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Orlistat and the risk of acute liver injury: self controlled case series study in UK Clinical Practice Research Datalink

BMJ 2013; 346 doi: (Published 12 April 2013) Cite this as: BMJ 2013;346:f1936
  1. Ian J Douglas, lecturer in pharmacoepidemiology,
  2. Julia Langham, lecturer,
  3. Krishnan Bhaskaran, lecturer in statistical epidemiology,
  4. Ruth Brauer, research student,
  5. Liam Smeeth, professor of clinical epidemiology
  1. 1Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK
  1. Correspondence to: I Douglas ian.douglas{at}
  • Accepted 8 March 2013


Objective To measure the association between orlistat and acute liver injury.

Design Self controlled case series study.

Setting Population based primary care setting, United Kingdom.

Participants 94 695 patients receiving orlistat and registered in the UK Clinical Practice Research Datalink and linked with Hospital Episode Statistics data between 1999 and 2011.

Main outcome measure Relative incidence of acute liver injury comparing periods when patients were receiving orlistat with periods of non-usage.

Results Among 94 695 patients who received orlistat, 988 cases of acute liver injury were identified, with 335 confirmed as definite cases and 653 as probable cases. For all cases an increased incidence of liver injury was detected during the 90 day period before orlistat was first started, with an incidence rate ratio of 1.50 (95% confidence interval 1.10 to 2.06). The incidence remained raised during the first 30 days of treatment (2.21, 1.43 to 3.42), before returning to baseline levels with prolonged treatment. When the risk during the first 90 days of treatment was compared with the 90 days preceding first treatment, the incidence of liver injury was not increased (1.02, 0.67 to 1.56). An analysis restricted to definite cases showed no evidence of an increased risk of liver injury during treatment.

Conclusion The incidence of acute liver injury was higher in the periods both immediately before and immediately after the start of orlistat treatment. This suggests that the observed increased risks of liver injury linked to the start of treatment may reflect changes in health status associated with the decision to begin treatment rather than any causal effect of the drug.


  • Contributors: IJD conceived and designed the study, analysed the data, interpreted the results, and cowrote the paper. JL and RB analysed the data, interpreted the results, and cowrote the paper. KB and LS designed the study, interpreted the results, and cowrote the paper. IJD acts as guarantor.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at (available from the corresponding author) and declare: IJD is funded by a Medical Research Council methodology fellowship, KB is funded by a National Institute for Health Research postdoctoral fellowship, and LS is funded by a Wellcome Trust fellowship; IJD holds stock in GlaxoSmithKline and consults for GlaxoSmithKline, Takeda, and Gilead on topics not related to orlistat; LS consults for GlaxoSmithKline on topics not related to orlistat; and no other relationships or activities that could appear to have influenced the submitted work. The funders played no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.

  • Ethical approval: This study was approved by the independent scientific advisory committee for Medicines and Healthcare products Regulatory Agency database research and the London School of Hygiene and Tropical Medicine ethics committee.

  • Data sharing: No additional data available.

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:

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