title: Epidemiology of lactic acidosis in type 2 diabetes patients with metformin in Japan.
abstract: To estimate the incidence of lactic acidosis (LA) and role of metformin in Japanese patients with type 2 diabetes mellitus (T2DM) treated with anti-diabetes drugs.
  
  
  
  This retrospective propensity score matched cohort study was conducted using the Japanese Medical Data Vision claims database. T2DM patients aged 18 or above who received diabetes drugs during January 2010 through August 2014 were identified. Cases of LA were identified based on reimbursement codes and confirmed by lactic acid test and subsequent treatment by hemodialysis or intravenous sodium bicarbonate. Poisson regression and Cox proportional hazard models were used to estimate the incidence and assess if metformin use was associated with increased risk of LA.
  
  
  
  Thirty cases of LA were identified among 283 491 treated T2DM patients with 504 169 patient-years of follow-up. Crude incidence of LA was 5.95 per 100 000 patient-years. T2DM patients with chronic kidney disease (CKD) were seven-fold more likely to develop LA than those without CKD (adjusted hazard ratio (aHR), 7.33, 95%CI, 3.17-16.96). Use of metformin was not associated with risk of LA in the study population (aHR, 0.92, 95%CI, 0.33-2.55), and in the propensity score matched cohort (aHR, 0.90, 95%CI, 0.26-3.11). Similar findings were observed among diabetes patients with chronic liver disease (CLD) and CKD. The age-sex adjusted incidence rates in metformin users and non-users were 5.80 and 5.78 per 100 000 person-years, respectively (Incidence rate ratio, 1.00, p = 0.99).
  
  
  
  This study found that use of metformin was not associated with increased risk of LA in diabetic patients including those with CKD or CLD. © 2016 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.
authors.affiliation: Takeda Development Center Japan, Takeda Pharmaceutical Company Limited, Osaka, Japan. chia-hsien.chang@takeda.com.
authors.forename: Chia-Hsien
authors.initials: CH
authors.lastname: Chang
authors.affiliation: Takeda Development Center Japan, Takeda Pharmaceutical Company Limited, Osaka, Japan.
authors.forename: Motonobu
authors.initials: M
authors.lastname: Sakaguchi
authors.affiliation: Takeda Development Centre Europe Ltd, London, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Dolin
mesh_terms: D000140:Acidosis, Lactic / Q000453:epidemiology* / Q000209:etiology; D000293:Adolescent; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D016208:Databases, Factual; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015994:Incidence; D007564:Japan; D008107:Liver Diseases / Q000150:complications; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D016012:Poisson Distribution; D057216:Propensity Score; D016016:Proportional Hazards Models; D051436:Renal Insufficiency, Chronic / Q000150:complications; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin
keywords: Japan; MDV database; lactic acidosis; metformin; pharmacoepidemiology