Metformin is a widely used oralantidiabetic with positive effects on metabolism. However, it is associated with a 5060% mortality rate. Supportive care and maintenance of hydration and renal function are the mainstays of management. Lactic acidosis associated with metformin treatment is a rare but important adverse event, and unravelling the problem is critical.
Lactic acidosis cases often occurs in intensive care units. However, the information available in patients with moderatesevere chronic kidney disease is scarce. Metformin induced lactic acidosis what is the effective. The onset of metforminassociated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. It is an established firstline agent for treatment of incident type 2 diabetes mellitus 1, given that it lowers blood glucose without hypoglycemia or weight gain and is available in inexpensive generic fomulations. Postoperative lactic acidosis in patients receiving metformin. In the last 14 years, we observed a significant increase in hospitalizations for mala to our center. Metformin induced lactic acidosis is rare and usually other causative factors are present. Lactic acidosis associated with metformin in patients with moderate to severe chronic kidney disease. The use of metformin in patients with type 2 diabetes mellitus has been associated with lactic acidosis. Phenformin, the relatively toxic predecessor of the metformin, exhibited antithiamine activity in laboratory animals.
Metforminassociated lactic acidosis is more likely to occur. Metformin associated lactic acidosis presenting as an ischemic gut in a. This consideration is especially important in patients with severe anion gaps associated with lactic acidosis out of proportion to the patients clinical presentation. In this article we highlight how high lactate levels are not an accurate predictor of mortality in deliberate metformin overdose. A purely isolated metformin induced type b lactic acidosis most likely only occurs in the setting of medication overdose or renal failure.
When metformin is administered orally, approximately 40% of the dose is absorbed. Controversy remains whether the use of metformin is a cause or a coincidence. 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. The onset of metformin associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. What is the risk of metformin associated lactic acidosis. Lactic acidosis is a serious complication acodosis metformin therapy and is more frequent in patients with kidney failure and other intercurrent complaints. The major toxicity from acute or chronic biguanide use is lactic acidosis. However, your risk for developing lactic acidosis might be much higher, depending on whether you have other risk factors for lactic. Metformin associated lactic acidosis in a burn patient. Lactic acidosis is a serious complication of metformin therapy and is more frequent in patients with kidney failure and other intercurrent complaints. Lactic acidosis is also a consequence of the processes causing rigor mortis.
Metformin induced lactic acidosis mala is a serious illness which should identify and treat urgently. Summary metformin may increase your risk of lactic acidosis. In type b lactic acidosis produced by medication, withdrawal of the medication may be necessary to resolve the lactic acidosis. Lactic acidosis almost never occurs with metformin exposure during routine medical care. 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. The term metformininduced lactic acidosis refers to cases that cannot be explained by any major risk factor other than drug.
When metformin is implicated as the cause of lactic acidosis, metformin plasma levels 5 mcgml are generally found. In the medical literature, haemodialysis is recommended as the treatment of choice in. Metformininduced lactic acidosis in the absence of chronic renal impairment. Metformin is known to be an effective treatment for patients with type 2 diabetes mellitus. A decrease to subnormal levels of previously normal serum b12 levels has been reported in approximately 7% of patients treated with metformin during controlled clinical trials. Metforminassociated lactic acidosis mala is a potentially fatal condition characterized by an elevation in serum lactate in patients with. It usually occurs when a precipitating disease induces an acute renal failure and an incidental. We present a case of metforminassociated lactic acidosis mala, which resulted in cardiopulmonary arrest. Astrazeneca pharmaceuticals lp xigduo xr dapagliflozin. Recent letters call attention to the tendency of metformin to interfere with vitamin b12 function. The findings in our study show that the metabolic acidosis is a lactic acidosis. Although the decrease is generally welltolerated and rarely.
Metformin is an effective and widely used antihyperglycemic agent. Metformin associated lactic acidosis was characterized by elevated blood lactate levels 5 mmolliter, anion gap acidosis without evidence of ketonuria or. 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. Prognosis is not related to serum metformin level, it is the patients comorbidity that seems to predict survival 14. The estimated mortality of metformininduced lactic acidosis is about 50% 1. However, the best treatment strategy remains a matter of debate. Metformininduced lactic acidosis with emphasis on the anion gap. Metformin inhibits hepatic gluconeogenesis from lactate, pyruvate, alanine, resulting in additional lactate and substrate for lactate production. Pdf outcome of severe lactic acidosis associated with. 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.
Some have suggested that the link between metformin and lactic acidosis is coincidental rather than causal. Metformin was also taken off the us market due to concerns over lactic acidosis, but it subsequently has been proven safe and. We had established that the donor cardiac function was excellent. Metformin is the principal biguanide in clinical use. 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. Metformin is a safe drug when correctly used in properly selected patients. The benefit of metformin on diabetes complications and mortality in t2dm is well established. Metformininduced lactic acidosis with emphasis on the. Lactic acidosis is a rare problem that happens when oxygen levels in your body drop.
