title: Impact of Japanese regulatory action on metformin-associated lactic acidosis in type II diabetes patients.
abstract: BACKGROUND
  The March 2012 regulatory action issued by the Japanese government signalled the rare but serious complication of lactic acidosis that can occur during metformin treatment, especially with the high dose formulation, h-metformin, and in those above 75 years old.
  
  
  OBJECTIVE
  To assess quantitatively the impact of this regulatory action on patient management using a medical information database (MID).
  
  
  METHODS
  Eight hospitals in Japan.
  
  
  METHODS
  Using a commercial MID, we collected data on adult outpatients treated with metformin, including h-metformin, during a 2-year study period between April 1, 2011 and March 31, 2013. The 2-year study period spanned 1 year before and after the regulatory action. The frequencies of lactate measurement in all metformin users, h-metformin users, and new users (started on metformin during the study period) were compared between the periods before and after the regulatory action, using generalized estimating equations. Trends in metformin prescription for elderly patients were analysed month-wise by regression analysis using an interrupted time series design.
  
  
  METHODS
  The rate ratios (RR) of lactate testing before and after the regulatory action.
  
  
  RESULTS
  Of 4347 metformin users, 784 patients were >75 years old. A significant increase in lactate measurement was observed after the regulatory action than before in the overall study population, with an adjusted RR of 2.14 (95 % confidence interval 1.24-3.68). No significant change was found in h-metformin users and new users because lactate measurements were being performed as frequently in these subgroups before the regulatory action. There were no meaningful changes in the proportion of elderly metformin users in the overall population.
  
  
  CONCLUSIONS
  The regulatory action led to increased lactate measurement in the overall metformin users, but did not affect metformin prescription rate in the elderly patients. Our findings probably reflect the doctors' judgement that the benefits of metformin use outweigh the risk of lactic acidosis if lactate testing is performed regularly.
authors.affiliation: Division of Medicinal Safety Science, National Institute of Health Sciences, Kamiyoga 1-18-1, Setagaya-ku, Tokyo, 158-8501, Japan.
authors.forename: Tadaaki
authors.initials: T
authors.lastname: Hanatani
authors.forename: Kimie
authors.initials: K
authors.lastname: Sai
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tohkin
authors.forename: Katsunori
authors.initials: K
authors.lastname: Segawa
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Saito
mesh_terms: D000140:Acidosis, Lactic / Q000097:blood / Q000139:chemically induced* / Q000453:epidemiology*; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D003625:Data Collection; D016208:Databases, Factual; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D004335:Drug and Narcotic Control; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects; D007564:Japan / Q000453:epidemiology; D019344:Lactic Acid / Q000097:blood; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000009:adverse effects*; D008875:Middle Aged; D010818:Practice Patterns, Physicians' / Q000706:statistics & numerical data*; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D007004:Hypoglycemic Agents; D019344:Lactic Acid; D008687:Metformin
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