Document Detail

Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus.
MedLine Citation:
PMID:  20393934     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Metformin is an oral anti-hyperglycemic agent that has been shown to reduce total mortality compared to other anti-hyperglycemic agents, in the treatment of type 2 diabetes mellitus. Metformin, however, is thought to increase the risk of lactic acidosis, and has been considered to be contraindicated in many chronic hypoxemic conditions that may be associated with lactic acidosis, such as cardiovascular, renal, hepatic and pulmonary disease, and advancing age.
OBJECTIVES: To assess the incidence of fatal and nonfatal lactic acidosis, and to evaluate blood lactate levels, for those on metformin treatment compared to placebo or non-metformin therapies.
SEARCH STRATEGY: A comprehensive search was performed of electronic databases to identify studies of metformin treatment. The search was augmented by scanning references of identified articles, and by contacting principal investigators.
SELECTION CRITERIA: Prospective trials and observational cohort studies in patients with type 2 diabetes of least one month duration were included if they evaluated metformin, alone or in combination with other treatments, compared to placebo or any other glucose-lowering therapy.
DATA COLLECTION AND ANALYSIS: The incidence of fatal and nonfatal lactic acidosis was recorded as cases per patient-years, for metformin treatment and for non-metformin treatments. The upper limit for the true incidence of cases was calculated using Poisson statistics. In a second analysis lactate levels were measured as a net change from baseline or as mean treatment values (basal and stimulated by food or exercise) for treatment and comparison groups. The pooled results were recorded as a weighted mean difference (WMD) in mmol/L, using the fixed-effect model for continuous data.
MAIN RESULTS: Pooled data from 347 comparative trials and cohort studies revealed no cases of fatal or nonfatal lactic acidosis in 70,490 patient-years of metformin use or in 55,451 patients-years in the non-metformin group. Using Poisson statistics the upper limit for the true incidence of lactic acidosis per 100,000 patient-years was 4.3 cases in the metformin group and 5.4 cases in the non-metformin group. There was no difference in lactate levels, either as mean treatment levels or as a net change from baseline, for metformin compared to non-metformin therapies.
AUTHORS' CONCLUSIONS: There is no evidence from prospective comparative trials or from observational cohort studies that metformin is associated with an increased risk of lactic acidosis, or with increased levels of lactate, compared to other anti-hyperglycemic treatments.
Shelley R Salpeter; Elizabeth Greyber; Gary A Pasternak; Edwin E Salpeter
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Publication Detail:
Type:  Journal Article; Review     Date:  2010-04-14
Journal Detail:
Title:  The Cochrane database of systematic reviews     Volume:  -     ISSN:  1469-493X     ISO Abbreviation:  Cochrane Database Syst Rev     Publication Date:  2010  
Date Detail:
Created Date:  2010-04-15     Completed Date:  2010-05-21     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  100909747     Medline TA:  Cochrane Database Syst Rev     Country:  England    
Other Details:
Languages:  eng     Pagination:  CD002967     Citation Subset:  IM    
Medicine, Stanford University, and Santa Clara Valley Medical Center, 2400 Moorpark Ave, Suite 118, San Jose, CA, USA, 95128.
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MeSH Terms
Acidosis, Lactic / chemically induced*,  mortality
Cohort Studies
Diabetes Mellitus, Type 2 / drug therapy*
Hypoglycemic Agents / adverse effects*,  contraindications
Lactic Acid / blood
Metformin / adverse effects*,  contraindications
Prospective Studies
Reg. No./Substance:
0/Hypoglycemic Agents; 50-21-5/Lactic Acid; 657-24-9/Metformin
Update Of:
Cochrane Database Syst Rev. 2010;(1):CD002967   [PMID:  20091535 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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