title: Incidence of lactic acidosis in patients with type 2 diabetes with and without renal impairment treated with metformin: a retrospective cohort study.
abstract: OBJECTIVE
  To determine whether the use of metformin in type 2 diabetic patients with various kidney functions is associated with an increased risk of lactic acidosis (LA).
  
  
  METHODS
  This study was a retrospective analysis of U.K. patient records from the Clinical Practice Research Datalink database from 1 January 2007 to 31 December 2012. Inclusion criteria were 1) diagnosis of type 2 diabetes before 1 January 2007, 2) treatment with metformin, and 3) at least one assessment of renal function between 2007 and 2012. Renal function was assessed by glomerular filtration rate and categorized as normal (N), mildly reduced (Mi), moderately reduced (Mo), or severely reduced (Se) function. The outcome of the study was LA.
  
  
  RESULTS
  A total of 77,601 patients treated with metformin for type 2 diabetes were identified. There were 35 LA events (10.37 [95% CI 7.22-14.42] per 100,000 patient-years) of which none were fatal and 23 were linked to a comorbidity. No significant difference in the incidence of LA was observed across N, Mi, Mo and Se renal function groups (7.6 [0.9-27.5], 4.6 [2.00-9.15], 17 [10.89-25.79], and 39 [4.72-140.89] cases per 100,000 patient-years, respectively).
  
  
  CONCLUSIONS
  The overall LA incidence rate for patients on metformin in this study was within the range of rates reported in the literature for patients with type 2 diabetes, and no significant difference was observed among patients with N, Mi, Mo, and Se function.
authors.affiliation: Global Drug Safety Epidemiology, Merck KGaA, Darmstadt, Germany florent-frederic.richy@merckgroup.com.
authors.forename: Florent F
authors.initials: FF
authors.lastname: Richy
authors.affiliation: Global Drug Safety Epidemiology, Merck KGaA, Darmstadt, Germany.
authors.forename: Meritxell
authors.initials: M
authors.lastname: Sabidó-Espin
authors.affiliation: Global Drug Safety Epidemiology, Merck KGaA, Darmstadt, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Guedes
authors.affiliation: Genesis Research Group, Hoboken, NJ.
authors.forename: Frank A
authors.initials: FA
authors.lastname: Corvino
authors.affiliation: Global Medical Affairs, Merck KGaA, Darmstadt, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Gottwald-Hostalek
mesh_terms: D000140:Acidosis, Lactic / Q000139:chemically induced / Q000453:epidemiology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016208:Databases, Factual; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000453:epidemiology*; D003928:Diabetic Nephropathies / Q000150:complications / Q000453:epidemiology*; 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; D012189:Retrospective Studies; D006113:United Kingdom / Q000453:epidemiology; D055815:Young Adult
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin