Impact of Metformin Use on Lactate Kinetics in Patients with Severe Sepsis and Septic Shock

Park, Joong-Min; Hwang, Sung Yeon; Jo, Ik Joon; Jeon, Kyeongman; Suh, Gee Young; Lee, Tae Rim; Yoon, Hee; Chul, Won; Sim, Min Seob; Carrière, Keumhee C.; Yeon, Seungmin; Shin, Tae Gun

doi:10.1097/shk.0000000000000782

Cited by 38 publications

(44 citation statements)

References 31 publications

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“…The acidification is due to proton accumulation rather than lactate accumulation. Lastly, it should be noted that sepsis does not alter lactate kinetics in metformin‐treated patients …”

Section: The Relationship Between Metformin and Lactic Acidosis/a Phymentioning

confidence: 98%

Metformin‐associated lactic acidosis (MALA): Moving towards a new paradigm

Lalau

Kajbaf

Protti

et al. 2017

Diabetes Obesity Metabolism

107

113

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Although metformin has been used for over 60 years, the balance between the drug's beneficial and adverse effects is still subject to debate. Following an analysis of how cases of so-called "metformin-associated lactic acidosis" (MALA) are reported in the literature, the present article reviews the pitfalls to be avoided when assessing the purported association between metformin and lactic acidosis. By starting from pathophysiological considerations, we propose a new paradigm for lactic acidosis in metformin-treated patients. Metformin therapy does not necessarily induce metformin accumulation, just as metformin accumulation does not necessarily induce hyperlactatemia, and hyperlactatemia does not necessarily induce lactic acidosis. In contrast to the conventional view, MALA probably accounts for a smaller proportion of cases than either metformin-unrelated lactic acidosis or metformin-induced lactic acidosis. Lastly, this review highlights the need for substantial improvements in the reporting of cases of lactic acidosis in metformin-treated patients. Accordingly, we propose a check-list as a guide to clinical practice.

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“…The acidification is due to proton accumulation rather than lactate accumulation. Lastly, it should be noted that sepsis does not alter lactate kinetics in metformin‐treated patients …”

Section: The Relationship Between Metformin and Lactic Acidosis/a Phymentioning

confidence: 98%

Metformin‐associated lactic acidosis (MALA): Moving towards a new paradigm

Lalau

Kajbaf

Protti

et al. 2017

Diabetes Obesity Metabolism

107

113

View full text Add to dashboard Cite

show abstract

“…26 Other studies show no differences in the clearance and normalization (over 24 h) of serum lactate between sepsis patients on chronic metformin therapy and those who have not taken metformin. 31 In light of these findings, an expansion of metformin's role in sepsis may be expected. FIGURE 1 Effect of metformin in tuberculosis patients with diabetes mellitus as comorbidity.…”

Section: Sepsis Metformin and Lactatementioning

confidence: 99%

“…In fact, some studies show a lower mortality risk in sepsis patients on chronic metformin therapy compared to those not on the therapy . Other studies show no differences in the clearance and normalization (over 24 h) of serum lactate between sepsis patients on chronic metformin therapy and those who have not taken metformin . In light of these findings, an expansion of metformin's role in sepsis may be expected.…”

Section: Sepsismentioning

confidence: 99%

Is metformin poised for a second career as an antimicrobial?

Malik

Mehdi

Ali

et al. 2018

Diabetes Metabolism Res

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Metformin, a widely used antihyperglycaemic, has a good safety profile, reasonably manageable side-effects, is inexpensive, and causes a desirable amount of weight loss. In 4 studies of patients with tuberculosis (1 prospective and 3 retrospective), metformin administration resulted in better outcomes. In mice with several models of endotoxemia, metformin diminished levels of proinflammatory cytokines and improved survival. Laboratory studies showed effectiveness of the drug on multiple pathogens, including Trichinella spiralis, Staphylococcus aureus, Pseudomonas aeruginosa, hepatitis B virus, hepatitis C virus, and human immunodeficiency virus. Metformin administration in humans and mice produced major changes in the composition of the gut microbiota. These recently discovered microbe-modulating properties of the drug have led investigators to predict wide therapeutic utility for metformin. The recent easing in United States Food and Drug Administration (FDA) guidelines regarding administration of metformin to patients with kidney disease, and reduced anxiety about patient safety in terms of lactic acidosis, increase the probability of broadening of metformin's usage as a treatment of infectious agents. In this text we review articles pertinent to metformin's effects on microorganisms, both pathogens and commensals. We highlight the possible role of metformin in a wide range of infectious diseases and a possible expansion of its therapeutic profile in this field. A systematic review was done of PubMed indexed articles that examined the effects of metformin on a wide range of pathogens. Metformin was found to have efficacy as an antimicrobial agent in patients with tuberculosis. Mice infected with Trypanosomiasis cruzi had higher survival when also treated with metformin. The drug in vitro was active against T. spiralis, S. aureus, P. aeruginosa, and hepatitis B virus. In addition there is emerging literature on its role in sepsis. We conclude that metformin may have a potential role in the therapy for multiple infectious diseases. Metformin, in addition to its traditional effects on glucose metabolism, provides anti-microbial benefits in patients with tuberculosis and in a very wide range of other infections encounters in vitro and in vivo.

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“…However, recent studies indicate that patents with prior use of metformin have shown nearly 30% increase survival despite high level of lactate [108]. Notably, while lactate is among well-established predictors of sepsis, recent clinical trials have shown that decrease in lactate production had no effects on sepsis survival [109110].…”

Section: Extension Of Metabolic Profile To Diagnose Outcome Of Sepsismentioning

confidence: 99%

Mitochondrial Dysfunction and Immune Cell Metabolism in Sepsis

Park

Żmijewski

2017

Infect Chemother

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Sepsis is a life threatening condition mediated by systemic infection, but also triggered by hemorrhage and trauma. These are significant causes of organ injury implicated in morbidity and mortality, as well as post-sepsis complications associated with dysfunction of innate and adaptive immunity. The role of cellular bioenergetics and loss of metabolic plasticity of immune cells is increasingly emerging in the pathogenesis of sepsis. This review describes mitochondrial biology and metabolic alterations of immune cells due to sepsis, as well as indicates plausible therapeutic opportunities.

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Impact of Metformin Use on Lactate Kinetics in Patients with Severe Sepsis and Septic Shock

Abstract: Lactate levels in metformin users were initially elevated in the early phase of resuscitation from severe sepsis and septic shock. However, there was no significant difference in lactate levels, LC, and normalization over the initial 24 h period based on metformin use.

Cited by 38 publications

References 31 publications

Metformin‐associated lactic acidosis (MALA): Moving towards a new paradigm

Metformin‐associated lactic acidosis (MALA): Moving towards a new paradigm

Is metformin poised for a second career as an antimicrobial?

Mitochondrial Dysfunction and Immune Cell Metabolism in Sepsis

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