in which excessive acid accumulates due to a problem with the bodys oxidative metabolism lactic acidosis is typically the result of an underlying acute or chronic medical.
Oct 25, 2015 although metformin associated lactic acidosis is a rare condition, with an estimated prevalence of one to five cases per 100 000 population 3, it has a reported mortality of 3050% 4. Outcome of metforminassociated lactic acidosis in type 2. Rarely, a serious condition called metforminassociated lactic acidosis mala can occur in patients with predisposing factors such as renal insufficiency, hepatic disease, congestive heart failure, or sepsis. The authors concluded that metformin is not associated with an. Risk of fatal and non fatal lactic acidosis with metformin use in type 2 diabetes mellitus. Johnson, phd 1,2 objective metformin is considered contraindicated in patients with heart failure be cause of concerns over lactic acidosis. In real life, however, associated lactic acidosis has been repeatedly, although rarely, reported. On the basis of 869 pharmacovigilance reports on mala with available data on arterial ph and lactate. It was a rare entity but you explained well in short time. Patients with mala will have a low ph, a highanion gap metabolic acidosis and high lactate levels. An unusual case of metformin associated lactic acidosis v poulose, fccp department ofmedicine, changi general hospital, 2 simei street 3, singapore 529889 introduction lactic acidosis is a wellknown, but rare complication ofbiguanide therapy. Maintain the same total daily dose of sitagliptin and metformin when changing. 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.
Though metformin associated lactic acidosis mala is extremely rare most estimates are. It usually occurs when a precipitating disease induces an acute renal failure and an incidental. Laboratoryconfirmed metforminassociated 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. The criteria we use here to define metforminassociated lactic acidosis. Lactic acidosis can occur due to metformin accumulation. Analysis of the prognostic values of blood ph and lactate and plasma metformin concentrations in severe metformin associated lactic acidosis may help to resolve the following paradox.
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. Mar 27, 2015 rarely, a serious condition called metformin associated lactic acidosis mala can occur in patients with predisposing factors such as renal insufficiency, hepatic disease, congestive heart failure, or sepsis. However, the information available in patients with moderatesevere chronic kidney disease is scarce. More recently it has also been used to improve fertility and weight reduction in patients with. Improved clinical outcomes associated with metformin in patients with diabetes and heart failure dean t. Lactic acidosis associated with metformin treatment is a rare but important adverse event, and unravelling the problem is critical. 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. There were 59 cases of metforminassociated lactic acidosis mortality rate of 25. An unusual case of metformin associated lactic acidosis.
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