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Orlistat and the Risk of Acute Liver Injury: Self Controlled Case Series Study in UK Clinical Practice Research Datalink


Orlistat and the Risk of Acute Liver Injury: Self Controlled Case Series Study in UK Clinical Practice Research Datalink

Ian J Douglas et al. BMJ.


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.

Conflict of interest statement

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.


Fig 1 Typical timeline for patient in study. *Liver injury could occur at any point during observation period
Fig 2 Flow of participants through study

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