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. Food and drug administration fda has given metformin a special warning, called a black box warning, about lactic acidosis. Pearlman bl, fenves az, emmett m metforminassociated lactic acidosis. If you have any possible lactic acidosis symptoms, contact your healthcare provider immediately. Metformin is a biguanide, a drug class of herbal origin that has been widely used to treat diabetes since the 1950s. Lactic acidosis is an uncommon side effect of metformin use, which is more likely to arise in patients with certain predisposing factors. Impact of metformin exposure before icu stay remains controversial. 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. Toxicity management metformin od does not usually cause hypoglycaemia manage airway, breathing and circulation in standard manner metformin associated lactic acidosis mala. 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. Metforminassociated lactic acidosis was characterized by elevated blood lactate levels 5 mmolliter, anion gap acidosis without evidence of ketonuria or.
We report the outcomes of our clinical and therapeutic approach. Dont use this drug if you already have lactic acidosis. Very rarely, metformin can cause a lifethreatening side effect called lactic acidosis. Taking metformin may increase your risk of lactic acidosis. Lactic acidosis is characterized by elevated blood lactate levels 5 mmoll, decreased blood ph, electrolyte disturbances with an increased anion gap, and an increased lactate pyruvate ratio. The lactic acidosis from metformin is primarily type b. Diabetes increases the risk of developing lactic acidosis. Among 18 patients with acute pulmonary edema due to left ventricular failure, 14 had a blood ph of less than 7. Metformin associated lactic acidosis is a severe and potentially fatal condition that can be easily avoided. Introduction metformin is the most commonly prescribed oral antihyperglycemic agent in the treatment of type 2 diabetes dm2 1.
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. Metforminassociated lactic acidosis was characterized by elevated blood lactate levels 5 mmoll, anion gap acidosis without evidence of ketonuria or. Metformin in 2019 clinical pharmacy and pharmacology. Lactic acidosis ketoacidosis due to uncontrolled diabetes mellitus, excess alcohol intake, or fasting ingestions o methanol or ethylene glycol. Risk of fatal and nonfatal lactic acidosis with metformin. Heart transplant complicated by metformin induced lactic. 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.
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. 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 therapy and lactic acidosis risk overview. A unique case of metforminassociated lactic acidosis hindawi. 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. Treatment of the lactic acidosis induced by metformin is based on the use of supportive general measures. There have been reports of lactic acidosis in people who take metformin, which is a standard noninsulin medication for treating type 2 diabetes mellitus. In real life, however, associated lactic acidosis has been repeatedly, although rarely, reported. Lactic acidosis may develop in people with type 1 and 2 diabetes mellitus, especially if their diabetes is not well controlled. Metformin is an oral antihyperglycemic agent used to treat patients with type ii diabetes mellitus. Metformin may interfere with vitamin b12 cyanocobalamin absorption from the b12intrinsic factor complex. Metforminassociated lactic acidosis is a rare and serious complication of biguanide treatment.
Metformin is thought to induce lactic acidosis and haemodynamic instability but may reduce icu mortality. The patients known chronic kidney disease, potentially exacerbated by cardiopulmonary bypass, likely contributed to metformin induced lactic acidosis. 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. Metformin associated lactic acidosis mala is a wellknown serious side effect of biguanides. Does metformin exposure before icu stay have any impact on. Metformin is associated with severe lactic acidosis. However, we found similar results when only adjusting for baseline egfr in active comparator analyses. No warranty is given about the accuracy of the copy. In such pactica, when the body needs more energy than usual, for example during exercise or disease, mitochondria cannot match the cells demand for atp, and lactic acidosis results. Ukpds34 lactic acidosis in patients with severe ckd is likely mediated by accumulation of excessive levels of metformin, which is renally.
The most significant adverse effect of metformin therapy is the development of metforminassociated lactic acidosis in the susceptible patient. Metformin is the first line agent in the treatment of type 2. Metformin associated lactic acidosis presenting as an ischemic gut in a patient who then survived a cardiac arrest. Due to the unpredictable nature of heart transplant, our patient received metformin within 48 hours of surgery. 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. 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. In an overdose, the lactic acidosis can be compounded by type a when the drugs lactic acid accumulation leads to cardiovascular collapse, tissue hypoperfusion, and hepatic dysfunction. Lactic acidosis associated with metformin in patients with. Association of metformin use with risk of lactic acidosis. Metformin is a commonly used treatment modality in type 2 diabetes mellitus, with a well documented side effect of lactic acidosis. In the intensive care setting lactate and ph levels are regularly used as a useful predictor of poor prognosis. Treatment of metformin intoxication complicated by lactic acidosis.
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