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

Abstract

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.

Metformin toxicity in the intensive care unit: A case series and review of the literature

“…[ 25 ] Not surprisingly, an observational study of 105 patients with MALA reported that a lower APACHE II score and time to dialysis (<6 h) are associated with lower 30-day mortality. [ 26 ]…”

An Analysis of Clinical Outcomes of Exploratory Pediatric Metformin Ingestions Reported to the Texas Poison Center Network From 2011 to 2021

“…Metformin associated lactic acidosis can occur at therapeutic doses in adults or in overdose, and it usually occurs in older patients with acute kidney injury or chronic kidney disease, with dehydration, and sepsis. 14 , 15 It is rarely reported in children.…”

Clinical efficacy and cost‐effectiveness of metformin in different patient populations: A narrative review of real‐world evidence

“…59 Lactic acidosis and dialysis treatment within 6 h after admission were independently associated with lower 30-day mortality. 60 Unexpectedly, some evidence suggests that mortality for lactic acidosis is not predicted by metformin dose or levels, 61 and may be even reduced in subjects consuming higher metformin doses. 62 The ALIMAR-C2 study, announced in 2019, should assess the association between metformin use and lactic acidosis in PwD and impaired kidney function through the evaluation of health records from eight Spanish hospitals linked to their corresponding primary care health areas, comprising approximately 22.1 million person-years of followup.…”

“…In metformin‐treated PwD admitted in an emergency context, a plasma metformin concentration ≥ 9.9 mg/L was strongly associated with lactic acidosis 59 . Lactic acidosis and dialysis treatment within 6 h after admission were independently associated with lower 30‐day mortality 60 . Unexpectedly, some evidence suggests that mortality for lactic acidosis is not predicted by metformin dose or levels, 61 and may be even reduced in subjects consuming higher metformin doses 62 .…”