title: Association between Metformin Use and Risk of Lactic Acidosis or Elevated Lactate Concentration in Type 2 Diabetes.
abstract: OBJECTIVE
  Metformin can reduce diabetes-related complications and mortality. However, its use is limited because of potential lactic acidosis-associated adverse effects, particularly in renal impairment patients. We aimed to investigate the association of metformin use with lactic acidosis and hyperlactatemia in patients with type 2 diabetes.
  
  
  METHODS
  This was a cross-sectional study from a tertiary university-affiliated medical center. A total of 1954 type 2 diabetes patients were recruited in 2007-2011, and stratified according to the estimated glomerular filtration rate of 60 mL/min/1.73 m². Lactic acidosis was defined as plasma lactate levels >5 mmol/L and arterial pH <7.35.
  
  
  RESULTS
  Metformin was used in 61.4% of the patients with type 2 diabetes mellitus. Plasma lactate levels were not different in the patients with and without metformin use. There was no difference in prevalence of hyperlactatemia and lactic acidosis between the patients with and without metformin use (18.9% vs. 18.7%, p=0.905 for hyperlactatemia and 2.8% vs. 3.3%, p=0.544 for lactic acidosis). Similar results were observed in the patients with estimated glomerular filtration rate <60 mL/min/1.73 m². Most patients with lactic acidosis had at least one condition related to hypoxia or poor tissue perfusion. Multiple regression analysis indicated no association between metformin use and lactic acidosis, whereas tissue hypoxia was an independent risk factor for lactic acidosis [odds ratio 4.603 (95% confidence interval, 1.327-15.965)].
  
  
  CONCLUSIONS
  Metformin use was not associated with hyperlactatemia or lactic acidosis in patients with type 2 diabetes.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Lee
authors.affiliation: Chaum Life Center, CHA University School of Medicine, Seoul, Korea.
authors.forename: Sena
authors.initials: S
authors.lastname: Hwang
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Yong Ho
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Seo Hee
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Dongtan Jeil Women's Hospital, Hwasung, Korea.
authors.forename: Young Mi
authors.initials: YM
authors.lastname: Lee
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hua Pyong
authors.initials: HP
authors.lastname: Kang
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Eugene
authors.initials: E
authors.lastname: Han
authors.affiliation: Department of Laboratory Medicine, Kosin University College of Medicine, Busan, Korea.
authors.forename: Woonhyoung
authors.initials: W
authors.lastname: Lee
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Byung Wan
authors.initials: BW
authors.lastname: Lee
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Eun Seok
authors.initials: ES
authors.lastname: Kang
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Bong Soo
authors.initials: BS
authors.lastname: Cha
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea. endohclee@yuhs.ac.
authors.forename: Hyun Chul
authors.initials: HC
authors.lastname: Lee
mesh_terms: D000140:Acidosis, Lactic / Q000097:blood / Q000139:chemically induced* / Q000453:epidemiology; D000328:Adult; D000368:Aged; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D005260:Female; D006801:Humans; D065906:Hyperlactatemia / Q000097:blood / Q000139:chemically induced* / Q000453:epidemiology; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D015994:Incidence; D019344:Lactic Acid / Q000097:blood; D008297:Male; D008687:Metformin / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D008875:Middle Aged; D015995:Prevalence; D012044:Regression Analysis; D051437:Renal Insufficiency / Q000453:epidemiology / Q000503:physiopathology; D012307:Risk Factors
chemical_list: D007004:Hypoglycemic Agents; D019344:Lactic Acid; D008687:Metformin
keywords: Metformin; diabetes mellitus; lactate; lactic acidosis