Metformin is considered the first line oral hypoglycaemic agent for the treatment of type 2 diabetes. Its use has been related to the occurrence of lactic acidosis. Metformin is a biguanide used to lower blood glu cose levels in patients with noninsulindependent diabetes mellitus niddm. While metformin is acknowledged as having a primary role in the treatment of type 2 diabetes mellitus, many cases of lactic acidosis have been reported in metformin. Metformin is not associated with lactic acidosis in patients. Metformin associated lactic acidosis mala is a classic side effect of metformin and is known to be a severe disease with a high mortality rate.
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. Steps to reduce the risk of and manage metformin associated lactic acidosis in these high risk groups are provided see dosage and administration 2. Metformin induced lactic acidosis mala is a serious illness which should identify and treat urgently. In contrast to the conventional view, mala probably accounts for a smaller proportion of cases than either metformin. Risk of metforminassociated lactic acidosis mala is reported to be an estimated 6. Metformin associated lactic acidosis in sweden 19771991. We report three cases of prospectively identified laboratory confirmed metformin associated lactic acidosis admitted to our intensive care unit. Of 100,000 people, the incidence of lactic acidosis was 5.
Metformin is contraindicated in patients with renal or hepatic insufficiency due to the increased risk of lactic acidosis3. A case of lactic acidosis occurring in association with inappropriate and excessive metformin therapy and a high serum metformin concentration is described. Metformin is the first choice drug in type ii diabetes. Suspect mala in any patient on metformin who presents with abdominal pain, nausea and vomiting andor ams. A unique case of metforminassociated lactic acidosis hindawi. Risk of fatal and nonfatal lactic acidosis with metformin use. 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. Request pdf metforminassociated lactic acidosis introduction. Metforminassociated lactic acidosis presenting as an. Association of metformin use with risk of lactic acidosis.
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. Metformin is the firstline treatment for type 2 diabetes mellitus dm2 when diet and exercise do not result in adequate glycaemia control, especially in overweight patients. Risk factors for metformin associated lactic acidosis include renal impairment, concomitant use of certain drugs e. 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. It is recognized as a potential complication of metformin use, particularly in patients with risk factors such as renal dysfunction, liver disease, and heavy alcohol ingestion.
Metforminassociated lactic acidosis is more likely to occur. Metformin associated lactic acidosis presenting as an ischemic gut in a patient who then survived a cardiac arrest. Sep 16, 2009 metformin associated lactic acidosis is a severe and potentially fatal condition that can be easily avoided. Metformininduced lactic acidosis with emphasis on the. It was a rare entity but you explained well in short time. Nonfatal hyperkalemia in lactic acidosis due to metformin overdose. This report high lights the importance of proper patient selection, clinical and laboratory monitoring and. It often presents with nausea, abdominal pain, tachycardia, hypotension, and tachypnea. More recently it has also been used to improve fertility and weight reduction in patients with polycystic ovary syndrome. In type a lactic acidosis, treatment consists of effective management of the underlying cause, and limited evidence supports the use of sodium bicarbonate solutions to improve the ph which is associated with increased carbon dioxide generation and may reduce the calcium levels.
In the other 23 cases of metformin associated lactic acidosis reported to december 1977, renal, cardiovascular and liver disease were common. Metformin is a commonly used treatment modality in type 2 diabetes mellitus, with a well documented side effect of lactic acidosis. The phantom of lactic acidosis due to metformin in. In the last 14 years, we observed a significant increase in hospitalizations for mala to our center. Risk factors include renal insuciency, higher doses of metformin, and alcoholism. Metforminassociated lactic acidosis faisal hasan et al. Free fulltext pdf articles from hundreds of disciplines, all in one place. Although metformin has become a drug of choice for the treatment of type 2 diabetes mellitus, some patients may not receive it owing to the risk of lactic acidosis. Consuelo pedros,1,2monica avila,3ainhoa gomezlumbreras,4,5marcela manriquez,2rosa morros,4,6,7and alimarc2 study group.
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. When metformin is administered orally, approximately 40% of the dose is absorbed. The problem is extremely rare, happening in a tiny fraction of people who take the drug. However, the information available in patients with moderatesevere chronic kidney disease is scarce.
The most common symptoms following overdose include vomiting, diarrhea, abdominal pain, tachycardia, drowsiness, and, rarely, hypoglycemia or hyperglycemia. We report the outcomes of our clinical and therapeutic approach. Metformin is thought to induce lactic acidosis and haemodynamic instability but may reduce icu mortality. Her initial laboratory findings were remarkable with an arterial blood. Metforminassociated lactic acidosis was the most frequent serious adverse reaction related to metformin reported to the national authority 18. A prognostic and therapeutic study metformin associated lactic acidosis is a rare and serious complication of biguanide treatment. Metformin induced lactic acidosis what is the effective. Metformin associated lactic acidosis is not necessarily due to metformin accumulation. Role of metformin accumulation in metformin associated lactic acidosis. However, because of concern about metformin associated lactic acidosis the fda recommends that metformin not be initiated in patients with estimated glomerular filtration rates egfrs. 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. In the majority of reported cases there is a preexisting disease, most often a degree of renal impairment.
However, the best treatment strategy remains a matter of debate. Metformin associated lactic acidosis was the most frequent serious adverse reaction related to metformin reported to the national authority 18. 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. 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. Efficacy of metformin in patients with noninsulindependent diabetes mellitus. Another biguanide, phenformin, had been used since the 1950s, but was declared an imminent hazard in 1976 because of lactic acidosis 1.
Ten years retrospective analysis of patients admitted in intensive care unit for metformin associated lactic acidosis. It is unclear whether coadministration with metformin is a risk factor. What is the risk of metformin associated lactic acidosis. The authors concluded that metformin is not associated with an. If metformin associated lactic acidosis is suspected, immediately discontinue metformin. Patient on metformin develops an acute lifethreatening illness e. Metformin is the only biguanide that is available in the u. Metformin isnt associated with acidosis in diabetic. Metforminassociated lactic acidosis american board of family. Combined metforminassociated lactic acidosis and euglycemic. Lactic acidosis as a serious perioperative complication of.
Metforminassociated lactic acidosis requiring hospitalization. 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. Impact of metformin exposure before icu stay remains controversial. In the intensive care setting lactate and ph levels are regularly used as a useful predictor of poor prognosis. When it happens while taking metformin, its called mala metformin associated lactic acidosis. Therefore, it presents a diagnostic challenge that is critical to identify, particularly in patients with renal impairment at baseline. Metformin is a biguanide used to lower blood glu cose levels in patients with non insulindependent diabetes mellitus niddm. In patients with shortness of breath and clear lungs, consider metabolic acidosis with respiratory alkalis as a potential cause. 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 and lactic acidosis mitochondrial dysfunction. The treatment of mala with dialysis is controversial and is the subject of many case reports in the literature.
Does metformin exposure before icu stay have any impact on. Controversy remains whether the use of metformin is a cause or a coincidence. Though the prevalence of metformin associated lactic acidosis mala is low, mortality is high, ranging from 2550%. These conditions are associated with systemic hypoxemia, which may be caused by cardiorespiratory disease, major surgery, sepsis. May 21, 2014 lactic acidosis is the most common cause of metabolic acidosis in hospitalized patients. Lactic acidosis associated with metformin in patients with. If metformin associated lactic acidosis is suspected, immediately discontinue riomet. Hemodialysis in the treatment of lactic acidosis in diabetics treated by metformin.
While this particular patients presentation is likely multifactorial, she also has metformin associated lactic acidosis mala, secondary to metformin use during renal failure. This study aimed to determine if uninterrupted metformin administration in patients with diabetes undergoing cabg increases the risk of lactic acidosis. Metformin amplifies the degree of lactic acidosis, but its not the sole cause of the illness. Objective to investigate the role of metformin accumulation in the pathophysiology of metformin associated lactic acidosis. May 30, 2017 metformin associated lactic acidosis mala is a rare but lethal complication. Though metformin associated lactic acidosis mala is extremely rare most estimates are. In this article we highlight how high lactate levels are not an accurate predictor of mortality in deliberate metformin overdose. Role of metformin accumulation in metforminassociated lactic acidosis. Since phenformins introduction into clinical medicine, a total of 552 cases of lactic acidosis have been reported in patients taking this hypoglycemic agent. Metformin is known to be an effective treatment for patients with type 2 diabetes mellitus. Risk factors include renal insufficiency, higher doses of metformin, and alcoholism.
