Do Patients Die with or from Metformin-Associated Lactic Acidosis (MALA)? Systematic Review and Meta-analysis of pH and Lactate as Predictors of Mortality in MALA

Blumenberg, Adam; Benabbas, Roshanak; Sinert, Richard; Jeng, Amy; Wiener, Sage W.

doi:10.1007/s13181-019-00755-6

Cited by 32 publications

(20 citation statements)

References 31 publications

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“…On the contrary to the effect of plasma metformin levels, how serum lactate levels results in mortality was still controversial [ 24 ]. Similarly to our study, the recent meta-analysis [ 26 ] which resembled in serum lactate level showed lactate was not a good discriminating index between survivors and non-survivors. Besides metformin and lactate removal, dialysis also improved numerous physiologic factors, allowing patients for a rapid recovery [ 27 ].…”

Section: Discussionsupporting

confidence: 76%

Metformin-associated lactic acidosis and factors associated with 30-day mortality

Thammavaranucupt

Phonyangnok²,

Parapiboon

et al. 2022

PLoS ONE

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Background Metformin-associated lactic acidosis (MALA) is a rare event but underrecognition may lead to unfavorable outcomes in type 2 diabetes patients. While many risk factors of MALA have been identified, how to reduce mortality from MALA is a matter of debate. This study aimed to explore the factors associated with 30-day mortality amongst MALA patients. Methods An observational study enrolled patients diagnosed with MALA between January 2014 and December 2017. MALA was defined by a history of metformin administration, metabolic acidosis (arterial blood gas pH <7.35 or HCO3 <15 mmol/L), and elevated plasma lactate level (>5 mmol/L). We examined risk factors including age, sex, underlying diseases, current medications, blood tests, disease severity, and dialysis data. Mortality status was identified from medical records or report on telephone. Results We included 105 MALA patients. Most patients (95.2%) were diagnosed acute kidney injury stage 3 according to KDIGO 2012 definition. The 30-day mortality rate was 36.2% and dialysis rate was 85.7%. The survivors had higher proportions of underlying chronic kidney disease, presence of metabolic acidosis, receiving renal replacement therapy within 6 hours, and haemodialysis, whereas the non-survivors had higher percentage of hypertension and disease severity. Lower APACHE II score (HR = 0.95; 95%CI, 0.91–0.99; p = 0.038), time to dialysis < 6 hours (0.31; 0.14–0.69; 0.004), and haemodialysis (0.20;0.06–0.67; 0.010) were associated with lower 30-day mortality, using multivariate Cox-regression analysis. Conclusions Mortality rate amongst patients with MALA was high. Early dialysis treatment within 6 hours after admission and haemodialysis were independently associated with lower 30-day mortality. The large scale, well-designed studies need to confirm these encouraging results.

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Section: Discussionsupporting

confidence: 76%

Metformin-associated lactic acidosis and factors associated with 30-day mortality

Thammavaranucupt

Phonyangnok²,

Parapiboon

et al. 2022

PLoS ONE

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“…MALA exhibit many life-threatening comorbidities such as sepsis and kidney injury that lead to devastating outcomes [39]. In our patient, COVID-19 precipitated the acute renal impairment, further facilitating the incidence of MALA.…”

Section: Discussionmentioning

confidence: 69%

“…The symptoms of MALA include hypotension, altered mental status preceded by gastrointestinal complaints such as diarrhea, nausea, and vomiting [37]. The values of lactate and pH are not prognostic factors whereas the coexistence of sepsis or renal failure is believed to be related to unfavorable outcomes [39]. Measurement of metformin levels is not required for the diagnosis and management, therefore they are not routinely ordered as in our case.…”

Section: Discussionmentioning

confidence: 91%

Metformin-associated lactic acidosis and acute kidney injury in the era of COVID-19

Vordoni

Theofilis

Vlachopanos

et al. 2021

Front Biosci (Schol Ed)

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“…We read with interest the recent systematic review of metformin-associated lactic acidosis (MALA) [1]. While the prognostic utility of nadir pH and peak serum lactate concentration for death appeared poor, we agree with the authors' statements that these results were likely affected by "misidentification of MALA for another disease process and vice versa, confounding by selection and reporting bias, and treatment intensity."…”

mentioning

confidence: 56%

The Effect of Residual Confoundingon Mortality in Metformin-Associated Lactic Acidosis

Wang¹,

Hoffman²

2020

J. Med. Toxicol.

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Do Patients Die with or from Metformin-Associated Lactic Acidosis (MALA)? Systematic Review and Meta-analysis of pH and Lactate as Predictors of Mortality in MALA

Cited by 32 publications

References 31 publications

Metformin-associated lactic acidosis and factors associated with 30-day mortality

Metformin-associated lactic acidosis and factors associated with 30-day mortality

Metformin-associated lactic acidosis and acute kidney injury in the era of COVID-19

The Effect of Residual Confoundingon Mortality in Metformin-Associated Lactic Acidosis

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