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. Starting with a case report of a 62yearold woman presenting with abdominal pain, we bring this complication to attention, describing its pathogenesis and its management. 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. Metforminassociated lactic acidosis mala has a mortality of around 30%2 and the underlying cause must also be. Recent studies noted a correlation between metformin accumulation and lactic acidosis. Suspect mala in any patient on metformin who presents with abdominal pain, nausea and vomiting andor ams. Metformin amplifies the degree of lactic acidosis, but its not the sole cause of the illness. 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. A unique case of metforminassociated lactic acidosis hindawi. Metformin associated lactic acidosis mala is a rare but potentially lifethreatening adverse effect of metformin use in patients with type 2 diabetes, the risk for which is increased in patients with acute kidney injury.
Though the prevalence of metformin associated lactic acidosis mala is low, mortality is high, ranging from 2550%. Management of metforminassociated lactic acidosis with sled. Metforminassociated lactic acidosis mala is a rare complication among patients who are diabetic, commonly presenting with nonspecific findings, and developing mostly among those with other risk factors for lactic acidosis. Although metformin is generally safe, metforminassociated. In real life, however, associated lactic acidosis has been repeatedly, although rarely, reported.
Metformin is a very potent antidiabetic drug that has become the drug of choice for the treatment of type 2 diabetes. Early diagnosis is essential to start an early treatment, which often has favorable results. Symptoms included malaise, myalgias, respiratory distress, somnolence, and abdominal pain. A patient with metforminassociated lactic acidosis. Feeling blue with metforminassociated lactic acidosis bmj. This buildup of acid causes an imbalance in the bodys. Metforminassociated lactic acidosis mala is a potentially fatal condition characterized by an elevation in serum lactate in patients with. In lactic acidosis, the liver is unable to remove excess acid. Apr 17, 2017 following an analysis of how cases of so. Lactic acidosis as a serious perioperative complication of. Steps to reduce the risk of and manage metforminassociated lactic acidosis in these high risk groups are provided in the full prescribing information. 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.
Metformin is widely used as a firstline therapy for type 2 diabetes mellitus t2dm. Pdf metformin has been used in europe since the 1970s to treat type 2 diabetes mellitus t2dm. 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. Jan 22, 2016 metformin mf accumulation during acute kidney injury is associated with high anion gap lactic acidosis type b mfassociated lactic acidosis, mala, a serious medical condition leading to high mortality. We present a case of metforminassociated lactic acidosis incited by pyelonephritisinduced septic shock where use of continuous renal replacement therapy crrt led to good recovery. Metformin associated lactic acidosis by jinyu zhang, md. Retrospective study of plasma lactate levels before and 3 months after rygb surgery in patients with type 2 diabetes. In the majority of reported cases there is a preexisting disease, most often a degree of renal impairment. Laboratory abnormalities included elevated blood lactate levels, anion gap acidosis, an increased lactatepyruvate ratio, and.
Metforminassociated lactic acidosis mla is a rare but fatal complication. Metformins role in the pathogenesis of lactic acidosis in patients with diabetes mellitus is complex, as the present case illustrates. Management of metforminassociated lactic acidosis by. Our results partially contradict a large cohort study investigating the association between metformin use and acidosis at low egfr. 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. 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. However, the information available in patients with moderatesevere chronic kidney disease is scarce.
Metforminassociated lactic acidosis mala is a potentially fatal condition characterized by an elevation in serum lactate in patients with metformin exposure. Metforminassociated 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. 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. In the last 14 years, we observed a significant increase in hospitalizations for mala to our center. Metformin is the first choice drug in type ii diabetes. Patient on metformin develops an acute lifethreatening illness e. In 1998, the results of the uk prospective diabetes study indicated that metformin treatment is associated with a reduction in total mortality compared to other antihyperglycaemic treatments. Pdf metformin is an oral antidiabetic drug that is widely used alone or in combination with other drugs with type 2 diabetes mellitus. Metforminassociated lactic acidosis mala is one such rare, lifethreatening adverse drug effect. More recently it has also been used to improve fertility and weight reduction in patients with polycystic ovary syndrome. However, the best treatment strategy remains a matter of debate.
These patients presented with severe circulatory shock due to lactic acidosis. Lactic acidosis associated with metformin in patients with. A comprehensive literature search performed by salpeter et al. 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. In certain conditions lactic acidosis mala can occur. We report the case of a 70yearold man with a glycated haemoglobin of 7. Experience with 3 cases of metforminassociated lactic acidosis is reported.
