title: Metformin use and risk of lactic acidosis in people with diabetes with and without renal impairment: a cohort study in Denmark and the UK.
abstract: To assess risk of lactic acidosis among metformin users compared with other glucose-lowering agent users, according to renal function.
  
  
  
  Using routine registries and databases, we conducted a cohort study. Of 43 580 metformin and 37 788 other glucose-lowering agent users in northern Denmark and 102 688 metformin and 28 788 other glucose-lowering agent users in the UK during 2001-2011, we identified lactic acidosis using diagnostic codes. We calculated the incidence rates of lactic acidosis in metformin and other glucose-lowering agent users overall and according to baseline estimated GFR (eGFR) levels.
  
  
  
  In Denmark, the incidence rates of lactic acidosis were 11.6 (95% CI 7.0-18.1) and 1.8 (95% CI 0.4-5.4) per 100 000 person-years of metformin use and of other glucose-lowering agent use, respectively. In the UK, the corresponding lactic acidosis incidence rates were 6.8 (95% CI 4.6-9.6) and 1.0 (95% CI 0.01-5.7) per 100 000 person-years of metformin use and of other glucose-lowering agent use. The incidence rates increased with decreasing baseline eGFR in both countries. Of the metformin-exposed people with lactic acidosis, 37% in Denmark and 34% in the UK experienced a decline in renal function in the year before the diagnosis.
  
  
  
  Risk of lactic acidosis was higher in metformin users than in other glucose-lowering agent users, and increased with decreasing eGFR, although this could be attributable to surveillance bias; however, diagnosed lactic acidosis was rare and can occur regardless of renal function.
authors: Boston Collaborative Drug Surveillance Program, Boston University School of Public Health, Lexington, MA, USA.
authors: L
authors: L
authors: Li
authors: Boston Collaborative Drug Surveillance Program, Boston University School of Public Health, Lexington, MA, USA.
authors: S
authors: S
authors: Jick
authors: Boston Collaborative Drug Surveillance Program, Boston University School of Public Health, Lexington, MA, USA.
authors: C
authors: C
authors: Gopalakrishnan
authors: Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, Denmark.
authors: U
authors: U
authors: Heide-Jørgensen
authors: Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, Denmark.
authors: H
authors: H
authors: Nørrelund
authors: Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, Denmark.
authors: H T
authors: HT
authors: Sørensen
authors: Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, Denmark.
authors: C F
authors: CF
authors: Christiansen
authors: Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, Denmark.
authors: V
authors: V
authors: Ehrenstein
mesh_terms: D000140:Acidosis, Lactic / Q000453:epidemiology*; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015331:Cohort Studies; D016208:Databases, Factual; D003718:Denmark / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D015994:Incidence; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D051437:Renal Insufficiency / Q000453:epidemiology* / Q000378:metabolism; D012307:Risk Factors; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin