Mortality rate in so-called “metformin-associated lactic acidosis”: a review of the data since the 1960s

Kajbaf, F.; Lalau, Jean–Daniel

doi:10.1002/pds.3689

Cited by 63 publications

(47 citation statements)

References 22 publications

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“…Metformin is rarely the sole cause of LA and even the prognosis seems better in LA occurring in the presence of metformin [37]. Even the overall mortality rate for MALA was down to 25% in a recent review by Kajbaf and Lalau as compared with around 50% during the period 1966–2000 [38]. After the widespread adoption of various formulas for the measurement of estimated GFR, the nephrology community has come to regard the use of serum Cr in isolation as irrelevant for the assessment of renal function.…”

Section: Resultsmentioning

confidence: 99%

Changes in metformin use in chronic kidney disease

Imam

2017

Clinical Kidney Journal

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Metformin is one of the oldest and most widely prescribed antidiabetic medicines worldwide. It is the only such medicine that has shown a reduction of cardiovascular mortality in diabetes mellitus type 2. Since many diabetic patients have chronic kidney disease, its use is often curtailed by practitioners due to fear of lactic acidosis and the US Food and Drug Administration (FDA) warnings that, until recently, had been in place for decades. Current guidelines, though somewhat vague regarding dosages, clearly pave the way for spreading the use of metformin in patients with lower glomerular filtration rates. These guidelines also suggest moving away from just looking at serum creatinine to create a cut-off. Metformin’s costs are lower, and in many underdeveloped countries this is the only medicine available for poor patients. More widespread use of metformin will further help with health care costs, as well as obesity. It will simplify the use of diabetes mellitus type 2 management with lower incidences of hypoglycemia. With all the mounting evidence, the FDA is finally requiring labeling changes regarding recommendations, to allow the use of metformin in patients with much reduced kidney function.

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Section: Resultsmentioning

confidence: 99%

Changes in metformin use in chronic kidney disease

Imam

2017

Clinical Kidney Journal

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“…Publication bias is a critical concern in this study as severe cases with unexpected favorable outcomes may be more likely reported by clinicians and accepted by medical journals. We compared the mortality rate of selected MALA patients between 1995 and 2010 with those from a pharmacovigilence database covering the same time span and the results were not too different (17.7% vs. 25%) [30]. The much lower mortality in our study population compared to the historical series may reflect the efficient support role of the RRT in maintaining the acid-base homeostasis in MALA [18, 31].…”

Section: Discussionmentioning

confidence: 99%

Serum lactate level and mortality in metformin-associated lactic acidosis requiring renal replacement therapy: a systematic review of case reports and case series

et al. 2017

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BackgroundThe current practice concerning timing, mode, and dose of renal replacement therapy (RRT) in patients with metformin-associated lactic acidosis (MALA) with renal failure remains unknown. To investigate whether serum lactate level and prescription pattern of RRT are associated with mortality in patients with MALA requiring RRT.MethodsWe searched PubMed/Medline and EMBASE from inception to Sep 2014 and applied predetermined exclusion criteria. Case-level data including case’s demographics and clinical information related to MALA were abstracted. Multiple logistic regression modeling was used to examine the predictors of mortality.ResultsA total of 253 unique cases were identified with cumulative mortality of 17.2%. Eighty-seven percent of patients had acute kidney injury. Serum lactate level was significantly higher in non-survivors (median 22.5 mmol/L) than in survivors (17.0 mmol/L, p-value <0.01) and so did the median blood metformin concentrations (58.5 vs. 43.9 mg/L, p-value = 0.05). The survival advantage was not significantly different between the modalities of RRT. The adjusted odds ratio of mortality for every one mmol/L increase in serum lactate level was 1.09 (95% CI 1.02–1.17, p-value = 0.01). The dose-response curve indicated a lactate threshold greater than 20 mmol/L was significantly associated with mortality.ConclusionsOur study suggests that predialysis level of serum lactate level is an important marker of mortality in MALA patients requiring RRT with a linear dose-response relationship. To better evaluate the optimal prescription of RRT in MALA, we recommend fostering an international consortium to support prospective research and large-scale standardized case collection.Electronic supplementary materialThe online version of this article (doi:10.1186/s12882-017-0640-4) contains supplementary material, which is available to authorized users.

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“…However, metforminassociated lactic acidosis occurs with a low incidence [13], but the patients suffering from this acidosis have a high mortality risk [14,15]. Although metformin has been reported to cross the blood-brain barrier and was found accumulated in the cerebrospinal fluid [16], only little is known about the effects of metformin on brain cell metabolism.…”

Section: Introductionmentioning

confidence: 98%

The Antidiabetic Drug Metformin Stimulates Glycolytic Lactate Production in Cultured Primary Rat Astrocytes

2015

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Metformin is the most frequently used drug for the treatment of type 2 diabetes in humans. However, only little is known about effects of metformin on brain metabolism. To investigate potential metabolic consequences of an exposure of brain cells to metformin, we incubated rat astrocyte-rich primary cultures with this compound. Metformin in concentrations of up to 30 mM did not acutely compromise the viability of astrocytes, but caused a time- and concentration-dependent increase in cellular glucose consumption and lactate production. For acute incubations in the hour range, the presence of 10 mM metformin doubled the glycolytic flux, while already 1 mM metformin doubled glycolytic flux during incubation for 24 h. In addition to metformin, also other guanidino compounds increased astrocytic lactate production. After 4 h of incubation, half-maximal stimulation of glycolysis was observed for metformin, guanidine and phenformin at concentrations of around 3 mM, 3 mM and 30 µM, respectively. The acute stimulation of glycolytic lactate production by metformin was persistent after removal of extracellular metformin and was also observed, if glucose was absent from the incubation medium or replaced by other hexoses. The metformin-induced stimulation of glycolytic flux was not prevented by compound C, an inhibitor of AMP-dependent protein kinase, nor was it additive to the stimulation of glycolytic flux caused by respiratory chain inhibitors. These data demonstrate that the antidiabetic drug metformin has the potential to strongly activate glycolytic lactate production in brain astrocytes.

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Mortality rate in so-called “metformin-associated lactic acidosis”: a review of the data since the 1960s

Abstract: The overall mortality rate for MALA was around 50% during the period 1960-2000 but has since fallen to around 25%.

Cited by 63 publications

References 22 publications

Changes in metformin use in chronic kidney disease

Changes in metformin use in chronic kidney disease

Serum lactate level and mortality in metformin-associated lactic acidosis requiring renal replacement therapy: a systematic review of case reports and case series

The Antidiabetic Drug Metformin Stimulates Glycolytic Lactate Production in Cultured Primary Rat Astrocytes

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