Metformin has been widely used as a firstline agent to treat type 2 diabetes mellitus. Acidosis lactica, en relacion con insuficiencia renal aguda y metformina, tratada con hemodialisis con bicarbonatoa case of lactic acidosis related to acute renal. We report the development of mala in a 67yearold man with diabetes who presented with progressive abdominal pain and bloody diarrhoea. The differential diagnosis at this point should include sepsis, diabetic ketoacidosis, alcoholic ketoacidosis, toxic alcohols, and biguanide metformin toxicity. Most cases of metforminassociated lactic acidosis are from patients who either had abnormal kidney function or overdosed on metformin. In clinical practice, 2294% of patients using metformin have contraindications to metformin. Despite its being generally safe and associated with a reduction of cardiovascular events, diabetesrelated endpoints and overall mortality, metformin may lead to a rare but extremely serious adverse reaction. Although metformin associated lactic acidosis mala is a very rare event, the mortality associated with it is close to 50%. Despite a good safety profile in most patients with diabetes, the risk of metforminassociated lactic acidosis is real if safety guidelines are ignored. Metformin associated lactic acidosis mala remains rare, but potentially fatal condition. Metformin was used in canadians without contraindications for 56,000 patientyears without any reported cases of lactic acidosis. Acute and chronic use of metformin can lead to rare complication of metforminassociate lactic acidosis mala excreted unmetabolized in proximal tubules.
Metformin use and metforminassociated lactic acidosis in. Metforminassociated lactic acidosis mimicking ischaemic. Association of metformin use with risk of lactic acidosis across the range of kidney function. 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.
Treatment consists of vital function support and drug. Lactic acidosis is a form of metabolic acidosis that begins in the kidneys. Lactic acidosis in metformintreated diabetes mellitus patients is a very rare complication, with a high mortality rate and is often associated with an underlying. Association of metformin use with risk of lactic acidosis. Continuous renal replacement therapy for the treatment of metformin associated lactic acidosis has been documented in some case. 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 may have potentiated. Dec 17, 2019 metformin has been widely used as a firstline agent to treat type 2 diabetes mellitus. Nevertheless, this has been a controversial matter. The onset of metforminassociated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain.
Although the reported incidence of mala is rare, the product labeling for metformin states that the drug is contraindicated in patients with risk factors for lactic acidosis. Metformin associated lactic acidosis is more likely to occur in. Introduction metformin is a first line oral medication for diabetes mellitus shown to decrease cardiovascular morbidity and mortality. Although its use is controversial, intermittent hemodialysis is reported to be the most frequently used treatment in conjunction with nonspecific supportive measures. 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. 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. Metformin is the firstline therapy for the treatment of diabetes mellitus. Risk factors include renal insufficiency, higher doses of metformin, and alcoholism. Treatment of the lactic acidosis induced by metformin is based on the use of supportive general measures.
Metforminassociated lactic acidosis mala is a rare but potentially lifethreatening adverse effect of metformin use in patients with type 2 diabetes, the risk for which is increased in patients with acute kidney injury. This drug has a renal excretion and its use requires caution in a. Metformin is the most commonly prescribed oral antidiabetic agent. Metformininduced implies the absence of another cause of lactic acidosis which was not the case here. Older patients with type 2 diabetes are prone to developing adverse events with aggressive antihyperglycaemic therapy. 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. Oral route tablet postmarketing cases of metforminassociated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias.
He had a history of type 2 diabetes mellitus, and his medications included regular metformin. Metforminassociated lactic acidosis journal of the american. The phantom of lactic acidosis due to metformin in. The strong association of lactic acidosis with phenformin use resulted in a reluctance on the part of. Efficacy of metformin in patients with noninsulindependent diabetes mellitus. 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 phantom of lactic acidosis due to metformin in patients. Pharmacokinetic data suggest that the risk of metforminassociated lactic acidosis mala may be increased after rouxeny gastric bypass rygb surgery. While this particular patients presentation is likely multifactorial, she also has metforminassociated lactic acidosis mala, secondary to metformin use during renal failure. Lactic acidosis in a patient with type 2 diabetes mellitus. Background metformin associated lactic acidosis mala is a severe metabolic failure with high related mortality.
Metforminassociated lactic acidosis is more likely to occur in. The reported incidence of metformin associated lactic acidosis mala in type 2 diabetes mellitus dm is 39 cases per 100 000 patient. Despite dose adjustment for renal failure, diabetic patients with chronic kidney disease ckd stage iiiiv are at risk for rapid decline in renal function by whatever reason, so that mf. Defronzo ra, goodman am, multicenter metformin study group. In 1995, the oral antihyperglycemic agent, metformin, was introduced in the united states for treating diabetes mellitus. The most common symptoms following overdose include vomiting, diarrhea, abdominal pain, tachycardia, drowsiness, and, rarely, hypoglycemia or hyperglycemia. Unlimited viewing of the articlechapter pdf and any associated supplements and figures. A prognostic and therapeutic study metformin associated lactic acidosis is a rare and serious complication of biguanide treatment.
