Document Detail

Metformin and lactic acidosis: cause or coincidence? A review of case reports.
MedLine Citation:
PMID:  14746555     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Metformin has been associated with the serious side-effect lactic acidosis. However, it remains unclear whether the use of metformin was a cause or a coincidence in lactic acidosis. DESIGN: A literature search of the Index Medicus (1959-66) and of the databases Embase, Medline, Medline Express (1966-99) was performed using the keywords metformin, biguanides and lactic acidosis. All articles of cases with metformin-induced lactic acidosis (MILA) were cross-referenced. SUBJECTS: Cases were included for analysis if they met the following criteria: serum pH < or =7.35, lactate concentration > or =5 mmol L(-1). INTERVENTION: A forum of six experts in intensive care medicine independently categorized the cases in MILA unlikely (score 0), possible MILA (score 1) or probable MILA (score 2). MAIN OUTCOME MEASURES: Statistical analysis included the paired interobserver agreement (kappa) and multivariate regression analysis. RESULTS: Of 80 reported cases, 33 were excluded because of insufficient quality. The forum scores of the remaining 47 cases were distributed normally with a mean score of 7 (range 2-10). The kappa-value was 0.041 (SD = 0.24, range -0.514, 0.427). Neither lactate concentration nor mortality correlated with serum metformin concentrations. CONCLUSIONS: Given the low interobserver agreement and the lack of any relationship between metformin levels and outcome parameters, the concept that there is a simple, causal relationship between metformin use and lactic acidosis in diabetic patients has to be reconsidered.
A M E Stades; J T Heikens; D W Erkelens; F Holleman; J B L Hoekstra
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Journal of internal medicine     Volume:  255     ISSN:  0954-6820     ISO Abbreviation:  J. Intern. Med.     Publication Date:  2004 Feb 
Date Detail:
Created Date:  2004-01-28     Completed Date:  2004-03-01     Revised Date:  2005-11-16    
Medline Journal Info:
Nlm Unique ID:  8904841     Medline TA:  J Intern Med     Country:  England    
Other Details:
Languages:  eng     Pagination:  179-87     Citation Subset:  IM    
Department of Internal Medicine, Diakonessenhuis, Utrecht, The Netherlands.
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MeSH Terms
Acidosis, Lactic / chemically induced*
Aged, 80 and over
Diabetes Mellitus, Type 2 / drug therapy
Hypoglycemic Agents / adverse effects*
Medical Records
Metformin / adverse effects*
Middle Aged
Regression Analysis
Risk Factors
Reg. No./Substance:
0/Hypoglycemic Agents; 657-24-9/Metformin

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