Objective: To examine the risk of colorectal cancer after orlistat initiation in the UK population.
Design: Retrospective matched cohort study.
Setting: Data from the UK Clinical Practice Research Datalink from September 1998 to December 2008.
Participants: 33,625 adults aged 18 years or over who started treatment with orlistat; each orlistat initiator was matched to up to five non-initiators (n=160,347) on age, sex, body mass index, and calendar time.
Main outcome measures: Associations between orlistat initiation and the risk of colorectal cancer, assessed by calculating hazard ratios with propensity score adjusted Cox proportional hazard models.
Results: Of 193,972 patients with a median age of 47 (interquartile range 37-57) years, 77% were women and approximately 90% were obese (body mass index ≥ 30). Orlistat initiators were more likely to have a previous history of diabetes or hypertension and to receive prescriptions for anti-diabetes drugs, statins, and aspirin compared with non-initiators. In the intention to treat analysis, 57 colorectal cancer events were identified among orlistat initiators and 246 among non-initiators, with median follow-up times of 2.96 and 2.86 years, respectively. The calculated incidence rate of colorectal cancer per 100,000 person years was 53 (95% confidence interval 41 to 69) for orlistat initiators and 50 (44 to 57) for non-initiators. Orlistat initiation was not associated with a higher risk of colorectal cancer (adjusted hazard ratio 1.11, 95% confidence interval 0.84 to 1.47). Findings were robust in the as treated analyses and in patients who were aged 50 years or over, were morbidly obese, or had a history of diabetes.
Conclusions: This study found no evidence of an increased risk of colorectal cancer after the initiation of orlistat. It is limited by the relatively short follow-up time, and the possibility of adverse effects of long term orlistat use on risk of colorectal cancer cannot be excluded.