There were 59 cases of metforminassociated lactic acidosis mortality rate of 25. Outcome of severe lactic acidosis associated with metformin. Sir, metformin is an oral antihyperglycaemic agent used in the treatment of type 2 diabetes mellitus. Metforminassociated lactic acidosis in type 2 diabetes. We could not identify any predisposing factor for lactic acidosis other than renal. If metforminassociated lactic acidosis is suspected, immediately discontinue prandimet and institute general supportive measures in a hospital setting. Metformin associated lactic acidosis mala is a wellknown serious side effect of biguanides. A prognostic and therapeutic study metforminassociated lactic acidosis is a rare and serious complication of biguanide treatment. Metforminassociated lactic acidosis was the most frequent serious adverse reaction related to metformin reported to the national authority 18. Risk of metforminassociated lactic acidosis mala in. Request pdf metforminassociated lactic acidosis introduction.
Metformin, along with other drugs in the biguanide class, increases plasma lactate levels in a plasma. Continuous renal replacement therapy for the treatment of metforminassociated lactic acidosis has been documented in some case. Metformin is the only biguanide that is available in the u. Though metforminassociated lactic acidosis mala is an extremely rare condition most estimates are. Metforminassociated lactic acidosis in a burn patient. We present two case reports of metforminassociated lactic acidosis. Postmarketing cases of metforminassociated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. Our aim was to report the evolution and outcome of cases managed by continuous renal replacement therapy crrt. Sep 16, 2009 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%. Cureus metforminassociated lactic acidosis successfully. Metforminassociated lactic acidosis is a severe and infrequent adverse event. 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. Also, in a study of diabetic patients presenting to the emergency room, the incidence of lactic acidosis was not higher in patients taking metformin than those given sulfonylureas or insulin. The aim of this study was to examine the impact of metformin on plasma lactate levels before and after rygb surgery.
Metforminassociated lactic acidosis mala is a lifethreatening condition up to 50% mortality is described and its developing rate increases. An 82yearold man with no prior renal history was brought to hospital after being found by his family in a confused state. Lactic acidosis is a rare but serious adverse effect in patients treated with metformin. Reports of a high incidence of lactic acidosis associated with the use of an earlier biguanide, phenformin 1. In 306 cases, sufficient documentation was available to establish the diagnosis with reasonable certainty blood lactate, 6 meqlitre or greater, and blood ph, 7. Postoperative lactic acidosis in patients receiving metformin. Therefore, it presents a diagnostic challenge that is critical to identify, particularly in patients with renal impairment at baseline.
It is also used in the treatment of polycystic ovary syndrome. Metforminassociated lactic acidosis was the most frequent. 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. Metforminassociated lactic acidosis refractory to hemodialysis in the. Role of metformin accumulation in metforminassociated lactic acidosis. Lactic acidosis in patients on metformin therapy can be referred to as metformininduced or metforminassociated. Metformin mf accumulation during acute kidney injury is associated with high anion gap lactic acidosis type b mfassociated lactic acidosis, mala, a serious medical condition leading to high mortality. Apr 11, 2019 metformin associated lactic acidosis mala definition. Risk of metforminassociated lactic acidosis mala is reported to be an estimated 6. We report the outcomes of our clinical and therapeutic approach. 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. These and other results led to its progressive widespread use. Metformin associated lactic acidosis mala is one such rare, lifethreatening adverse drug effect.
A unique case of metforminassociated lactic acidosis. Dec 20, 2014 metformin is the recommended firstline therapy for most patients with type 2 diabetes mellitus t2dm. Though the prevalence of metforminassociated lactic acidosis mala is low, mortality is high, ranging from 2550%. There are many possible causes of lactic acidosis, and in any given patient, several causes may coexist. Metformin toxicity is driven by suppression of hepatic gluconeogenesis, and interference with oxidative phosphorylation, resulting in the formation of lactate from pyruvate 2. Lactic acidosis is a rare 1 but serious complication of metformin therapy with a high fatality rate 2. Metformin is a safe drug when correctly used in properly selected patients. In addition to its glucoselowering properties, it also reduces allcause mortality through its antiinflammatory and cardioprotective effects. In clinical practice, 2294% of patients using metformin have contraindications to metformin, so the incidence of mala may be higher than reported. Metforminassociated lactic acidosis in sweden 19771991. Patients with mala will have a low ph, a highanion gap metabolic acidosis and high lactate levels. 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. In patients with shortness of breath and clear lungs, consider metabolic acidosis with respiratory alkalis as a potential cause. Data reveal that the incidence of mla is less than 5.
268 1580 720 22 170 481 346 54 215 362 1436 1258 6 343 669 1324 433 21 1215 734 495 1467 1398 1657 70 673 257 654 1499 69 1196 1622 633 1481 1357 1055 1528 692 863 403 1119 967 814 1472