Setting Data from the UK Clinical Practice selleck chemical Cabozantinib Research Datalink from September 1998 to December 2008. Participants 33625 adults aged 18 years or over who started treatment with orlistat; each orlistat initiator was matched to up to five non-initiators (n=160347) 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 193972 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 100000 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. Introduction Orlistat is an anti-obesity drug that reduces the absorption of dietary fat by inhibiting lipase and is currently approved for both prescription (Xenical, Roche) and over the counter (Alli, GlaxoSmithKline) sale in the United States and Europe. Long term treatment with orlistat has been shown to significantly reduce weight and waist circumference and to have beneficial effects on blood pressure, lipids, and type 2 diabetes.1 2 3 4 5 An animal study found that orlistat was associated with a significant increase in the number of colonic aberrant crypt foci, independent of high fat diet.

6 This result is supported by another preclinical study, which showed that orlistat induced colonic cell proliferation and severe crypt alternation.7 Brefeldin_A Aberrant crypt foci are putative precursors of colon cancer, although controversy has arisen about aberrant crypt foci as a biomarker of colorectal cancer.8 9 10 An analysis of pooled clinical trials conducted by orlistat manufactures found no statistically significant difference in risk of colorectal cancer between orlistat and placebo groups.