The Association between Metformin Therapy and Lactic Acidosis

Kuan, Isabelle H. S.; Savage, Ruth; Duffull, Stephen B.; Walker, Robert; Wright, Daniel F. B.

doi:10.1007/s40264-019-00854-x

Cited by 29 publications

(20 citation statements)

References 234 publications

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“…This retrospective cohort study shows a lower but not statistically different mortality in MALA patients treated with ECTR compared to those who were not. The overall mortality of 40% in our study is in line with the mortality reported in previous studies, ranging from 20 to 50% [7,8,[12][13][14][17][18][19][20][21]. Blood pH, lactate, creatinine, and serum metformin concentration in the ECTR group in this study are similar to that reported in the literature [9,13,[20][21][22].…”

Section: Discussionsupporting

confidence: 91%

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Extracorporeal treatment of metforminassociated lactic acidosis in clinical practice: a retrospective cohort study

Laar

Vermeij

Elsen-Hutten

et al. 2020

Eur J Clin Pharmacol

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Purpose To assess whether extracorporeal treatment (ECTR) improves outcome of patients with metformin-associated lactic acidosis (MALA) and to evaluate the clinical applicability of the Extracorporeal Treatments in Poisoning Workgroup (EXTRIP) criteria for starting ECTR in metformin poisoning. Methods Patients with metformin serum concentrations above 2 mg/l who were admitted in the Deventer Teaching Hospital between January 2000 and July 2019 and complied with the definition of MALA (pH < 7.35 and lactate concentration > 5 mmol/ l) were included. Mortality and clinical parameters of patients treated with ECTR or not were compared. In addition, treatment of MALA in clinical practice was verified against the criteria of EXTRIP. Results Forty-two patients were included. Lactate (13.8 versus 10.5 mmol/l, p = 0.01), creatinine (575 versus 254 umol/l, p < 0.01)), metformin (29.4 versus 8.6 mg/l, p < 0.01) concentrations, and vasopressor requirement (72% versus 23%, p < 0.01) were significantly higher in the ECTR-group. Blood pH (7.05 versus 7.19, p = 0.03) and bicarbonate (6 versus 11 mmol/l, p < 0.01) were significantly lower. Mortality, length of hospital stay, and mechanical ventilation requirement were not statistically different. In 83% of patients, treatment of MALA was in accordance with the EXTRIP criteria. Conclusions Although there was no statistical benefit in mortality shown from ECTR, ECTR might be lifesaving in MALA, considering the ECTR-group was significantly sicker than the non-ECTR-group. The majority of patients were treated in line with the EXTRIP criteria. Severity of lactic acidosis and renal impairment were the main indications for initiating ECTR.

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Section: Discussionsupporting

confidence: 91%

“…accelerated lactate production and reduced lactate metabolism [1,[3][4][5]]. There appears to be a clear relationship between metformin accumulation and lactic acidosis, although some authors have pointed out that several such patients had other confounding risk factors for lactic acidosis [3][4][5]7].…”

Section: Introductionmentioning

confidence: 99%

Extracorporeal treatment of metforminassociated lactic acidosis in clinical practice: a retrospective cohort study

Laar

Vermeij

Elsen-Hutten

et al. 2020

Eur J Clin Pharmacol

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“…96 Although there is still debate regarding transport of the drug into/out of cancer cells that would support a direct effect of metformin, these doses exceed those achievable in women, largely due to life-threatening toxicities. 97 Additional studies point towards important effects of lowering systemic glucose and insulin levels, as well as estrogen production in the breast adipose. 93,98,99 Most studies implicate activation of the metabolic sensor AMP-activated protein kinase (AMPK).…”

Section: Can the Treatment Of Endocrinopathies Reduce Recurrence Overmentioning

confidence: 99%

Endocrine Therapy-related Endocrinopathies—Biology, Prevalence, and Implications for the Management of Breast Cancer

Brown

Andreopoulou

2020

Oncology &Amp; Hematology Review (US)

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“…Metformin is the initial drug treatment for adults with type 2 diabetes mellitus (DM2) but has been associated with lactic acidosis (LA), a very rare and life-threatening adverse event, especially in patients with renal disease [1,2]. The safety evidence supporting its use in these patients remains controversial and scarce.…”

Section: Introductionmentioning

confidence: 99%

Lactic acidosis associated with metformin in diabetic patients with chronic kidney disease: a multicentre case-control study using electronic health records

Ávila

Videla

Gómez-Lumbreras

et al. 2020

Preprint

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Background Several studies have assessed the risk of lactic acidosis with metformin use. However, data of this association in patients with renal impairment are still scarce and controversial. Our aim was therefore to assess the association between metformin and lactic acidosis in Spanish type 2 diabetic patients with chronic kidney disease. Methods A case-control study (ALIMAR-C2) was performed using the electronic health records from hospitals linked to their corresponding primary healthcare regions. The cases were adult (≥ 18 years) diabetic patients with chronic kidney disease, admitted to seven Spanish hospitals from 2010 to 2016. Ten controls (≥ 18 years, diabetic patients with chronic kidney disease) per case were selected from the population within the same primary healthcare region of the hospital cases. The patients’ hospital health records were linked to their corresponding primary healthcare information. Analyses included multivariable logistic regression and adjustment for potential confounders. Results Our study included 126 cases and 1,260 matched controls. The current use of metformin and administration at high doses (> 2 g) were associated with lactic acidosis (adjusted OR: 1.92, 95% CI: 1.21–3.03; OR: 3.13, 95% CI: 1.63–6.01, respectively). The estimated case fatality rate was 46.8% (95% CI: 38.3–55.5%). An increased risk of lactic acidosis was observed in patients with mild to moderate renal impairment (OR: 3.41, 95% CI: 1.48–7.85). As an unexpected finding, diuretic drugs use was also associated with lactic acidosis (OR: 2.73, 95% CI: 1.67–4.46). Conclusions Metformin was associated with an increased risk of lactic acidosis in patients with type 2 diabetes mellitus and chronic kidney disease. New data is needed to confirm the association between diuretic drugs and lactic acidosis in this group of patients.

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The Association between Metformin Therapy and Lactic Acidosis

Cited by 29 publications

References 234 publications

Extracorporeal treatment of metforminassociated lactic acidosis in clinical practice: a retrospective cohort study

Extracorporeal treatment of metforminassociated lactic acidosis in clinical practice: a retrospective cohort study

Endocrine Therapy-related Endocrinopathies—Biology, Prevalence, and Implications for the Management of Breast Cancer

Lactic acidosis associated with metformin in diabetic patients with chronic kidney disease: a multicentre case-control study using electronic health records

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