Common side effects of orlistat are gastrointestinal, such as selleck screening library abdominal pain or oily stool, potentially leading to diagnostic endoscopies. This could lead to an earlier diagnosis of (asymptomatic) colorectal cancer, resulting in an increased hazard ratio, but cannot explain our finding; on the other hand, endoscopies also could lead to early removal of colonic adenomatous polyps, resulting in a reduced long term risk of colorectal cancer, but we would expect such a beneficial effect to take several years to become apparent. We also examined the frequency of patients who underwent screening for colorectal cancer within one year after cohort entry and found no difference between orlistat initiator and non-initiators cohorts (0.37% v 0.38%).
The generalizability of the results is also limited by the lack of information on race/ethnicity in the CPRD. Conclusions Our study provides no evidence of an increased risk of colorectal cancer after starting orlistat treatment in UK adults. The study is limited by the relatively short follow-up time, and we cannot exclude the possibility of adverse effects of long term orlistat use on risk of colorectal cancer. What is already known on this topic Orlistat is one of the most widely used anti-obesity drugs and is the only over the counter drug for weight loss approved in the United States and Europe An animal study showed that orlistat may induce aberrant crypt foci in rodents, but data from population based post-marketing studies on the risk of colorectal cancer are lacking What this study adds This study in the UK population showed no evidence of an increased risk of colorectal cancer associated with use of orlistat The study 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 Notes We thank Pascal Egger for help with data management.
Contributors: J-LH, TS, RSS, and CRM conceived and designed the study. TS oversaw the conduct of the study. CRM and SSJ provided the data and oversaw the database programming. J-LH did the data analysis. J-LH and TS interpreted the results and drafted the manuscript. TS, RSS, CRM, and SSJ contributed to critical revision of the manuscript for important intellectual content. All authors approved the final manuscript. TS is the guarantor.
Funding: The study was funded by the population research award from the Lineberger Comprehensive Cancer Center (LCCC) at the University of North Carolina at Chapel Hill and R01 “type”:”entrez-nucleotide”,”attrs”:”text”:”AG023178″,”term_id”:”7681353″,”term_text”:”AG023178″AG023178 GSK-3 from the National Institute of Aging at the National Institutes of Health. The funding agencies had no role in the design of the study; in the analysis and interpretation of the data; in the writing of the report; or in the decision to submit the paper for publication.