Metformin‐associated lactic acidosis: a rare or very rare clinical entity?

Chan, N N; Brain, H; Feher, Michael

doi:10.1046/j.1464-5491.1999.00006.x

Cited by 119 publications

(87 citation statements)

References 107 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Butformin was withdrawn from the market in 1978 because it promoted lactic acidosis. 19 Metformin mainly inhibits hepatic glucose release, gluconeogenesis, and b-oxidation of fatty acids. Metformin inhibits respiration when incubated with isolated mitochondria or isolated complex I protein in a time-and dose-dependent manner.…”

Section: Assay Validation Using Marketed Drugsmentioning

confidence: 99%

Measuring Interference of Drug-Like Molecules with the Respiratory Chain: Toward the Early Identification of Mitochondrial Uncouplers in Lead Finding

Stock

Matter

Diekert³

et al. 2013

ASSAY and Drug Development Technologies

View full text Add to dashboard Cite

The electron transport chain (ETC) couples electron transfer between donors and acceptors with proton transport across the inner mitochondrial membrane. The resulting electrochemical proton gradient is used to generate chemical energy in the form of adenosine triphosphate (ATP). Proton transfer is based on the activity of complex I-V proteins in the ETC. The overall electrical activity of these proteins can be measured by proton transfer using Solid Supported Membrane technology. We tested the activity of complexes I, III, and V in a combined assay, called oxidative phosphorylation assay (oxphos assay), by activating each complex with the corresponding substrate. The oxphos assay was used to test in-house substances from different projects and several drugs currently available on the market that have reported effects on mitochondrial functions. The resulting data were compared to the influence of the respective compounds on mitochondria as determined by oxygen consumption and to data generated with an ATP depletion assay. The comparison shows that the oxidative phosphorylation assay provides both a rapid approach for detecting interaction of compounds with respiratory chain proteins and information on their mode of interaction. Therefore, the oxphos assay is a useful tool to support structure activity relationship studies by allowing early identification of mitotoxicity and for analyzing the outcome of phenotypic screens that are susceptible to the generation of mitotoxicity-related artifacts.

show abstract

Section: Assay Validation Using Marketed Drugsmentioning

confidence: 99%

Measuring Interference of Drug-Like Molecules with the Respiratory Chain: Toward the Early Identification of Mitochondrial Uncouplers in Lead Finding

Stock

Matter

Diekert³

et al. 2013

ASSAY and Drug Development Technologies

View full text Add to dashboard Cite

show abstract

“…In the 70,490 patient-years of the pooled metformin group, there were no cases of fatal or non-fatal lactic acidosis found [7]. Moreover, according to Chan et al [8], the low prevalence of metforminassociated lactic acidosis was comparable to the prevalence of sulfonylurea-induced hypoglycemia; metformin had many benefits for management of type II diabetes mellitus, assuming that recommended guidelines for metformin use were adhered to [8]. Lalau et al [9] also performed a literature search on the link between metformin and lactic acidosis in metformin therapy; and there was no true metformin-associated lactic acidosis and no mortalities due to metformin alone were found.…”

Section: Discussionmentioning

confidence: 84%

A Case of Hyperosmolar Hyperglycemic State Caused by Ischemic Pancreatitis

Leung¹,

Murdock²,

Lustig³

et al. 2014

Int J Biomed

View full text Add to dashboard Cite

Background: The hyperosmolar hyperglycemic state (HHS) is a dangerous complication that can arise with diabetes mellitus. Emergent treatment is necessary to reinstate hemodynamic stability, as mortality rates for HHS are exceptionally high and can have multiple complications.Case Report: A 42-year-old female presented unresponsive to the emergency department. Upon arrival, the patient's examination was consistent with hypovolemia and tachycardia. Review of systems included a one-week history of nausea and vomiting. The patient had stopped all of her medications one year prior, only restarting metformin one week prior to admission. Her presenting systolic blood pressure was 119 mmHg before she developed respiratory failure secondary to a poor mental state. The presenting blood sugar level was 1263 mg/dL, and ketones were not detected in her urine. The patient recovered from her HHS and was discharged in a stable condition.Conclusion: This case study postulates that the patient's excessive nausea and vomiting led to pancreatitis secondary to ischemia, which induced a HHS. This is important because hyperglycemia superimposed on any ischemic insult can increase the risk of multiorgan failure, as with our patient. Thus, recognition and management of resulting complications needs to be emergent.

show abstract

“…Metforminassociated lactic acidosis (MALA) is actually rare, with an estimated incidence of 3-10 per 100,000 person-years. [36] Of note, the risk of developing lactic acidosis from metformin has been calculated to be 20 times less frequent than with phenformin [37]. Other risk factors for MALA include states that result in increased lactate production, such as sepsis, cardiogenic shock and alcoholism.…”

Section: Non-glycaemic Effectsmentioning

confidence: 99%