Although a very rare adverse effect, metformin associated lactic acidosis mala is significant because it has a high 3050 % mortality rate. Most cases of metformin associated lactic acidosis are from patients who either had abnormal kidney function or overdosed on metformin. After taking nonsteroidal antiinflammatory drugs, the patient developed vomiting, abdominal pain, diarrhea, oliguria, and lactic acidosis. It was the first antidiabetic agent that showed to reduce diabetic complications and overall mortality in overweight and obese dm2 patients. The differential diagnosis at this point should include sepsis, diabetic ketoacidosis, alcoholic ketoacidosis, toxic alcohols, and biguanide metformin toxicity.
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. The alimarc2 study is a casecontrol study to assess the association between metformin and lactic acidosis in patients with type 2 diabetes mellitus and moderatesevere chronic kidney. Some have suggested that the link between metformin and lactic acidosis is coincidental rather than causal. Metformin therapy and lactic acidosis risk overview. 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. Our results partially contradict a large cohort study investigating the association between metformin use and acidosis at low egfr. Introduction metformin is a first line oral medication for diabetes mellitus shown to decrease cardiovascular morbidity and mortality. Acute and chronic use of metformin can lead to rare complication of metformin associate lactic acidosis mala excreted unmetabolized in proximal tubules. A rare but serious condition termed metformin associated lactic acidosis mala can develop in patients with predisposing factors such as renal impairment, hepatic disease, congestive heart failure, or sepsis 8. Silvestre j, carvalho s, mendes v, coelho l, tapadinhas c, ferreira p, et al. Patients with mala will have a low ph, a highanion gap metabolic acidosis and high lactate levels. Metformin is an oral antihyperglycemic agent used to treat patients with type ii diabetes mellitus. We conducted a retrospective cohort study in a 24bed french.
May 30, 2019 the use of metformin in patients with type 2 diabetes mellitus has been associated with lactic acidosis. This drug has a renal excretion and its use requires caution in a. Metforminassociated lactic acidosis in an intensive care. Metformin treatment has been implicated as a cause of lactic acidosis because treatment with a related biguanide, phenformin, had been associated with several cases of lactic acidosis, and phenformin was removed from the us market in 1977. Metformin associated lactic acidosis mala is a wellknown serious side effect of biguanides. 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 the risk. Outcome of severe lactic acidosis associated with metformin accumulation. 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. Case files of the einstein medical center medical toxicology fellowship. Metforminassociated lactic acidosis mala is a classic side effect of metformin and is known to be a severe disease with a high mortality rate. She was confused and hypotensive with a blood pressure of 7039 mmhg.
Metformin amplies the degree of lactic acidosis, but its not the sole cause of the illness. Metforminassociated lactic acidosis mala is a potentially fatal condition characterized by an elevation in serum lactate in patients with. Metformin associated lactic acidosis junki park 9611. In 1995, the oral antihyperglycemic agent, metformin, was introduced in the united states for treating diabetes mellitus. The present report demonstrates that metforminassociated lactic acidosis is a rare but critical complication of metformin therapy of type 2 diabetes as well as in acute suicidal ingestion of. Metformin s variable contribution to lactic acidosis is reflected by use of the ambiguous term metformin.
Although a rare occurrence, metformin can cause severe, sometimes fatal, type b nonhypoxic lactic acidosis. 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. Role of metformin accumulation in metforminassociated. 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. The most significant adverse effect of metformin therapy is the development of metformin associated lactic acidosis in the susceptible patient. The aim of this article was to report a case of toe nails disorder associated with metformin use in an elderly patient with type2diabetes. Although metformin is less problematic in this regard, metformin can and does. Defronzo ra, goodman am, multicenter metformin study group. Laboratoryconfirmed metforminassociated lactic acidosis. We aimed to assess the prevalence of mala in a 16bed, universityaffiliated, intensive care unit icu, and the effect of dialysis on. 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.
Metforminassociated lactic acidosis the american journal of the. Lactic acidosis associated with metformin in patients with moderate to severe chronic kidney disease. The fda recently relaxed restrictions on metformin use in diabetic patients with moderate chronic kidney disease ckd. Metformin and lactic acidosis there are some potential adverse side effects of metformin. Metformin associated lactic acidosis by jinyu zhang, md.
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